The Long-term Evaluation of Glucosamine Sulphate Study (LEGS)

The Effect of Glucosamine Sulphate on Structural Disease Progression in Knee Osteoarthritis and the Cost-effectiveness of Glucosamine Sulphate for Knee Arthritis.

The primary aim of this study is to determine if the dietary supplements, glucosamine sulphate and/or chondroitin can limit or reduce structural disease progression whilst providing symptomatic benefit in people with osteoarthritis (OA) of the knee. The specific hypotheses to be tested in the proposed double blind, placebo-controlled, randomised clinical trial are that, compared to participants allocated to placebo, participants allocated to either or both of these dietary supplements will demonstrate: reduced medial tibio-femoral joint space narrowing at 2 years AND; reduced knee pain over 1 year These benefits will be achieved by participants allocated to glucosamine sulphate and/or chondroitin (the study treatments) without concomitant: increased use of analgesics reduced health-related quality of life reduced participation in leisure-time physical activity

The LEGS study is a double blind, placebo-controlled randomised clinical trial using a 2 x 2 factorial design. Participant will be randomly allocated to one of the four possible treatment combinations: Glucosamine and Chondroitin (double active) Placebo Glucosamine and Chondroitin Glucosamine and Placebo Chondroitin Placebo Glucosamine and Placebo Chondroitin (double placebo) Each allocation involves taking 4 study treatment capsules once a day for two years. A total of 600 participants with symptomatic knee OA will be recruited by general media advertising and by General Practitioners through the New South Wales Divisions of general practice.

Glucosamine: Two 750mg capsules once daily for two years; Chondroitin: Two 400mg capsules once daily for two years.

Glucosamine: Two 750mg capsules once daily for two years; Placebo Chondroitin: Two capsules once daily for two years.

Chondroitin sulphate: Two 400mg capsules once daily for two years; Placebo glucosamine: Two capsules once daily for two years.

Two placebo glucosamine capsules once daily for two years; Two placebo chondroitin capsules once daily for two years.

Inclusion Criteria: Knee pain, or taking NSAIDs/ analgesia for knee pain on most days past month Knee pain 4-10 on 10cm VAS Medial tibio-femoral compartment joint space narrowing in symptomatic knee Exclusion Criteria: Unstable diabetes <2mm medial tibio-femoral compartment joint space width

Simic M, Harmer AR, Agaliotis M, Nairn L, Bridgett L, March L, Votrubec M, Edmonds J, Woodward M, Day R, Fransen M. Clinical risk factors associated with radiographic osteoarthritis progression among people with knee pain: a longitudinal study. Arthritis Res Ther. 2021 Jun 4;23(1):160. doi: 10.1186/s13075-021-02540-9.

Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Su S, Jan S, March L, Edmonds J, Norton R, Woodward M, Day R; LEGS study collaborative group. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015 May;74(5):851-8. doi: 10.1136/annrheumdis-2013-203954. Epub 2014 Jan 6.

Laba TL, Brien JA, Fransen M, Jan S. Patient preferences for adherence to treatment for osteoarthritis: the MEdication Decisions in Osteoarthritis Study (MEDOS). BMC Musculoskelet Disord. 2013 May 6;14:160. doi: 10.1186/1471-2474-14-160.