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The objective of this short communication is to demonstrate the feasibility and effectiveness of multiple placebos to individualise treatment when using classical Ayurveda for rheumatoid arthritis in well controlled, double-blind, placebo-controlled trials.
A total of 46 patients ≥18 years of age, with active rheumatoid arthritis as diagnosed using American College of Rheumatology criteria, were randomised to 1 of 3 outpatient treatment groups: methotrexate+placebo Ayurveda; Ayurveda+placebo methotrexate; and methotrexate+Ayurveda. The Ayurvedic doctor was free to choose from 148 formulations, which were in the form of 6 traditional dosage forms: decoctions, herbal powders, pills, herbal wines, herbal jams and herb-infused oils. Six placebos were also formulated, with each placebo representing a dosage form.
All appropriate institutional review board approvals were obtained. Formulations were all within US Food and Drug Administration (FDA) standards for safety. Patients were seen by allopathic and Ayurvedic doctors once every 2 weeks for 36 weeks, when physical exams, rheumatoid arthritis evaluations, and safety and efficacy studies were performed. The allopathic doctor performed all evaluations for efficacy and toxicity. At the termination visit, patients and doctors (allopathic and Ayurvedic) were separately asked to guess which regimen the patients were on during the trial.
Pearson's χ2 significance tests determined associations between the actual treatment received and those guessed to be the treatment group to which the patient was assigned. A p value of <0.05 was deemed statistically significant.
Results of the blinding are reported below (table 1) for all 46 subjects at termination, including 3 patients who discontinued at 24 weeks due to peripheral neuropathy (methotrexate arm), fractured femur (Ayurveda arm) and pregnancy (Ayurveda arm). Results showed that the double-blind procedure was successful and blinding was maintained.
There were concerns that toxicity from methotrexate might unblind the use of this medication. However, unblinding did not occur with respect to adverse events (data not shown due to space limitations).
This study is the first attempt to develop and use placebos of the traditional dosage forms of Ayurvedic pharmacological medicine in a double-blind, placebo-controlled trial. The major strength of this study was that the Ayurvedic doctor was free to individualise treatment. This is of methodological importance as it addresses one of the major concerns of practitioners of Ayurvedic and other complementary and alternative medicine (CAM) modalities requiring individualisation of treatment when they participate in well controlled trials.
We used one placebo to represent all formulations within a given dosage category because there is no appreciable difference in appearance, texture or smell among different formulations within that particular category. There were, therefore, six placebos. Our results indicate that this was an effective approach.
This study makes it possible to move clinical research on Ayurveda forward because it demonstrates that it is possible to successfully develop and use placebos for multiple dosage forms of Ayurvedic pharmacological medications in a randomised, placebo-controlled, double-blind trial of classical Ayurveda, allowing individualised treatment. The study protocol may be applicable to other CAM systems that individualise treatment. This approach demonstrates in principle and practically how such systems can be tested in ways acceptable to Western standards.
We gratefully acknowledge the contributions of K G Raveendran (the Ayurvedic doctor), Late P G Sekar (the allopathic doctor), Jidesh Gopinath, Srividya Subramanian and U Indulal.
Funding This study was supported by an award from the National Center for Complementary and Alternative Medicine, NIH grant 1 R21 AT-01969 and by the Ayurvedic Trust, Coimbatore, India.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the UCLA.
Provenance and peer review Not commissioned; externally peer reviewed.
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