Trial Registration
SpeechATAX: Speech treatment in progressive hereditary ataxiaPrinciple Investigators: A/Prof Adam Vogel (PhD), University of Melbourne Prof Matthis Synofzik (MD PhD), Hertie Brain InstituteProf. Alexandra Durr (MD PhD), ICM Institute of the Brain and Spinal CordInvestigators: Prof. Richard Roxburgh (PhD, MD), Auckland UniversityDr. Anna Farrell (PhD), Royal Brisbane and Women’s HospitalLisa Stoll (BSc.), Hertie Brain InstituteMarie Biet, ICM Institute of the Brain and Spinal CordStudy Coordinator:Hannah Reece (BSpPath), University of MelbourneSitesUniversity of Melbourne, Melbourne, AustraliaThe Hertie Institute for Clinical Brain Research, Tübingen, GermanyICM Institute for the Brain and Spinal Cord, Paris, FranceThe Royal Brisbane and Women’s Hospital, Brisbane, AustraliaThe University of Auckland, Auckland, New ZealandTrial RegistrationACTRN12618000519257 Version 1.1Date12th December 2018CONTENTS:PROTOCOL SUMMARYpg. 3INTRODUCTIONpg. 6STUDY DESIGNpg. 9STUDY POPULATIONpg. 10STUDY PROTOCOLpg. 11DETAILS OF INTERVENTION pg.17PARTICIPANT WITHDRAWAL/DISCONTINUATIONpg. 23OUTCOME MEASURES pg. 24STATISTICAL ANALYSISpg. 26SUPPORTING DOCUMENTATION AND OPERATIONALPROCEDURESpg. 27PROTOCOL SUMMARY1.1 PROJECT OVERVIEWTitleSpeechATAX: Speech treatment in progressive hereditary ataxiaStudy Design2-arm wait-list control group parallel design where both groups will receive the therapy. ObjectivesTo investigate the effectiveness of SpeechATAX as a speech therapy for people with progressive hereditary ataxia. PopulationIndividuals 18 years and over with a confirmed genetic diagnosis of progressive hereditary ataxia (specifically Friedreich’s ataxia and Spinocerebellar ataxia type 1, 2, 3 and 6)SitesThe University of Melbourne, Melbourne, AustraliaThe Hertie Institute for Clinical Brain Research, Tübingen, GermanyICM Institute for the Brain and Spinal Cord, Paris, FranceThe Royal Brisbane and Women’s Hospital, Brisbane, AustraliaThe University of Auckland, Auckland, New ZealandStudy INterventionSpeechATAX is a digitized intensive home-based speech therapy treatment. The therapy is based on the principles of neuroplasticity and motor learning, and the exercises are designed to target vocal control, prosody and overall intelligibility of speech. It is completed 5 times per week for 4 weeks and progress is monitored by a speech pathologist. DurationCommenced recruitment June 2018, Anticipated completion of data collection March 2020. Participant DurationGroup A = 3 months from initial assessment to final assessmentGroup B = 4 months from initial assessment to final assessment STUDY SITESSiteAddressContact PersonEmailThe University of Melbourne550 Swanston Street Carlton 3053Adam VogelHannah Reecevogela@unimelb.edu.auHannah.reece@unimelb.edu.auThe Hertie Institute for Clinical Brain ResearchHoppe-Seyler-Str. 3,?D-72076 TübingenMatthis SynofzikLisa Stollmatthis.synofzik@uni-tuebingen.deLisa.Stoll@med.uni-tuebingen.de ICM Institute for the Brain and Spinal Cord47, Boulevard de l'H?pital - CS21414 - 75646 Paris Cedex 13Marie Bietmarie.biet@icm-The University of AucklandAuckland hospital - 2 Park RoadGrafton, Auckland, 1023, New ZealandRichard Roxburgh richard.roxburgh@auckland.ac.nzThe Royal Brisbane and Women’s HospitalRoyal Brisbane and Women’s HospitalHerston Qld 4029Anna Farrellanna.farrell@health..auPROJECT TIMELINE-2439309461500Figure 1: SpeechATAX Study Timetable2. INTRODUCTION2.1 THE PROBLEMThe loss of the ability to speak is a devastating and inevitable outcome of many hereditary ataxias. It results in daily disadvantage, stigmatisation, social marginalisation and underemployment PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkeTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (1-3). Disordered speech is an inevitable consequence of Friedreich ataxia (FRDA) ADDIN EN.CITE <EndNote><Cite><Author>Folker</Author><Year>2010</Year><RecNum>8504</RecNum><DisplayText>(4)</DisplayText><record><rec-number>8504</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="0">8504</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Folker, J.E.</author><author>Murdoch, B.E.</author><author>Cahill, L.M.</author><author>Delatycki, M.B.</author><author>Corben, L.A.</author><author>Vogel, A.P.</author></authors></contributors><titles><title>Dysarthria in Friedreich’s ataxia: a perceptual analysis</title><secondary-title>Folia Phoniatrica et Logopaedia</secondary-title></titles><periodical><full-title>Folia Phoniatrica et Logopaedia</full-title></periodical><pages>97-103</pages><volume>62</volume><number>3</number><dates><year>2010</year></dates><urls></urls></record></Cite></EndNote>(4). There are no known therapies that halt the natural progression of disease ADDIN EN.CITE <EndNote><Cite><Author>Yiu</Author><Year>2015</Year><RecNum>11607</RecNum><DisplayText>(5)</DisplayText><record><rec-number>11607</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1429150432">11607</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yiu, E.M.</author><author>Tai, G.</author><author>Peverill, R.E</author><author>Lee, K.J.</author><author>Croft, K.D.</author><author>Mori, T.A.</author><author>Scheiber-Mojdehkar, B.</author><author>Sturm, B.</author><author>Praschberger, M.</author><author>Vogel, A.P.</author><author>Rance, G.</author><author>Stephenson, S.E.</author><author>Sarsero, J.P.</author><author>Stockley, C.</author><author>Lee, C-Y.J.</author><author>Churchyard, A.</author><author>Evans-Galea, M.V.</author><author>Ryan, M.M.</author><author>Lockhart, P.J.</author><author>Corben, L.A.</author><author>Delatycki, M.B.</author></authors></contributors><titles><title>An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels</title><secondary-title>Journal of Neurology</secondary-title><alt-title>J Neurol</alt-title></titles><periodical><full-title>Journal of Neurology</full-title><abbr-1>J Neurol</abbr-1></periodical><alt-periodical><full-title>Journal of Neurology</full-title><abbr-1>J Neurol</abbr-1></alt-periodical><pages>1-10</pages><keywords><keyword>Friedreich ataxia</keyword><keyword>Clinical trial</keyword><keyword>Resveratrol</keyword><keyword>Oxidative stress</keyword><keyword>Mitochondrial disorder</keyword></keywords><dates><year>2015</year><pub-dates><date>2015/04/07</date></pub-dates></dates><publisher>Springer Berlin Heidelberg</publisher><isbn>0340-5354</isbn><urls><related-urls><url>;(5) or speech disorder (dysarthria) in any neurodegenerative ataxia ADDIN EN.CITE <EndNote><Cite><Author>Vogel</Author><Year>2014</Year><RecNum>11313</RecNum><DisplayText>(6)</DisplayText><record><rec-number>11313</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1399312539">11313</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vogel, A.P.</author><author>Folker, J.E.</author><author>Poole, M.L.</author></authors></contributors><titles><title>Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes</title><secondary-title>Cochrane Database of Systematic Reviews</secondary-title></titles><periodical><full-title>Cochrane Database of Systematic Reviews</full-title></periodical><volume>10</volume><number>CD008953</number><dates><year>2014</year></dates><urls></urls><electronic-resource-num>10.1002/14651858.CD008953.pub2. </electronic-resource-num></record></Cite></EndNote>(6). However, therapy that improves speech is within reach ADDIN EN.CITE <EndNote><Cite><Author>Bislick</Author><Year>2012</Year><RecNum>11836</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11836</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1454642269">11836</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bislick, L.P.</author><author>Weir, P.C.</author><author>Spencer, K.</author><author>Kendall, D.</author><author>Yorkston, K.M.</author></authors></contributors><titles><title>Do principles of motor learning enhance retention and transfer of speech skills? A systematic review</title><secondary-title>Aphasiology</secondary-title></titles><periodical><full-title>Aphasiology</full-title></periodical><pages>709-728</pages><volume>26</volume><number>5</number><dates><year>2012</year><pub-dates><date>2012/05/01</date></pub-dates></dates><publisher>Routledge</publisher><isbn>0268-7038</isbn><urls><related-urls><url>;(7).Our research in speech and ataxia describes the insidious functional decline, loss of ability to carry out basic tasks and diminished quality of life in FRDA PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb2xrZXI8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (9, 10) in neurodegeneration have shown promise for therapies leading to training-induced cognitive and motor learning ADDIN EN.CITE <EndNote><Cite><Author>Cramer</Author><Year>2011</Year><RecNum>11829</RecNum><DisplayText>(11)</DisplayText><record><rec-number>11829</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1454556600">11829</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cramer, S.C.</author><author>Sur, M.</author><author>Dobkin, B.H.</author><author>O'Brien, C.</author><author>Sanger, T.D.</author><author>Trojanowski, J.Q.</author><author>Rumsey, J.M.</author><author>Hicks, R.</author><author>Cameron, J.</author><author>Chen, D.</author><author>Chen, W.G.</author><author>Cohen, L.G.</author><author>deCharms, C.</author><author>Duffy, C. J.</author><author>Eden, G.F.</author><author>Fetz, E.E.</author><author>Filart, R.</author><author>Freund, M.</author><author>Grant, S.J.</author><author>Haber, S.</author><author>Kalivas, P.W.</author><author>Kolb, B.</author><author>Kramer, A.F.</author><author>Lynch, M.</author><author>Mayberg, H.S.</author><author>McQuillen, P.S.</author><author>Nitkin, R.</author><author>Pascual-Leone, A.</author><author>Reuter-Lorenz, P.</author><author>Schiff, N.</author><author>Sharma, A.</author><author>Shekim, L.</author><author>Stryker, M.</author><author>Sullivan, E.V.</author><author>Vinogradov, S.</author></authors></contributors><titles><title>Harnessing neuroplasticity for clinical applications</title><secondary-title>Brain</secondary-title></titles><periodical><full-title>Brain</full-title></periodical><pages>1591-1609</pages><volume>134</volume><number>6</number><dates><year>2011</year><pub-dates><date>2011-06-01 00:00:00</date></pub-dates></dates><urls><related-urls><url>;(11). There are no medical treatments proven to alter disease progression in any common degenerative ataxias. A systematic review by Vogel showed insufficient and low quality evidence from randomised controlled trials or observational studies to determine the effectiveness of any treatment for speech in any hereditary ataxia ADDIN EN.CITE <EndNote><Cite><Author>Vogel</Author><Year>2014</Year><RecNum>11313</RecNum><DisplayText>(6)</DisplayText><record><rec-number>11313</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1399312539">11313</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vogel, A.P.</author><author>Folker, J.E.</author><author>Poole, M.L.</author></authors></contributors><titles><title>Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes</title><secondary-title>Cochrane Database of Systematic Reviews</secondary-title></titles><periodical><full-title>Cochrane Database of Systematic Reviews</full-title></periodical><volume>10</volume><number>CD008953</number><dates><year>2014</year></dates><urls></urls><electronic-resource-num>10.1002/14651858.CD008953.pub2. </electronic-resource-num></record></Cite></EndNote>(6). This lack of evidence-based interventions leaves clinicians and patients without options for symptom reduction. Despite this, many clinicians continue to employ unsystematic, non-intensive, non-evidenced based treatments for degenerative ataxias ADDIN EN.CITE <EndNote><Cite><Author>Fonteyn</Author><Year>2013</Year><RecNum>11932</RecNum><DisplayText>(26)</DisplayText><record><rec-number>11932</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1457348269">11932</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fonteyn, Ella M. R.</author><author>Keus, Samyra H. J.</author><author>Verstappen, Carla C. P.</author><author>Sch?ls, Ludger</author><author>Groot, Imelda J. M.</author><author>Warrenburg, Bart P. C.</author></authors></contributors><titles><title>The effectiveness of allied health care in patients with ataxia: a systematic review</title><secondary-title>Journal of Neurology</secondary-title></titles><periodical><full-title>Journal of Neurology</full-title><abbr-1>J Neurol</abbr-1></periodical><pages>251-258</pages><volume>261</volume><number>2</number><dates><year>2013</year></dates><isbn>1432-1459</isbn><label>Fonteyn2013</label><work-type>journal article</work-type><urls><related-urls><url>;(26). The lack of ataxia-specific expertise in speech rehabilitation reinforces the need for education and evidence-based guidelines ADDIN EN.CITE <EndNote><Cite><Author>Corben</Author><Year>2014</Year><RecNum>11584</RecNum><DisplayText>(17)</DisplayText><record><rec-number>11584</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1424664199">11584</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Corben, L.A.</author><author>Lynch, D.</author><author>Pandolfo, M.</author><author>Schulz, J.B.</author><author>Delatycki, M.B.</author></authors></contributors><titles><title>Consensus clinical management guidelines for Friedreich ataxia</title><secondary-title>Orphanet Journal of Rare Diseases</secondary-title></titles><periodical><full-title>Orphanet journal of rare diseases</full-title></periodical><pages>184</pages><volume>9</volume><number>1</number><dates><year>2014</year></dates><isbn>1750-1172</isbn><urls></urls></record></Cite></EndNote>(17). Without these, ataxia patients are left without hope when faced with declining function and remain desperate for options to improve performance ADDIN EN.CITE <EndNote><Cite><Author>Gibilisco</Author><Year>2013</Year><RecNum>11119</RecNum><DisplayText>(3)</DisplayText><record><rec-number>11119</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1386112774">11119</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gibilisco, P.</author><author>Vogel, A.P.</author></authors></contributors><titles><title>Friedreich ataxia</title><secondary-title>BMJ</secondary-title></titles><periodical><full-title>BMJ</full-title></periodical><volume>347</volume><dates><year>2013</year><pub-dates><date>2013-12-03 11:17:14</date></pub-dates></dates><urls></urls><electronic-resource-num>10.1136/bmj.f7062</electronic-resource-num></record></Cite></EndNote>(3).Evidence based treatment for dysarthria is extremely limited but desperately needed Our successful pilot trial of a speech treatment in hereditary ataxias using principles of motor learning (PML) (ie. relating to structure of practice and feedback), neuroplasticity, and biofeedback as well as interventions by Synofzik/Sch?ls delivered via physiotherapy or highly motivating exergames have proven effective. What does speech in ataxia sound like?Instrumental and perceptual studies show speech in those affected by hereditary ataxia is characterised by reduced or uncontrolled variation in pitch and loudness, a slower rate of speech, poor voice quality ADDIN EN.CITE <EndNote><Cite><Author>Vogel</Author><Year>2016</Year><RecNum>12081</RecNum><DisplayText>(22)</DisplayText><record><rec-number>12081</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1470713746">12081</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vogel, A.P.</author><author>Wardrop, Mayumi I.</author><author>Folker, Joanne E.</author><author>Synofzik, Matthis</author><author>Corben, Louise A.</author><author>Delatycki, Martin B.</author><author>Awan, Shaheen N.</author></authors></contributors><titles><title>Voice in Friedreich Ataxia</title><secondary-title>Journal of Voice</secondary-title></titles><periodical><full-title>Journal of Voice</full-title></periodical><keywords><keyword>hereditary ataxia</keyword><keyword>clinical markers</keyword><keyword>dysarthria</keyword><keyword>acoustics</keyword><keyword>dysphonia</keyword></keywords><dates><year>2016</year></dates><isbn>0892-1997</isbn><urls><related-urls><url>;(22), imprecise production of consonants and vowels, nasal resonance issues ADDIN EN.CITE <EndNote><Cite><Author>Poole</Author><Year>2015</Year><RecNum>11515</RecNum><DisplayText>(23)</DisplayText><record><rec-number>11515</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1418790325">11515</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Poole, M.L.</author><author>Wee, J.S.</author><author>Folker, J.E.</author><author>Corben, L.A.</author><author>Delatycki, M.B.</author><author>Vogel, A.P.</author></authors></contributors><titles><title>Nasality in Friedreich ataxia</title><secondary-title>Clinical Linguistics & Phonetics</secondary-title></titles><periodical><full-title>Clinical Linguistics & Phonetics</full-title></periodical><pages>46-58</pages><volume>29</volume><number>1</number><dates><year>2015</year></dates><accession-num>25207996</accession-num><urls><related-urls><url>;(23) and reduced intelligibility PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmVuZGVsPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48
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ADDIN EN.CITE.DATA (4, 8). 2.2 RATIONALE FOR PROJECTWHAT IS NEEDED: An evidence-based speech rehabilitation program that caters to the physical, sensory and motor limitations of people with progressive hereditary ataxias.WE WILL ADDRESS THIS BY evaluating a program that:Employs an individually randomized controlled, assessor blinded parallel group study design;Is based on PML relating to feedback and intensity of treatment;Uses multi-sensory feedback (eg. aural, visual) to maximise opportunities for self-monitoring;Caters to the physical limitations of patients (ie. Digitized, home-based, large visual display);Mitigates the adverse effect of clinical services that cannot offer intensive face to face treatment;Is adaptable for use with other neurodegenerative diseases given its modular design;Is less expensive than standard intensive face to face treatments delivered by clinicians;Is ready for direct translation and application in clinical practice.Is employable by patients themselves in their home, thus pulling down access barriers and strengthening patient self-empowerment2.3 PRINCIPLES UNDERPINNING THE INTERVENTIONThe intensive four-week speech exercise programme (SpeechAtax) is designed to improve speech in people progressive hereditary ataxia. The treatment protocol is based on PML and neuroplasticity with a focus on improving speech intelligibility and vocal control. Exercises and feedback were created to enhance self-monitoring and include computer based aural, visual and results feedback and self-management.The proposed intervention will result in a significant advance in both our knowledge and ability to manage patients in degenerative ataxias. The planned research will translate rapidly into clinical practice. The neuropathology of ataxia dictates the need for multi-sensory feedback in rehabilitation The cerebellar cortex receives information from most parts of the body and from other regions of the brain ADDIN EN.CITE <EndNote><Cite><Author>Eccles</Author><Year>2013</Year><RecNum>11841</RecNum><DisplayText>(27)</DisplayText><record><rec-number>11841</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455007936">11841</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Eccles, J.C.</author><author>Ito, M.</author><author>Szentagothai, J.</author></authors></contributors><titles><title>The cerebellum as a neuronal machine</title></titles><section>335</section><dates><year>2013</year></dates><pub-location>New York, USA</pub-location><publisher>Springer Science & Business Media</publisher><isbn>3662131471</isbn><urls></urls></record></Cite></EndNote>(27). The cerebellum integrates this information and sends signals back to the rest of the brain to enable accurate and well-coordinated feed-forward/back movements. Where damage to the feed-forward signal is observed, as in virtually all hereditary ataxias, additional feedback is required to support correction of the stored representation to improve feed-forward motor control. Even healthy speakers need to learn, maintain and adjust prediction mechanisms (feedforward) by comparing predicted and observed speech output. Speech production is complex and involves adaptive and compensatory mechanisms that are proposed to be based on stored representations of intended speech output ADDIN EN.CITE <EndNote><Cite><Author>Houde</Author><Year>1998</Year><RecNum>8162</RecNum><DisplayText>(28)</DisplayText><record><rec-number>8162</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="0">8162</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Houde, J.F.</author><author>Jordan, M.I.</author></authors></contributors><titles><title>Sensorimotor Adaptation in Speech Production</title><secondary-title>Science</secondary-title></titles><periodical><full-title>Science</full-title></periodical><pages>1213-1216</pages><volume>279</volume><number>5354</number><dates><year>1998</year><pub-dates><date>February 20, 1998</date></pub-dates></dates><urls><related-urls><url>;(28). When there is a mismatch between speech output and the stored representation of intended speech, adjustments are meant to be made in real time ADDIN EN.CITE <EndNote><Cite><Author>Tremblay</Author><Year>2003</Year><RecNum>4217</RecNum><DisplayText>(29)</DisplayText><record><rec-number>4217</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="0">4217</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tremblay, S.</author><author>Shiller, D.M.</author><author>Ostry, D.J.</author></authors></contributors><titles><title>Somatosensory basis of speech production</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>866-869</pages><volume>423</volume><number>6942</number><dates><year>2003</year></dates><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>(29). By providing multiple opportunities for adjusting speech output (through feedback delivered aurally, visually or results ratings) we are able to maximise opportunities for refinement of motor output. Motor skill acquisition and retention is possible in ataxiaWe know the structure of an adult human brain changes in response to environmental demands ADDIN EN.CITE <EndNote><Cite><Author>Draganski</Author><Year>2004</Year><RecNum>11317</RecNum><DisplayText>(30)</DisplayText><record><rec-number>11317</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1399642814">11317</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Draganski, B.</author><author>Gaser, C.</author><author>Busch, V.</author><author>Schuierer, G.</author><author>Bogdahn, U.</author><author>May, A.</author></authors></contributors><titles><title>Neuroplasticity: Changes in grey matter induced by training</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>311-312</pages><volume>427</volume><number>6972</number><dates><year>2004</year><pub-dates><date>01/22/print</date></pub-dates></dates><publisher>Nature Publishing Group</publisher><isbn>0028-0836</isbn><work-type>10.1038/427311a</work-type><urls><related-urls><url>;(30). We also know that structural reorganisation in grey and white matter architecture occurs during motor skill learning ADDIN EN.CITE <EndNote><Cite><Author>Dayan</Author><Year>2011</Year><RecNum>11682</RecNum><DisplayText>(31)</DisplayText><record><rec-number>11682</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1434024111">11682</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dayan, E.</author><author>Cohen, L.G.</author></authors></contributors><titles><title>Neuroplasticity Subserving Motor Skill Learning</title><secondary-title>Neuron</secondary-title></titles><periodical><full-title>Neuron</full-title></periodical><pages>443-454</pages><volume>72</volume><number>3</number><dates><year>2011</year><pub-dates><date>11/3/</date></pub-dates></dates><isbn>0896-6273</isbn><urls><related-urls><url>;(31). Motor skills are typically learned slowly over multiple training sessions until performance reaches asymptotic levels ADDIN EN.CITE <EndNote><Cite><Author>Doyon</Author><Year>2005</Year><RecNum>11842</RecNum><DisplayText>(32)</DisplayText><record><rec-number>11842</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455080106">11842</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Doyon, J.</author><author>Benali, H.</author></authors></contributors><titles><title>Reorganization and plasticity in the adult brain during learning of motor skills</title><secondary-title>Current Opinion in Neurobiology</secondary-title></titles><periodical><full-title>Current opinion in neurobiology</full-title></periodical><pages>161-167</pages><volume>15</volume><number>2</number><dates><year>2005</year><pub-dates><date>4//</date></pub-dates></dates><isbn>0959-4388</isbn><urls><related-urls><url>;(32). Given that skill changes occur during and after training, there are many opportunities where new or reinforced speech skills will be consolidated through passive practice (e.g. talking to friends) ADDIN EN.CITE <EndNote><Cite><Author>Kleim</Author><Year>2008</Year><RecNum>11845</RecNum><DisplayText>(33)</DisplayText><record><rec-number>11845</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455081027">11845</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kleim, J.A.</author><author>Jones, T.A.</author></authors></contributors><titles><title>Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation After Brain Damage</title><secondary-title>Journal of Speech, Language, and Hearing Research</secondary-title></titles><periodical><full-title>Journal of Speech, Language, and Hearing Research</full-title></periodical><pages>S225-S239</pages><volume>51</volume><number>1</number><dates><year>2008</year></dates><isbn>1092-4388</isbn><urls><related-urls><url>(2008/018)</url></related-urls></urls><electronic-resource-num>10.1044/1092-4388(2008/018)</electronic-resource-num></record></Cite></EndNote>(33). New or reinforced skills and post therapy gains can be maintained over time, resulting in long-term retention ADDIN EN.CITE <EndNote><Cite><Author>Dayan</Author><Year>2011</Year><RecNum>11682</RecNum><DisplayText>(31, 34)</DisplayText><record><rec-number>11682</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1434024111">11682</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dayan, E.</author><author>Cohen, L.G.</author></authors></contributors><titles><title>Neuroplasticity Subserving Motor Skill Learning</title><secondary-title>Neuron</secondary-title></titles><periodical><full-title>Neuron</full-title></periodical><pages>443-454</pages><volume>72</volume><number>3</number><dates><year>2011</year><pub-dates><date>11/3/</date></pub-dates></dates><isbn>0896-6273</isbn><urls><related-urls><url> app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="0">8012</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schulz, G.M.</author><author>Dingwall, W.O.</author><author>Ludlow, C.L.</author></authors></contributors><titles><title>Speech and oral motor learning in individuals with cerebellar atrophy</title><secondary-title>Journal of Speech, Language & Hearing Research</secondary-title></titles><periodical><full-title>Journal of Speech, Language & Hearing Research</full-title></periodical><pages>1157-1175</pages><volume>42</volume><number>5</number><keywords><keyword>practice effects</keyword><keyword>voice</keyword><keyword>speech</keyword></keywords><dates><year>1999</year><pub-dates><date>October 1, 1999</date></pub-dates></dates><urls><related-urls><url>;(31, 34).PML are employed to enhance retention and transfer of speech skills practiced during intervention to everyday speech. They focus on structure of practice (ideally distributed, random, and variable practice, with high intensity over a sustained period) and structure of feedback (ideally knowledge of results (better/worse), delayed and low frequency feedback) and have been effective in limb motor learning and more recently utilised in speech treatments PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYXJrPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (7, 35). A recent trial by Theodoros showed substantial improvements in speech intelligibility following intensive dysarthria treatment in non-progressive dysarthria ADDIN EN.CITE <EndNote><Cite><Author>Park</Author><Year>2016</Year><RecNum>11848</RecNum><DisplayText>(35)</DisplayText><record><rec-number>11848</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455440223">11848</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Park, S.</author><author>Theodoros, D.G.</author><author>Finch, E.</author><author>Cardell, E.</author></authors></contributors><titles><title>Be Clear: A New Intensive Speech Treatment for Adults With Nonprogressive Dysarthria</title><secondary-title>American Journal of Speech-Language Pathology</secondary-title></titles><periodical><full-title>American Journal of Speech-Language Pathology</full-title></periodical><pages>97-110</pages><volume>25</volume><number>1</number><dates><year>2016</year></dates><isbn>1058-0360</isbn><urls><related-urls><url>;(35). These assumptions are corroborated by work of Synofzik and Sch?ls in physiotherapy and exergame studies in humans PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JbGc8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA (12-14, 16, 36) and animal studies, which demonstrate motor learning effects in mice with degenerative ataxia even on a molecular level ADDIN EN.CITE <EndNote><Cite><Author>Fryer</Author><Year>2011</Year><RecNum>11835</RecNum><DisplayText>(10)</DisplayText><record><rec-number>11835</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1454634105">11835</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fryer, J.D.</author><author>Yu, P.</author><author>Kang, H.</author><author>Mandel-Brehm, C.</author><author>Carter, A.N.</author><author>Crespo-Barreto, J.</author><author>Gao, Y.</author><author>Flora, A.</author><author>Shaw, C.</author><author>Orr, H.T.</author><author>Zoghbi, H.Y.</author></authors></contributors><titles><title>Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua</title><secondary-title>Science</secondary-title></titles><periodical><full-title>Science</full-title></periodical><pages>690-693</pages><volume>334</volume><number>6056</number><dates><year>2011</year><pub-dates><date>2011-11-04 00:00:00</date></pub-dates></dates><urls><related-urls><url>;(10).Home-based interventions are necessary and desirable in people with ataxiaOur rehabilitation work has been successfully implemented as home-based interventions. Many people with neurodegenerative disease – and in particular people with ataxia - present with significant mobility limitations leading to wheelchair dependence early in life ADDIN EN.CITE <EndNote><Cite><Author>La Pean</Author><Year>2008</Year><RecNum>11854</RecNum><DisplayText>(37)</DisplayText><record><rec-number>11854</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455585049">11854</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>La Pean, A.</author><author>Jeffries, N.</author><author>Grow, C.</author><author>Ravina, B.</author><author>di Prospero, N.A.</author></authors></contributors><auth-address>Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Bethesda, MD 20892-3705, United States
Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States
Memorial Neurosciences Department, Gulfport, MS, United States
Department of Neurology, University of Rochester Medical Center, Rochester, NY, United States</auth-address><titles><title>Predictors of progression in patients with Friedreich ataxia</title><secondary-title>Movement Disorders</secondary-title></titles><periodical><full-title>Movement Disorders</full-title></periodical><pages>2026-2032</pages><volume>23</volume><number>14</number><keywords><keyword>Friedreich ataxia</keyword><keyword>GAA expansion</keyword><keyword>Genotype</keyword><keyword>Medication</keyword><keyword>Phenotype</keyword></keywords><dates><year>2008</year></dates><work-type>Article</work-type><urls><related-urls><url>;(37). This practical concern can prevent patients from committing to intensive treatment or regular visits to health centres. The significant financial costs of: paying carers to accompany patients, transport associated with clinical visits (also physical barrier), and payment to clinicians for intensive therapy are additional barriers to centre based interventions ADDIN EN.CITE <EndNote><Cite><Author>Keating</Author><Year>2011</Year><RecNum>11847</RecNum><DisplayText>(38)</DisplayText><record><rec-number>11847</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455160396">11847</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Keating, A.</author><author>Lee, A.</author><author>Holland, A.E.</author></authors></contributors><titles><title>What prevents people with chronic obstructive pulmonary disease from attending pulmonary rehabilitation? A systematic review</title><secondary-title>Chronic Respiratory Disease</secondary-title></titles><periodical><full-title>Chronic Respiratory Disease</full-title></periodical><pages>89-99</pages><volume>8</volume><number>2</number><dates><year>2011</year><pub-dates><date>May 1, 2011</date></pub-dates></dates><urls><related-urls><url>;(38). A home-based program promotes access and works within clinical settings where intensive face to face contact is not possible or too expensive.3. STUDY DESIGN3.1 OVERALL DESIGNPRIMARY AIM: To improve speech intelligibility (ability to be understood) after 4 weeks in people with dysarthria resulting from degenerative ataxia using a biofeedback driven intensive home-based speech rehabilitation program compared with existing care.PRIMARY HYPOTHESIS: An intensive home-based treatment using multisensory feedback will improve speech intelligibility in patients with degenerative ataxia after 4 weeks.STUDY DESIGN: This study employs an individually randomized controlled, assessor blinded parallel group design of existing care vs SpeechATAX treatmentRANDOMISATION ALLOCATION AND CONCEALMENT: The randomisation list will be created by a third party (Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne). After informed consent and baseline assessments, participants will be randomly allocated 1:1 to either the intervention (home-based) or control (existing care) arm. The differing neuropathology between each ataxia group necessitates balancing ataxia type diagnosis across sites. A stratified block permuted randomisation list will be computer-generated using ataxia type (Friedreich’s ataxia, spinocerebellar ataxia) as stratification factor to achieve balance between the treatment arms within each clinic. The 5 sites can access the randomisation model through REDCap. -32248919630500Figure 2: SpeechATAX Study design4. STUDY POPULATION4.1 INCLUSIONARY CRITERIAProvision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18 years or olderConfirmed genetic diagnosis of Friedreich’s ataxia or Spinocerebellar ataxia type 1, 2, 3 or 64.2 EXCLUSIONARY CRITERIANo confirmed genetic diagnosis of Friedreich’s ataxia or spinocerebellar type 1, 2, 3 or 6. E.g. idiopathic progressive ataxia, non-progressive ataxiasSTUDY PROTOCOLRECRUITMENT5.1.1 RECRUITMENT SITESPotential participants will be identified and recruited from ataxia clinics in 5 distinct sites:Melbourne: Friedreich’s Ataxia Clinic, Monash Medical Centre, Melbourne and Ataxia Clinic, The Alfred Hospital, Melbourne (40 participants)Brisbane: Ataxia Clinic, The Royal Brisbane and Women’s Hospital (10 Participants)Tubingen: Tubingen University Hospital (20 participants)Auckland: Ataxia Clinic, Auckland City Hospital (15 participants)Paris: Friedreich’s Ataxia Clinic, Institute of the Brain and Spinal Cord, Paris. (15 participants)All data for the SpeechATAX trial will be collected and stored through REDCap, a web-based data collection tool. 5.1.2 INITIAL CONTACTParticipants may be recruited during their appointments at the ataxia clinics (section 5.1) or from patient lists from these clinics. A recruitment email and Plain Language Statement will be sent to any potentially interested participants. Participants may get in contact with the investigator directly following the Plain Language Statement, or a follow up call can be made after the initial email. Ensure the participant understands the commitment of the trial (4-5 assessments, 4 weeks of intensive therapy) and arrange a time for an initial assessment. 5.1.3 PARTICIPANT ASSIGNMENTPlease see Standard Operating Procedure for more information about data entry and randomisation through REDCapREDCap will automatically generate a participant code based on site for the participants. Melbourne: 752-XBrisbane: 753-XTubingen: 754-XAuckland: 755-XParis: 756-XEach site will only have access to the data within their site. 5.2. STUDY METHODOLOGY5.2.1 BASELINE/INITIAL ASSESSMENT – 90 minutesThe initial assessment will be completed in participant’s home at Melbourne, Brisbane and Auckland sites, and in the clinic in Tubingen in Paris sites. During this visit, participants will be given an explanation of the SpeechATAX trial and be given the opportunity to ask questions. Obtain written consent from participant (consent form)Create participant on RedenLab using the REDCap generated code, DOB and sex. See SOP for recording speech on RedenLab. The following assessments are completed;A speech sample is recorded using RedenLab (USING BASELINE/VISIT 1) and a high-quality microphone (AKG), external soundcard (QUAD-CAPTURE) and a laptop. All stimuli are elicited at a comfortable pitch and vocal effort. All stimuli are elicited at a comfortable pitch and vocal effort. Stimuli include (a) reading a brief passage (North Wind and the Sun); (b) automatic speech task: days of the week (c) prolonged production of vowels: sustain an open “ah” vowel for as long as possible; (d) syllable repetition: saying PATAKA as quickly and as clearly as possible; (e) monologue: for one minute on a topic of choice. (10 minutes)Cerebellar Cognitive Affective Scale (the first 3 verbal fluency tasks will be recorded on RedenLab) (15 minutes)Scale for the Assessment and Rating of Ataxia (15 minutes)Hearing Assessment (15 minutes)Speech perception in noise – CNC words (15 minutes)Dysarthria Impact Score (10 minutes)Communicative Effectiveness Scale (CES) – communication partner perspective (5 minutes). Informal survey about current speech therapyParticipants will then randomized to Group A (direct treatment) or Group B (delayed entry). Participants will be informed of timelines for SpeechATAX therapy (Group A-one month, Group B-2 months)Arrange an appointment in 4 weeks for next assessment5.2.2 MONITORING ASSESSMENT (GROUP B ONLY) – 30 minutesThe monitoring assessment will be completed in participant’s home at Melbourne, Brisbane and Auckland sites, and in the clinic in Tubingen in Paris sites.The following assessments are completed; A speech sample is recorded using RedenLab (USING VISIT 2) and a high quality microphone (AKG), external soundcard (QUAD-CAPTURE) and a laptop. All stimuli are elicited at a comfortable pitch and vocal effort. All stimuli are elicited at a comfortable pitch and vocal effort. Stimuli include (a) reading a brief passage (North Wind and the Sun); (b) automatic speech task: days of the week (c) prolonged production of vowels: sustain an open “ah” vowel for as long as possible; (d) syllable repetition: saying PATAKA as quickly and as clearly as possible; (e) monologue: for one minute on a topic of choice. (10 minutes).Dysarthria Impact Score (10 minutes)Arrange an appointment in 4 weeks for the next assessment5.2.3 PRE-TREATMENT ASSESSMENT/SPEECHATAX SETUP – 90 minutesThe pre-treatment assessment will be completed in participant’s home at Melbourne, Brisbane and Auckland sites, and in the clinic in Tubingen in Paris sites.This assessment is 4 weeks post-baseline for Group A and 8 weeks post-baseline for Group B.The following assessments are completed; Speech samples recorded using RedenLab (USING VISIT 2 for Group A and VISIT 3 for GROUP B) and a high-quality microphone (AKG), external soundcard (QUAD-CAPTURE) and a laptop. All stimuli are elicited at a comfortable pitch and vocal effort. All stimuli are elicited at a comfortable pitch and vocal effort. Stimuli include (a) reading a brief passage (North Wind and the Sun); (b) automatic speech task: days of the week (c) prolonged production of vowels: sustain an open “ah” vowel for as long as possible; (d) syllable repetition: saying PATAKA as quickly and as clearly as possible; (e) monologue: for one minute on a topic of choice. (10 minutes).Dysarthria Impact Score (10 minutes)Global Efficacy Questionnaire – informal questionnaire about perceptions of home-based therapy. Explanation of SpeechATAX therapy requirements: 5 times per week for 4 weeks (20 days in total), approximately 45 minutes per day, weekly phone calls with study administrators to monitor progressExplanation of key SpeechATAX features: exercises designed specifically for people with progressive ataxia, biofeedback mechanisms designed to improve self-awareness of speech, speech recordings uploaded to study administrator to monitor progressParticipants complete the first day of SpeechATAX therapy with the study administrator (see section 6.4)Use the Date Arrangement timetable to schedule an appointment in 4 weeks for the next assessment and 4-5 phone/skype calls to monitor participant progress with the therapy. 5.2.4 WEEKLY PROGRESS/MOTIVATION PHONECALLS One phone or skype call 2 days after therapy, then one phone or skype call per week for the 4 weeks of therapy. The clinician should regularly listen to the participant recordings on RedenLab – listen to a few for each task for the week, identify areas of strengths and areas for improvement. Contact should be used to answer questions, oversee the correct performance of the exercises and model them if necessary, as well as reviewing the compliance of the protocol. The participant should aim to complete 5 days of SpeechATAX between each phone call. The clinician should keep the participant on track for this timeline. 5.2.5 POST-TREATMENT ASSESSMENT/MAINTENANCE PHASE OF SPEECHATAX – 60 minutesThe post-treatment assessment will be completed in participant’s home at Melbourne, Brisbane and Auckland sites, and in the clinic in Tubingen in Paris sites.This post-treatment assessment is 8 weeks post-baseline for Group A and 12 weeks post-baseline for Group B.The following assessments are completed with the participant during the post-treatment assessment: A speech sample is recorded using RedenLab (USING VISIT 3 for Group A and VISIT 4 for GROUP B) and a high-quality microphone (AKG), external soundcard (QUAD-CAPTURE) and a laptop. All stimuli are elicited at a comfortable pitch and vocal effort. All stimuli are elicited at a comfortable pitch and vocal effort. Stimuli include (a) reading a brief passage (North Wind and the Sun); (b) automatic speech task: days of the week (c) prolonged production of vowels: sustain an open “ah” vowel for as long as possible; (d) syllable repetition: saying PATAKA as quickly and as clearly as possible; (e) monologue: for one minute on a topic of choice. (10 minutes).Dysarthria Impact Score (10 minutes)Global Efficacy Questionnaire – informal questionnaire about perceptions of home-based therapy. Communicative Effectiveness Scale – communication partner perspectiveExplanation of SpeechATAX maintenance phase requirements: “free practice” participant is able to use the therapy as much or as little as they like (recommended 3 x per week), approximately 30 minutes per day, no weekly phone calls. Complete Day 21 of SpeechATAX with participant (first day of maintenance phase) Arrange an appointment in 4 weeks for the next assessment5.2.6 MAINTENANCE ASSESSMENT – 45 minutesThe maintenance assessment will be completed in participant’s home at Melbourne, Brisbane and Auckland sites, and in the clinic in Tubingen in Paris sites.This maintenance assessment is 12 weeks post-baseline for Group A and 16 weeks post-baseline for Group B.The following assessments are completed with the participant during the post-treatment assessment: Speech samples recorded using RedenLab (USING VISIT 4 for Group A and VISIT 5 for GROUP B) and a high-quality microphone (AKG), external soundcard (QUAD-CAPTURE) and a laptop. All stimuli are elicited at a comfortable pitch and vocal effort. All stimuli are elicited at a comfortable pitch and vocal effort. Stimuli include (a) reading a brief passage (North Wind and the Sun); (b) automatic speech task: days of the week (c) prolonged production of vowels: sustain an open “ah” vowel for as long as possible; (d) syllable repetition: saying PATAKA as quickly and as clearly as possible; (e) monologue: for one minute on a topic of choice. (10 minutes).Dysarthria Impact Score (10 minutes)SpeechATAX Feedback (15 minutes) – informal questionnaire of participant perceptions of their experience with SpeechATAX. Thank you and closing. Participant can be provided with SpeechATAX paper-based materials if they would like.5.3. ASSESSMENT SCHEDULES5.3.1 GROUP A TIMETABLE FOR DATA COLLECTIONASSESSMENTBaselinePre-treatmentPost-treatmentMaintenance Participant DetailsRandomisationSpeech SampleCCASScale for the Assessment and Rating of Ataxia (SARA)SARA Speech ItemAudiogramCNC WordsDysarthria Impact ScoreCES – communication partner perspectiveGlobal Efficacy QuestionnaireSpeechATAX Feedback5.3.2 GROUP B TIMETABLE FOR DATA COLLECTIONDATA COLLECTIONBaselineMonitoringPre-treatmentPost-treatmentMaintenanceParticipant DetailsRandomisationSpeech SampleCCASScale for the Assessment and Rating of Ataxia (SARA)SARA Speech ItemAudiogramCNC WordsDysarthria Impact ScoreCES– communication partner perspectiveGlobal Efficacy QuestionnaireSpeechATAX Feedback6. DETAILS OF INTERVENTION6.1 BACKGROUNDOur characterisation work of speech deficits resulting from ataxia has identified three broad areas of deficit that are the goals of treatment PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb2xrZXI8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (38, 47). Interventions targeting dysprosody have been successfully applied to related populations such as PD and stroke. Prosody interventions can focus on producing meaningful prosodic contrasts at the word and phrase level ADDIN EN.CITE <EndNote><Cite><Author>Hargrove</Author><Year>2013</Year><RecNum>11929</RecNum><DisplayText>(48)</DisplayText><record><rec-number>11929</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1457321099">11929</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hargrove, P.M.</author></authors></contributors><titles><title>Pursuing prosody interventions</title><secondary-title>Clinical Linguistics & Phonetics</secondary-title></titles><periodical><full-title>Clinical Linguistics & Phonetics</full-title></periodical><pages>647-660</pages><volume>27</volume><number>8</number><dates><year>2013</year><pub-dates><date>2013/08/01</date></pub-dates></dates><publisher>Taylor & Francis</publisher><isbn>0269-9206</isbn><urls><related-urls><url>;(48). Vocal control exercises have demonstrated therapeutic benefit in dysarthria (eg. PD, stroke) requiring participants to focus on accurate coordination of respiratory and phonatory systems ADDIN EN.CITE <EndNote><Cite><Author>Tamplin</Author><Year>2008</Year><RecNum>11931</RecNum><DisplayText>(49)</DisplayText><record><rec-number>11931</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1457324863">11931</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tamplin, J.</author></authors></contributors><titles><title>A pilot study into the effect of vocal exercises and singing on dysarthric speech</title><secondary-title>NeuroRehabilitation</secondary-title></titles><periodical><full-title>NeuroRehabilitation</full-title></periodical><pages>207-216</pages><volume>23</volume><number>3</number><dates><year>2008</year></dates><isbn>1053-8135</isbn><urls></urls></record></Cite></EndNote>(49).Table 2: Components of therapy designStimuli [indicates associated Tx goal]Daily tasks: i) words and sentences [Intel]; ii) Long vowel x 10 repetitions [Control]; iii) loudness and pitch control exercises x 10 each [Control]; iv) short phrases with target word designed to improve prosody x 15 [Prosody]; v) reading task [All 3 goals]; vi) transfer exercise (daily question) [All 3 goals]Elicitation methodImitation of clinician’s production in first session and on weekly calls, then reading stimuli on PCs for non-supervised sessionsTeaching strategies/cuesInitial session and weekly follow-up: Verbal instructions, modelling and training on interpretation of feedbackFeedbackAural and visual via biofeedback and knowledge of results via acoustic outcomes of duration, pitch and loudness variationWe have created treatment software called SpeechAtax with a simple user interface suitable for use on hardware available to the patient or clinician. We will use the same Samsung Galaxy Tablets (16GB, 10.1 inch) across all sites (plus Logitech headset microphone) for all participants to standardise treatment delivery. Participants are trained on the principles and practicalities of SpeechAtax in the first session. They are provided with the software pre-installed on the Samsung Galaxy. Participants are contacted weekly via Skype/phone until the end of therapy at 4 weeks. Contact is important for monitoring progress and compliance with treatment principles. Recordings and acoustic measures made during therapy will be captured and reviewed post treatment to audit adherence and trajectory. 6.2 BIOFEEDBACK Tasks are designed to enhance one of three areas of production: improved intelligibility, vocal control and natural prosodic variation. The program utilises both aural, visual and results feedback (self-comparison) (see below). The multiple biofeedback modalities are designed to focus the speaker on external controls of speech, thus enhancing their own monitoring of production.A: Visual feedback:Visual feedback is provided through the real time loudness display. Patients can monitor the stability or variability of their loudness while speaking. For example, if patients cannot see any colour in the visual display they need to increase the loudness of their speech. Similarly, a stable production is required for the long vowel task, meaning the visual display should remain at a constant level throughout the production.The feedback given by the interface supports the patient by training self-awareness. Loudness is represented visually, providing an alternative mode of feedback other than listening. Demonstrate and encourage the use of these feedback options.-42989522288500B: Aural (listening) feedback: Patients are prompted to record parts of their speech each day. They are then required to listen to their recorded sample from the previous day. Listening feedback is designed to enhance self-monitoring and help the speaker identify aspects of their speech that need improvement.Listening to speech can be upsetting for some patients but it is a vital component of therapy. Delayed aural feedback is important for the development of self-monitoring skills by providing an opportunity to hear their performance, identify what worked and what went wrong and set some goals for the day.-22860017780000C: Outcome feedback:Patients are provided with immediate and objective feedback of their performance. Three pieces of information are derived from the recorded samples and compared against the previous days’ scores:1.Duration, which is important for the long vowel task; 2-3 Loudness and pitch variation, both of which are important for the vowel and connected speech tasks. This information is designed to enhance the patient’s understanding of their performance and to provide a benchmark on which to compare earlier productions.-320040281940006.3 EXERCISESDaily tasks undertaken by participant at home [CAPITALS INDICATE GOAL]Sustained phonation: hold the vowel /ah/ in a stable and clear voice (10 repetitions). Participants complete task while receiving visual feedback on vocal stability on their screen noting. They are also provided with performance feedback (comparison with previous days’ production) on the duration, quality and loudness of their speech. VOCAL CONTROL & BREATH SUPPORTCrescendo-decrescendo - loudness: hold the vowel /ah/ at a constant pitch, beginning softly then becoming gradually louder then gradually softer again (10 repetitions). VOCAL CONTROL Pitch glide: hold the vowel /ah/ at a constant loudness, start on a low pitch, glide up to the highest pitch and then glide back down again (10 repetitions) VOCAL CONTROLEmphasis/stress: Read the 15 five-word sentences aloud (stimuli vary each day). The speaker is required to place stress on the highlighted word within the phrase. PROSODYWords and phrases: Participants are asked to ‘over-enunciate’ when producing stimuli of varying complexities (ie. monosyllabic, multisyllabic words, phrases, conversation) ADDIN EN.CITE <EndNote><Cite><Author>Lam</Author><Year>2013</Year><RecNum>11029</RecNum><DisplayText>(50)</DisplayText><record><rec-number>11029</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1382493931">11029</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lam, J.</author><author>Tjaden, K.</author></authors></contributors><titles><title>Intelligibility of Clear Speech: Effect of Instruction</title><secondary-title>Journal of Speech, Language & Hearing Research</secondary-title><alt-title>J Speech Lang Hear Res</alt-title></titles><periodical><full-title>Journal of Speech, Language & Hearing Research</full-title></periodical><alt-periodical><full-title>J Speech Lang Hear Res</full-title></alt-periodical><pages>1429-1440</pages><volume>56</volume><number>5</number><dates><year>2013</year><pub-dates><date>October 1, 2013</date></pub-dates></dates><urls><related-urls><url>(2013/12-0335)</electronic-resource-num></record></Cite></EndNote>(50). Tasks help participants apply skills they are reinforcing during the repetitive set daily tasks. They also provide a foundation on which to generalise performance post treatment. INTELLIGIBILITYReading a passage of interest to the participant. Task is recorded and listened to the following day [aural feedback]. Participants are asked to listen and attend to aspects of speech needing improvement. INTELLIGIBILITYDaily question: A new question is asked each day. The speaker is required to apply and reinforce all skills learnt during the session to produce the most intelligible and natural speech possible. INTELLIGIBILITY and PROSODYConversation (day 16-20): The speaker is required to apply and reinforce all skills learnt during the session to produce the most intelligible and natural speech possible for 1-2 minutes of spontaneous speech. INTELLIGIBILITY and PROSODY6.4. SPEECHATAX SET UP6.4.1 Explanation of therapy goals and contentsIntroduce goals of therapy: Improvement of articulation, pronunciation, vocal quality and control, and overall intelligibilityTalk about the therapy activities and how they change over the program Stress the responsibility for completing tasks lies with the patient. Clearly articulate what is expected each day.6.4.2 Instructions for the use of the therapy software and specific trainingThe software should be installed on the Samsung Galaxy and a username and password should be created for the patient:Download the therapy from speechtherapy. Allow installations from unknown sources. Settings Lock Screen and Security Unknown sources “on”Login to SpeechATAX and connect to the participant’s home internet. This will ensure that the speech files can be uploaded to the server for clinician monitoring. Explain how a Samsung Galaxy is used if required – where the on/off button is, how to close apps, volume etc. Familiarise the patient with the therapy program.Elaborate on the following functions: Starting and closing the program, how to use the visual feedback options, recording and replaying of exercises, what the acoustic variables mean and how to interpret plete day 1 during this session with patient. Ensure you model appropriate production and identify aspects of patient’s speech/voice that need improvement.While discussing the particular exercises with the patient, it is important to be consistent in your terminology. Also make sure that all terms and instructions used in the protocol have been understood and described correctly (e.g. over-enunciated talking, sustaining /ah/ as long as voice quality is good, etc.).Demonstrate how to produce each task before asking the patient to perform the exercises.Ensure your patient adopts good posture and breathing during the exercises: sitting upright and appropriate head position. Highlight good voice quality and pay attention to undesired compensatory-strategies (e.g., postural changes, clavicular breathing).Encourage the patient's self-awareness by jointly evaluating his/her body position and execution of the exercises. Note individual difficulties so you can bring them up during the weekly phone calls.If possible have your own Samsung Galaxy open on day 2-20 as there are no replay/graph functions on day 1. This helps to explain the visual and auditory feedback to the patient. Explain troubleshooting procedures for SpeechATAX:Turn Samsung Galaxy off and onClose app and restartEnsure Samsung Galaxy is fully chargedNotify clinician if experiencing persistent difficulties. 7. STUDY DISCONTINUATION/PARTICIPANT WITHDRAWALParticipation in the study is voluntary and participants are free to withdraw from the study at any time upon request.Study administrators may discontinue or withdraw a participant from the study for the following reasons:If any adverse event or medical situation occurs such that continued participation would not be in the best interest of the participant. Significant study intervention non-compliance: SpeechATAX is required to be completed 5 x week for 4 weeks (20 days in total). If unforeseen circumstances prevent the participant from completing the therapy (e.g. illness, family circumstances etc.) within 4 weeks, participants may have 2 additional weeks to complete SpeechATAX. The post-treatment assessment must be within 6 weeks of the pre-treatment assessment in order for the data to be included. These discontinuations/withdrawals/extensions must be documented in REDCap. 8. OUTCOME MEASURES8.1 OUTCOME MEAUSRESAssessments will be conducted according to the timeline in SECTION 5. All data to be entered in REDCap. 8.1.1 DESCRIPTIVE MEASURESCognitive examination (Cerebellar Cognitive Affective/Schahmann Syndrome Scale (CCAS). All participants will receive a standardised cognitive examination specifically for cerebellar conditions. (10 minutes)Neurological examination (Scale for the Assessment and Rating of Ataxia (SARA)) (55). All participants will receive a standardised neurological examination for overall ataxia severity. (15 minutes)Audiogram: Sound detection thresholds will be measured at octave frequencies in the speech frequency range (250 Hz – 8 kHz). (15 minutes)Functional hearing ability (speech perception in noise: CNC Words): Most individuals with FRDA have difficulty understanding conversational speech in everyday listening conditions. Sentence perception in background noise will be evaluated using the CNC word test (+20dB, +0dB conditions, at comfortable listening level). (10 minutes)8.1.2 PRIMARY OUTCOME MEAUSRE Intelligibility: To be rated via expert perceptual judgement (blinded assessors) of the first 30 seconds from the monologue using direct magnitude estimation (DME). DME is a means of standardising subjective listener judgments. The technique is used with a reference stimulus chosen by consensus of experts as a good exemplar of "mild" dysarthria (given a score of 100). Raters then assign values greater than 100 to denote better performance on measures of intelligibility. For these parameters, a value of 200 indicates that a sample is rated twice as good as the reference sample, while a value of 50 denotes the sample is only half as intelligible compared with the reference. DME is considered more accurate and reliable than standard severity ratings ADDIN EN.CITE <EndNote><Cite><Author>Schiavetti</Author><Year>1981</Year><RecNum>11855</RecNum><DisplayText>(50)</DisplayText><record><rec-number>11855</rec-number><foreign-keys><key app="EN" db-id="t22zrprrqwxw2qeatrp59v09ea2zsztfeaf2" timestamp="1455585949">11855</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schiavetti, N.</author><author>Metz, D.E.</author><author>Sitler, R.W.</author></authors></contributors><titles><title>Construct Validity of Direct Magnitude Estimation and Interval Scaling of Speech IntelligibilityEvidence from a Study of the Hearing Impaired</title><secondary-title>Journal of Speech, Language, and Hearing Research</secondary-title></titles><periodical><full-title>Journal of Speech, Language, and Hearing Research</full-title></periodical><pages>441-445</pages><volume>24</volume><number>3</number><dates><year>1981</year></dates><isbn>1092-4388</isbn><urls><related-urls><url>;(50) for determining change.Query! Timepoint 3052950Baseline assessment (week 1), post baseline assessment at week 4 (and 8 weeks for group B). Then assessment immediately post treatment [primary timepoint], and again 4 weeks post completion of treatment for both groups. 8.1.3 SECONDARY OUTCOME MEASURESQuery! Secondary outcome [1] 3447640Paired comparison ratings of conversation by na?ve listeners. Listeners are asked to decide which of two audio-recorded samples (pre- and post-treatment, played in random order) is clearer. Informal objective rating scale will be used. Query! Timepoint [1] 3447640Baseline assessment (week 1), post baseline assessment at week 4 (and 8 weeks for group B). Then assessment immediately post treatment, and again 4 weeks post completion of treatment for both groups. Query! Secondary outcome [2] 3447650Objective measures of speech, including acoustic measures of timing (eg. pause length in reading and monologue tasks), vocal control (eg. fundamental frequency and loudness variation from vowel and monologue), and vocal quality (eg. dysphonia measures derived from sustained vowel). This is a composite secondary outcome. Query! Timepoint [2] 3447650Baseline assessment (week 1), post baseline assessment at week 4 (and 8 weeks for group B). Then assessment immediately post treatment, and again 4 weeks post completion of treatment for both groups. Query! Query! Secondary outcome [3] 3447680Speech-related quality of life (Dysarthria Impact Score, DIS). The DIS is a validated survey on the psychosocial impact of acquired dysarthria from the speaker’s perspective. Query! Timepoint [3] 3447680Baseline assessment (week 1), post baseline assessment at week 4 (and 8 weeks for group B). Then assessment immediately post treatment, and again 4 weeks post completion of treatment for both groups. Query! Secondary outcome [4] 3447710Communication partner perception (Communicative Effectiveness Survey, CES) The CES is a standardised survey describing domains of communication beyond intelligibility. Disorder-specific patient-reported outcomes will address issues unique to the condition being studied. Query! Timepoint [4] 3447710Baseline assessment (week 1) and assessment immediately post treatment, for both groups.Query! Query! Secondary outcome [5] 3447760Global Efficacy Questionnaire. An informal survey of participant/carer time/money will provide data on healthcare-related costs. This survey has been designed specifically for this study. Query! Timepoint [5] 3447760Pre-treatment and post-treatment assessment for both groups.9. STATISTICAL ANALYSISA detailed statistical analysis plan will be finalized before locking the database. The analysis will be undertaken on an intention-to-treat basis. The primary outcome speech intelligibility will be base-2 log-transformed before fitting a mixed-model to the measurements at immediately post-treatment and 4-weeks post treatment, including in the model baseline (log2), arm, week, and arm by week interaction as well as the stratification factor ataxia type. The primary hypothesis will be evaluated using the estimate and two-sided 95% CI of the geometric mean ratio of the home-based intervention to existing-care at 4 weeks. The treatment effect at 4-weeks post treatment will be examined similarly. The model provides valid inference if the underlying missing data mechanism is missing at random. The robustness of the results to this missing data assumption will be investigated using a pattern-mixture model (64). The clinical meaningfulness of the treatment effect on a patient level (ie. treatment responder) will be explored using a generalized mixed-model with a logit link fitted to responder status (yes/no) at immediately post-treatment and 4-weeks post-treatment. The estimate and two-sided 95% CI of the odds ratio of being a treatment responder following home-based intervention compared to existing care will be obtained immediately post-treatment and 4 weeks post-treatment. Continuous secondary outcomes will be analyzed using a similar model specification as the primary outcome, with (e.g., outcome on ratio scale or skewed) or without appropriate transformations before fitting the model. Binary secondary outcomes will be analyzed similarly to the analysis of treatment responders. Statistical oversight will be provided by our biostatistician, Sabine Braat (with near 20 years of experience in clinical trials).10.SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS10.1 CONSENT A consent form and Plain Language Statement describing in detail the study intervention, study procedures, and risks are given to the participant and written documentation of informed consent is required prior to starting intervention/administering study intervention. Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study and continues throughout the individual’s study participation. The investigator will explain the research study to the participant and answer any questions that may arise. A verbal explanation will be provided in terms suited to the participant’s comprehension of the purposes, procedures, and potential risks of the study and of their rights as research participants. Participants will have the opportunity to carefully review the written consent form/Plain Language Statement and ask questions prior to signing. The participants should have the opportunity to discuss the study with their family or think about it prior to agreeing to participate. The participant will sign the informed consent document prior to any procedures being done specifically for the study. Participants must be informed that participation is voluntary and that they may withdraw from the study at any time, without prejudice. The informed consent process will be conducted and documented in the source document (including the date), and the form signed, before the participant undergoes any study-specific procedures. The rights and welfare of the participants will be protected by emphasizing to them that the quality of their medical care will not be adversely affected if they decline to participate in this study.10.2 CONFIDENTIALITY AND PRIVACYParticipant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, and the sponsor(s) and their interventions. The study protocol, documentation, data, and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorized third party without prior written approval of the sponsor. All research activities will be conducted in as private a setting as possible. 10.3 DATA MANAGEMENTFor the duration of the trial data will be collected on REDCap. The study coordinator will have access to all data and will assign access rights to data collectors/investigators from other trial sites. Investigators will only have access to data from their own site (e.g. investigators in Brisbane will only have access to Brisbane participant data, not from any of the other sites). De-identified data will be entered into a password-protected computer database, which will be compressed and stored on a removable storage device at the University of Melbourne after the study. Data will be retained for 7 years. Information will be disposed of by secure destruction as per University policy. References ADDIN EN.REFLIST 1.Brady MC, Clark AM, Dickson S, Paton G, Barbour RS. The impact of stroke-related dysarthria on social participation & implications for rehabilitation. Disability & Rehabilitation. 2011;33(3):178-86.2.Northcott S, Moss B, Harrison K, Hilari K. A systematic review of the impact of stroke on social support & social networks: Associated factors & patterns of change. Clinical Rehabilitation. 2015.3.Gibilisco P, Vogel AP. Friedreich ataxia. BMJ. 2013;347.4.Bird TD. 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