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Assn of Academic Physiatrists

DJ Kennedy

January 22, 2014

10:05 a.m. CT

DJ Kennedy: Hello. Welcome to the Association of Academic of Academic Physiatrists Podcast featuring the American Journal of (PMR) Article from July 2013. Hypertonic dextrose and morrhuate sodium injections prolotherapy for lateral epicondylosis, tennis elbow, results of a single-blind, pilot-level, randomized control trial.

Today's podcast will include a Q and A with lead author, Dr. David Rabago on research conducted at the University of Wisconsin School of Medicine and Public Health in Madison.

I am DJ Kennedy a clinical assistant professor in the Physical Medicine and Rehabilitation at Stanford University. I'll be hosting this 15-minute podcast.

Welcome to the program, Dr. Rabago. Let's get started.

Your article has chosen to interest among members and readers. And can you briefly summarize the study for those who haven't had the opportunity to read it?

David Rabago: Sure. And Dr. Kennedy thanks for having me on the podcast today.

Our study was a pilot-level study meaning that er are interested in some of the basic questions associated with tennis elbow and its treatment with prolotherapy. We identified prolotherapy as a possible treatment for tennis elbow refractory to more conservative care. And it is a study that includes three arms in a randomized fashion.

The first arm received dextrose prolotherapy, the second dextrose in a solution with low concentration morrhuate sodium and the third was wait-and-see control group. As you know, it's unclear the effect of natural history, that is tincture of time on the outcomes associated with prolotherapy. And we really wanted to get an idea of the effects of treatment compared to a wait-and-see approach using the two most commonly used prolotherapy solutions.

DJ Kennedy: Wonderful. And what were the basic results from this study?

David Rabago: Well, we found that over the initial 16-week randomized portion of the study that each group did improve as expected. As you know for most people tennis elbow time alone does confer some advantageous effect. But we saw that the improvement in the wait-and-see control group was small and did not meet the so-called minimal important – minimal clinical important difference on our primary outcome measure which is a multi-dimensional questionnaire. And that the intervention groups did meet that criteria. I can go into specific point totals if you like. But basically the two intervention groups did better than did the wait-and-see control group.

DJ Kennedy: Yes. One of the interesting things that you actually did compare two different prolotherapy solutions, can you comment on your thought process for which one you utilize now based on the results of this study? And I commend you because you've actually done numerous other studies on this same topic in different disease populations. But can you give us a background as to your thought process? And to your credit you also have a discussion in the article on this as well.

David Rabago: Yes. Thanks for those kind words. We are quite excited about this therapy. The thought process went like this. I've collaborated with a sports physician, Dr. Michael Scarpone on a prior study and he used a prolotherapy solution involving morrhuate sodium and dextrose. And it was kind of his own cocktail based on his clinical experience.

And what we wanted to determine was whether or not more conventionally used solutions including dextrose alone which is by far the most commonly used solution would be able to equal his results. So we crafted a study design that would essentially try to replicate his morrhuate and dextrose solution and compare it to conventional dextrose alone. Dextrose has an advantage of being more readily available, less expensive and probably a little less irritating on injection to patients.

And so, that was the rationale for those two groups and as I mentioned the wait-and-see control was really kind of the benchmark standard by which we would determine whether or not there was benefit.

DJ Kennedy: So what is your thought process now that you the results of these – of this study, on which of the two dextrose solutions you would use if you were going to use this treatment?

David Rabago: I think that the data strongly support at least the initial use of hypertonic dextrose and the concentrations noted in the paper. This is safe, well-tolerated injection set for patients we didn't find the need for pre-injection analgesia. We did use skin wheels prior to injection. But in general patients tolerate it very well and the results at least in this pilot study between the two intervention groups was really similar.

DJ Kennedy: One of the things that I think excites probably a lot of the readers are the fact that this was an ultrasound-guided injection for accuracy purposes combined with a in theory fairly cheap solution that may not have the same systemic side effects. There are a lot of treatment algorithms proposed for lateral epicondylosis, probably the one with best research on it is but PRP has been proposed, corticosteroid injections for a long time were the standard care but maybe falling out of favor, non-steroidal .

Where do you see a treatment like this fitting in along the treatment continuum?

David Rabago: We see prolotherapy fitting into patient care in the following way. Part of it is due to what the patient is presenting with and part on what's been tried before. Initial presentation usually will involve treatment with counseling and making clear the notion that this therapy can take some time and the use of relative rest, especially in the context of overuse injury either at work or in activities, for example sports.

And physical therapy especially with the eccentric exercise is a next step and this is usually covered by patients’ insurance if they have insurance. And we give that a reasonable effort.

However we do then go to prolotherapy as a suggestion if these mechanisms have failed. There is a challenge with prolotherapy in that it's typically not covered by third party payers. We have a modest fee structure in our clinic that is within reach for many. But that does weigh on a patient's decision. It does influence patient's decision whether or not to opt for prolotherapy.

And so, basically, I see prolotherapy as something that is not necessarily the very first thing that we do but something that is suggested after one or two conservative treatments have not been effective.

DJ Kennedy: Do you see any role in prolotherapy being used in conjunction with some of the other treatments? For instance in a lot of musculoskeletal conditions we frequently do a treatment mainly to decrease their pain to facilitate their enrollment in physical therapy or some of these other treatments. Do you this as stand-alone or could it be used in conjunction with eccentric training?

David Rabago: You know it's a great question. And the clinical trials to date for tennis elbow have mainly been done as stand-alone therapy. But my hypothesis would be that it is – that prolotherapy would be optimized when seen as a piece of a larger treatment package, for example in the initial tennis elbow prolotherapy study on this by Scarpone and in this study that we are talking about today we did not have a physical therapy training component. And I really wonder about the loss of two things. Number one the probably salutary effects on tissue degeneration offered by eccentric exercise but also basic strength training.

There is this – with this use comes some inevitable weakness and I think part of the function component would be improved by concomitant PT. This has actually been tested not for tennis elbow but for Achilles tendinopathy by my colleague Michael Yellin in Australia. And they did an assessment of prolotherapy with and without eccentric training. And although it is a pilot study as well they found that there were some outcome measures in which the combined group, that is the prolo plus the exercise, did the best compared to either one alone.

So I think that's probably the future for optimal use of prolotherapy. But that idea hasn't been tested really in a robust trial. There is one ongoing trial for tennis elbow that do some of that also out of Australia that's enrolling participants now.

DJ Kennedy: Wonderful. We will be looking forward to those results.

David Rabago: Yes.

DJ Kennedy: I did want to go into a little bit of the details of your study and get your thought processes in some of the outcomes.

David Rabago: Yes.

DJ Kennedy: First was everyone had ultrasound and MRI and the paper appropriately this with the results and ultrasound results will be coming out in another paper which we all will anticipate the results of. The MRI was done on a 0.2 teflon magnet MRI but it did show no difference.

And part of my question is do you think that that was a sensitive enough test with a 0.2 teflon magnet MRI or is there no change in structural anatomy which we know is the case in a lot of musculoskeletal conditions despite a resolution of pain. What are your thoughts on that?

David Rabago: Yes. That is a great question. And sort of the Holy Grail of some of these assessments. I mean the new model really is that there is a degenerative element to these overused tendinopathies whereas the old model featured inflammation as the primary cause of pain and dysfunction, we now identify a tissue degeneration with or without some early especially inflammation.

And so, with that idea you – it begs the question. If there is degeneration at the outset can you do a therapy that results in improved pain and function as self-reported or volitional outcomes but then nail that down with objective evidence of tissue degeneration or tissue improvement on some visual objective measure. That's why we went after this and we followed up again on Michael Scarpone's earlier study which while showing everyone's baseline tissue dysfunction or degeneration and subsequent real improvement with prolotherapy, did not show changes in MRI.

We likewise had the same outcome. We had all subjects showing some grade of degeneration and tissue change at baseline but a mixed essentially non-responsive 16-weeks with 0.2 teflon MRI. So two issues one duration. This is a 16-week assessment and that's pretty short. The earlier study also had a 16-week outcome and similarly weak magnet. The other issue is data variability in such a small sample. This was essentially 10 elbows per group. Dr. Scarpone's earlier study was also 10 per group. And it maybe that there is simply too much variability in the response.

It's not clear to me that we aren't seeing a tissue change, that is absence of evidences is in this case not necessarily evidence of absence. But we are not certainly not detecting it with MRI in these two studies.

DJ Kennedy: You perfectly set up the next question.

David Rabago: .

DJ Kennedy: Yes. In terms of the variability within the groups. When we look at the satisfaction outcomes, and people reporting very satisfied or not satisfied it almost appears to be a bi-modal distribution of they either loved it or they were neutral to not liking it which suggests responders and non-responders and it does call in a question the use of mean data.

But the more important question in my mind for you is when I look at the MRI scores we see everything from mild to severe which is a full thickness tear. Do you think that like most musculoskeletal conditions there are clearly responders and non-responders, do you think that there is an anatomic basis for who might respond and not respond or thought process from that perspective in terms of severity in lesion or or anything else that might predict that?

David Rabago: There is certainly maybe. These data – there are too few data points, too few subjects to begin to parse that. Clinically we see tennis elbow as a result of any number of different insults and it – from a basic science perspective there certainly is some writing that suggests that tennis elbow is really – it's kind of umbrella term for insults of a variety of different tissues. Even though the elbow is quite a discreet anatomical site there still are numerous different tissues, there are numerous levels in which there are no susceptors and other agents influencing both pain and function.

I think it's completely possible that with a larger clinical trial we see the responders and non-responders break a long some discernible marker which would be of course ideal. It would be terrific to be able to know at baseline some aspect of the presenting condition that predicts response. We don't have that for tennis elbow. I've tried to do that in other studies. A knee arthritis paper was published this last summer, 2013 in Annals of Family Medicine and a follow-up paper is trying to break out responders from none and proving challenging even with a sample size of 30 per arm. So this is what we would love to do. We are not able to break that out yet.

DJ Kennedy: Our last question as we are coming to the end is this was your pilot study and you – we've gone over some of the difficulties in this group in actually predicting responders or non-responders. What do you see as the next step? I mean where are you going with it? Where does the scientific world need to take this to offer better treatments for our patients?

David Rabago: Yes. It's a terrific question. And from inside of the – I mean I'm a clinician and a researcher. And so, clinically we say boy we really need to know more. And in the mean time we'll use this information best we can with our patients. It seems to work. It seems to be safe. The patients seem to like it. But we need to know more. So when I put on my research hat I say okay let's take this to the next scientific level. And in this country that is sort of an external granting agencies such as NHI, the National Institute of Health.

Well we have submitted grants to the NHI. In my mind perfectly respectable grants. But they've not met with evaluations and quality scores that meet funding criteria levels.

DJ Kennedy: It is truly a challenging time to stay funded through the NHI grants with budget cuts.

David Rabago: Amen to that. However, that doesn't mean that science doesn't deserve to go forward. And so, I'm happy to say that these just as Michael Scarpone's initial data served as feeder data or pilot data for the paper were discussing today, my data has served as pilot feeder information, methodological strategy and so on for the study I referred to earlier at Griffith University in Australia. And that is also not funded at the national level but it is a university-based study that is designed to be a little definitive than this one both methodologically and in some of the design elements.

And let's see Michael Ryan one of the co-authors on the paper was discussing today is one of the on-site investigators in that file. ?

DJ Kennedy: Well, thank you, Doctor.

David Rabago: Sure.

DJ Kennedy: Thank you very much, Dr. Rabago. We're wrapping up our time just in respect for everyone's time for this. This was an excellent discussion and I encourage all our listeners to go read this article. It does offer insight and it's exciting and there are a whole host of articles on the American Journal of PMR that are available to be read as well.

On behalf of the Association of Academic of Academic Physiatrists we'd like to thank you for listening to this podcast. More information on the podcast from the American Journal of PMR including the journal iPod app can be found at the AAP website at . This includes today's program.

Thank you very much for your time and have a wonderful day.

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