Ayurveda Intervention to Enhance Clinical and Biomarker Response to Orthobiologic Treatment of Chronic Knee Osteoarthritis Pain

Awardee Recipients

  • Ariana Vora, MD

    Ariana Vora, MD

    Assistant Professor of Physical Medicine & Rehabilitation, Staff Physician

    Harvard Medical School, Spaulding Rehabilitation Hospital

    Ariana Vora, MD is an Assistant Professor at Harvard Medical School, where she has served on the faculty of the Department of Physical Medicine & Rehabilitation since 2005.  Dr. Vora completed her M.D. at Mount Sinai School of Medicine and her...

  • Kathryn Hall, PhD, MPH

    Kathryn Hall, PhD, MPH

    Assistant Professor of Medicine, Associate Molecular Biologist

    Harvard Medical School, Brigham and Women’s Hospital

    Kathryn T. Hall, PhD, MPH, is an Associate Molecular Biologist in the Division of Preventive Medicine at Brigham and Women’s Hospital and an Instructor in Medicine at Harvard Medical School (HMS).  She received her PhD in Microbiology and...


Award

  • 2019 - Pilot Grant

Background and Significance

Chronic musculoskeletal pain is a growing burden on humanity and the health care system.1 Knee osteoarthritis is becoming increasingly prevalent with the aging population, resulting in decreased physical activity, pain-related suffering, and increased cost and risk of total knee replacement and joint revision surgeries. Many medications for chronic pain, e.g. opioids, have limited efficacy, are poorly tolerated, and
have significant adverse effects including risk of addiction. In contrast, autologous platelet-rich-plasma (PRP) has evidence of long-term efficacy with low risk of adverse effects in the treatment of osteoarthritis and tendinosis.2,3 PRP contains high concentrations of growth factors, including vascular endothelial growth factor, transforminggrowth factor beta, epidermal growth factor, fibroblast growth factor, and platelet-derived growth factor.4,5 These growth factors promote local angiogenesis, inhibit pro-inflammatory cytokines, and recruit local stem cells and fibroblasts to damaged sites. Injecting injured or damaged tissue with PRP induces an endogenous
reparative cascade that results in pain relief and functional improvement.6 7 Platelets have an average lifetime of 7–10 days during which they are influenced by hormones and neurotransmitters released in response to stress (glucocorticoids and catecholamines) or relaxation (nitric oxide).8 Smoking, alcohol, and elevated blood sugar also affect platelet activation and aggregation and are thought to reduce efficacy of PRP.9 Therefore this 14-day Ayurveda regimen, designed to enhance physiologic response to treatment, has the potential to modulate platelet responsivity in this time frame.

Specific Aims

In this pilot randomized clinical trial, we will examine the effects of a 14-day Ayurveda intervention on clinical response to PRP treatment in individuals with painful knee osteoarthritis. Western Ontario McMaster Arthritis Checklist (WOMAC) scores will be the primary outcome measure to indicate clinical status and improvement in the setting of knee osteoarthritis. Additional validated questionnaires to be used as secondary clinical outcome measures are the visual analog scale (VAS) for pain and the PROMIS-10 (10 items that assess general domains of health and functioning including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life).
Biological markers in whole blood samples from participants at baseline and after the 14-day intervention will also be evaluated. Because of limited funding we have selected 3 key measures of platelet and blood function: 1) complete blood count (CBC) which includes several platelets measures; 2) levels of the pro-inflammatory cytokine IL-6; and 3) RNA sequencing to determine changes in the whole transcriptomes of peripheral blood mononuclear cells (PBMCs).

We aim to determine the following:
1. Is the Ayurveda intervention feasible such that this study can be executed on a larger scale?
2. Does the combination of the 14-day Ayurveda intervention with PRP treatment result in improved WOMAC scores when compared with PRP treatment alone? If so, does it produce responses that could feasibly be powered for a larger study?
3. Does the 14-day Ayurveda group demonstrate specific changes in CBC, IL-6, and gene expression in PBMCs? If so, do each of these responses separately correlate with improved WOMAC scores? 3

Our primary clinical outcome measure is the WOMAC scale. Given the small size of this pilot clinical trial, with ten experimental subjects and 10 control subjects, we do not expect to see statistically significant differences in WOMAC scores between the Ayurveda vs. wait-list groups. In a previous study, the WOMAC response within
each subject group was normally distributed with standard deviation 11.17, and a change of 16% in that score was considered clinically significant.10 If the true difference in the experimental and control means is 11.63, as observed in the previous study, we will be able to reject the null hypothesis that the population means of the
experimental and control groups are equal with probability (power) of 0.60. The Type I error probability associated with testing this null hypothesis is 0.05.To increase the probability (power) to 0.80, we would need to enroll 15 participants in the intervention group and 15 in the control group.

References

References

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