1. Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL).
- Author
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Nguyen C, Coudeyre E, Boutron I, Baron G, Daste C, Lefèvre-Colau MM, Sellam J, Zauderer J, Berenbaum F, and Rannou F
- Subjects
- Humans, Male, Female, Middle Aged, Double-Blind Method, Administration, Oral, Aged, Treatment Outcome, Pain Measurement, France, Adult, Osteoarthritis, Knee drug therapy, Osteoarthritis, Knee complications, Resveratrol administration & dosage, Resveratrol therapeutic use
- Abstract
Background: Resveratrol is a natural compound found in red wine. It has demonstrated anti-inflammatory properties in preclinical models. We compared the effect of oral resveratrol in a new patented formulation to oral placebo for individuals with painful knee osteoarthritis., Methods and Findings: ARTHROL was a double-blind, randomized, placebo-controlled, Phase 3 trial conducted in 3 tertiary care centers in France. We recruited adults who fulfilled the 1986 American College of Rheumatology criteria for knee osteoarthritis and reported a pain intensity score of at least 40 on an 11-point numeric rating scale (NRS) in 10-point increments (0, no pain, to 100, maximal pain). Participants were randomly assigned (1:1) by using a computer-generated randomization list with permuted blocks of variable size (2, 4, or 6) to receive oral resveratrol (40 mg [2 caplets] twice a day for 1 week, then 20 mg [1 caplet] twice a day; resveratrol group) or matched oral placebo (placebo group) for 6 months. The primary outcome was the mean change from baseline in knee pain on a self-administered 11-point pain NRS at 3 months. The trial was registered at ClinicalTrials.gov: (NCT02905799). Between October 20, 2017 and November 8, 2021, we assessed 649 individuals for eligibility, and from November 9, 2017, we recruited 142 (22%) participants (mean age 61.4 years [standard deviation (SD) 9.6] and 101 [71%] women); 71 (50%) were randomly assigned to the resveratrol group and 71 (50%) to the placebo group. At baseline, the mean knee pain score was 56.2/100 (SD 13.5). At 3 months, the mean reduction in knee pain was -15.7 (95% confidence interval (CI), -21.1 to -10.3) in the resveratrol group and -15.2 (95% CI, -20.5 to -9.8) in the placebo group (absolute difference -0.6 [95% CI, -8.0 to 6.9]; p = 0.88). Serious adverse events (not related to the interventions) occurred in 3 (4%) in the resveratrol group and 2 (3%) in the placebo group. Our study has limitations in that it was underpowered and the effect size, estimated to be 0.55, was optimistically estimated., Conclusions: In this study, we observed that compared with placebo, oral resveratrol did not reduce knee pain in people with painful knee osteoarthritis., Trial Registration: ClinicalTrials.gov ID: NCT02905799., Competing Interests: CN is an Academic Editor on PLOS Medicine’s editorial board. She reports receiving consulting fees from Thuasne, Merz and Ipsen; speaker fees from Actelion Pharmaceuticals France, Ipsen, Lilly, Meda pharma and Novartis; reimbursement of conference registration and accommodation by Grünenthal and Merz; and hospitality from Preciphar, Sandoz, Takeda France, and UCB Pharma SA, outside of the submitted work (<$5,000/y). CD reports receiving hospitality from Merz, outside of the submitted work. JS reports receiving personal fees from MSD, Pfizer, Abbvie, Fresenius Kabi, BMS, Roche, Chugai, Sandoz, Lilly, Novartis, Galapagos, AstraZeneca, UCB and Janssen and research grants from Pfizer, MSD, Schwa Medico, and BMS, outside of the submitted work. FB reports receiving consulting or speaker fees from AstraZeneca, Boehringer Ingelheim, Cellprothera, Galapagos, Grünenthal, GSK, Eli Lilly, MerckSerono, Nordic Bioscience, Novartis, Pfizer, Sanofi, Servier, Peptinov, Viatris, Aché Lab. Shareholder of 4Moving Biotech and 4P Pharma, outside of the submitted work. EC, IB, GB, MMLC, JZ and FR report no conflict of interest., (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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