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Clinical Trial
. 2024 Aug 13;21(8):e1004440.
doi: 10.1371/journal.pmed.1004440. eCollection 2024 Aug.

Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL)

Christelle Nguyen  1   2   3 , Emmanuel Coudeyre  4 , Isabelle Boutron  1   5   6 , Gabriel Baron  5 , Camille Daste  1   2   6 , Marie-Martine Lefèvre-Colau  1   2   7   8 , Jérémie Sellam  9   10 , Jennifer Zauderer  2 , Francis Berenbaum  9   10 , François Rannou  1   2   3
Affiliations
Clinical Trial

Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL)

Christelle Nguyen et al. PLoS Med. .

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.

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Conflict of interest statement

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.

Figures

Fig 1
Fig 1. Enrolment, randomization, and follow-up.
Fig 2
Fig 2. Distribution of numeric rating scale knee pain intensity (0–100) at baseline, 3 and 6 months (n = 71 in resveratrol group and n = 71 in placebo group at baseline, n = 67 and n = 68 at 3 months, n = 60 and n = 66 at 6 months).
The scale is an 11-point numeric rating scale in 10-point increments (0, no pain, to 100, maximal pain).
Fig 3
Fig 3. Cumulative percentage of responders with relative change in numeric rating scale score for knee pain at 3 months.
At 3 months, data were available for 67 participants in the resveratrol group and 68 in the placebo group.
See this image and copyright information in PMC

References

    1. Palazzo C, Ravaud JF, Papelard A, Ravaud P, Poiraudeau S. The burden of musculoskeletal conditions. PLoS ONE. 2014;9(3):e90633. doi: 10.1371/journal.pone.0090633 . - DOI - PMC - PubMed
    1. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377(9783):2115–26. Epub 2011/06/21. doi: 10.1016/S0140-6736(11)60243-2 . - DOI - PubMed
    1. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–89. Epub 2019/07/07. doi: 10.1016/j.joca.2019.06.011 . - DOI - PubMed
    1. Fernandes L, Hagen KB, Bijlsma JW, Andreassen O, Christensen P, Conaghan PG, et al. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis. 2013;72(7):1125–35. Epub 2013/04/19. doi: 10.1136/annrheumdis-2012-202745 . - DOI - PubMed
    1. Zeng C, Doherty M, Persson MSM, Yang Z, Sarmanova A, Zhang Y, et al. Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data. Osteoarthritis Cartilage. 2021;29(9):1242–51. Epub 2021/06/27. doi: 10.1016/j.joca.2021.06.004 . - DOI - PubMed

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