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

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Dietary supplement: Glucosamine sulphate and chondroitin; Dietary supplement: Glucosamine sulphate; Dietary supplement: Chondroitin sulphate; Dietary supplement: Placebo capsules for glucosamine and chondroitin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 1825
      • Marlene Fransen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Glucosamine sulfate 1500mg and chondroitin sulfate 800mg (low molecular weight, bovine)	Dietary supplement: Glucosamine sulphate and chondroitin; Glucosamine: Two 750mg capsules once daily for two years; Chondroitin: Two 400mg capsules once daily for two years.; Other Names: Glucosamine; Chondroitin
Experimental: 2; Glucosamine sulfate 1500mg	Dietary supplement: Glucosamine sulphate; Glucosamine: Two 750mg capsules once daily for two years; Placebo Chondroitin: Two capsules once daily for two years.; Other Names: Glucosamine
Experimental: 3; Chondroitin sulfate 800mg	Dietary supplement: Chondroitin sulphate; Chondroitin sulphate: Two 400mg capsules once daily for two years; Placebo glucosamine: Two capsules once daily for two years.; Other Names: Chondroitin
Placebo Comparator: 4; Matching glucosamine/chondroitin placebo capsules	Dietary supplement: Placebo capsules for glucosamine and chondroitin; Two placebo glucosamine capsules once daily for two years; Two placebo chondroitin capsules once daily for two years.; Other Names: Double placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Medial tibio-femoral joint space narrowing (mm)	MRI (1 year) Radiographs (2 years)
Knee pain (11 point Likert scale)	Bimonthly for 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
WOMAC	1 year, 2 years
Patients global assessment	Bimonthly for 1 year
Total NSAIDs use	Bimonthly for 1 year
General health status (SF-12v2)	1 year, 2 years
Cost-effectiveness (cost per OMERACT-OARSI responder)	2 years
Leisure time physical activity	1 year, 2 years

Collaborators and Investigators

• Sponsor: University of Sydney
• Collaborators: National Health and Medical Research Council, Australia
• Investigators: Principal Investigator: Marlene Fransen, PhD, MPH, University of Sydney, Faculty of Health Sciences; Principal Investigator: Richard Day, MB, BS, MD, University of New South Wales; Principal Investigator: Charles Bridges-Webb, MB, BS, Royal College of General Practitioners; Principal Investigator: John Edmonds, MB,BS, University of New South Wales; Principal Investigator: Robyn Norton, PhD, MPH, The George Institute, University of Sydney; Principal Investigator: Mark Woodward, PhD, MSc, The George Institute, University of Sydney; Principal Investigator: Lynette March, PhD, MB, BS, University of Sydney; Principal Investigator: Philip Sambrook, MB, BS, Institute of Bone and Joint Research, University of Sydney

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Anticipated): October 1, 2011
• Study Completion (Anticipated): October 1, 2011

Study Registration Dates

• First Submitted: August 7, 2007
• First Submitted That Met QC Criteria: August 7, 2007
• First Posted (Estimate): August 8, 2007

Study Record Updates

• Last Update Posted (Estimate): June 30, 2010
• Last Update Submitted That Met QC Criteria: June 29, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: Disease progression; NSAIDs; Glucosamine; Chondroitin; Osteoarthritis, knee
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Disease Progression; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: GI-IM-LEGS-L; NHMRC 402511 (Other Grant/Funding Number: National Health and Medical Research Council of Australia); NHMRC 402781 (Other Grant/Funding Number: National Health and Medical Research Council of Australia)