Resveratrol in Knee Osteoarthritis (ARTHROL)

Evolution of Pain at Three Months by Oral Resveratrol in Primary Knee Osteoarthritis: a Multicenter, Double-blind, Randomized, Placebo-controlled Trial

The purpose of this study is to determine whether resveratrol is effective in the treatment of painful knee osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: oral resveratrol; Drug: oral placebo

Detailed Description

Osteoarthritis (OA) is the first cause of handicap in individuals over 40 years-old in France. OA physiopathology is driven in part by local joint inflammation responsible for pain and joint destruction. Experimental studies have shown that resveratrol, a molecule antagonist to the aryl hydrocarbon receptor, has anti-inflammatory and chondroprotective properties in vitro and in vivo. The investigators hypothesize that oral resveratrol, in a new formulation improving its bioavailability, could reduce knee pain at 3 months as compared with placebo in people with knee OA.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Cébazat, France, 63118
    • Rehabilitation department , CHU Clermont-Ferrand
  • Paris
    • Paris, Paris, France, 75014
      • Rehabilitation Department, Cochin Hospital
    • Paris, Paris, France, 75012
      • Rheumatology Department, Saint Antoine Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 40 years-old
• Knee osteoarthritis fulfilling 1986 American College of Rheumatology (ACR) criteria
• Pain on numeric rating scale ≥ 40/100
• Symptom duration ≥ 1 month
• Kellgren and Lawrence X-Ray score 1, 2 or 3
• Written consent obtained
• Health insurance cover

Exclusion Criteria:

• History of symptomatic crystal or inflammatory arthritis
• Knee surgery ≤ 1 year
• Knee trauma ≤ 2 months
• Knee intra-articular injections of corticosteroids and/or hyaluronic acid ≤ 2 months
• Neurologic disorders involving the lower limbs
• Patient not understanding and not speaking french
• Participation in another biomedical research
• Contraindication to resveratrol or hypersensitivity to any of its constituents
• Current use of intramuscular, intravenous or oral corticosteroids
• Uncontrolled diseases that may require intramuscular, intravenous or oral corticosteroids
• Current use of anticoagulants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral resveratrol; Resveratrol will be administered orally, at the dose of 40 mg (2 caplets) twice a day for one week, then at the dose of 20 mg (1 caplet) twice a day, for a total duration of 6 months.	Drug: oral resveratrol; Resveratrol will be administered orally, at the dose of 40 mg (2 caplets) twice a day for one week, then at the dose of 20 mg (1 caplet) twice a day, for a total duration of 6 months.
Placebo Comparator: Oral Placebo; Placebo will be administered orally : 2 caplets twice a day for one week, then 1 caplet twice a day, for a total duration of 6 months.	Drug: oral placebo; Placebo will be administered orally : 2 caplets twice a day for one week, then 1 caplet twice a day, for a total duration of 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in knee pain in the previous 48 hours	Using a self-administered 11-point pain numeric rating scale, with 0 = no pain and 100 = maximal pain	at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in knee pain in the previous 48 hours	Using a self-administered 11-point pain numeric rating scale, with 0 = no pain and 100 = maximal pain	at 6 months
Mean change from baseline in specific activity limitation	Using self-administered WOMAC function subscore, with 0 = no	at 3 months
Mean change from baseline in specific activity limitation	Using self-administered WOMAC function subscore, with 0 = no	at 6 months
Mean change from baseline in patient's global assessment	Using a self-administered 11-point global assessment numeric rating scale, with 0 = worst possible and 100 = best possible	at 3 months
Mean change from baseline in patient's global assessment	Using a self-administered 11-point global assessment numeric rating scale, with 0 = worst possible and 100 = best possible	at 6 months
Proportion of OARSI-OMERACT responders	OARSI-OMERACT response	at 3 months
Proportion of OARSI-OMERACT responders	OARSI-OMERACT response	at 6 months
Number of intra-articular injections of corticosteroids or hyaluronic acid since last contact	using self-reporting	at 3 months
Number of intra-articular injections of corticosteroids or hyaluronic acid since last contact	using self-reporting	at 6 months
Self-reported consumption of analgesics (non-opioid, weak and strong opioids) since last contact	using a self-administered 4-class scale (never, several times a month, several times a week, daily)	at 3 months
Self-reported consumption of analgesics (non-opioid, weak and strong opioids) since last contact	using a self-administered 4-class scale (never, several times a month, several times a week, daily)	at 6 months
Self-reported consumption of non-steroidal anti-inflammatory drugs since last contact	using a self-administered 4-class scale (never, several times a month, several times a week, daily)	at 3 months
Self-reported consumption of non-steroidal anti-inflammatory drugs since last contact	using a self-administered 4-class scale (never, several times a month, several times a week, daily)	at 6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Director: Christelle NGUYEN, MD, PhD, Université Paris Descartes, PRES Sorbonne Paris Cité

Publications and helpful links

General Publications

• Nguyen C, Boutron I, Baron G, Coudeyre E, Berenbaum F, Poiraudeau S, Rannou F. Evolution of pain at 3 months by oral resveratrol in knee osteoarthritis (ARTHROL): protocol for a multicentre randomised double-blind placebo-controlled trial. BMJ Open. 2017 Sep 29;7(9):e017652. doi: 10.1136/bmjopen-2017-017652.
• Nguyen C, Coudeyre E, Boutron I, Baron G, Daste C, Lefevre-Colau MM, Sellam J, Zauderer J, Berenbaum F, Rannou F. Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL). PLoS Med. 2024 Aug 13;21(8):e1004440. doi: 10.1371/journal.pmed.1004440. eCollection 2024 Aug.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2017
• Primary Completion (Actual): February 9, 2022
• Study Completion (Actual): May 12, 2022

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimated): September 19, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Osteoarthritis; Pain; Knee; Trial; Oral Treatment; Resveratrol
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Osteoarthritis; Osteoarthritis, Knee; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Stilbenes; Benzylidene Compounds; Stilbestrols; Polyphenols; Resveratrol
• Other Study ID Numbers: P150938; 2016-A01310-51 (Registry Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No