None listed
Conditions
Brief summary
Osteoarthritis is a leading cause of disability with no cure. Current therapies are limited, with end-stage osteoarthritis treated with costly total joint replacement. There is an urgent unmet need for an effective disease-modifying drug to reduce the burden of the disease. Obesity and obesity-related metabolic and inflammatory factors are risk factors for knee osteoarthritis with people with osteoarthritis at increased risk of cardiovascular disease morbidity and mortality. Metformin, a safe, low-cost, well-tolerated first-line therapy for type 2 diabetes for over 60 years, affects these pathways with evidence from animal and human studies that metformin may reduce pain of knee osteoarthritis and reduce cardiovascular risk. We propose to test this in a randomised double-blind placebo-controlled trial in participants with knee osteoarthritis and obesity. AIMS: To determine whether metformin reduces knee pain over 6 months compared with placebo in people with knee osteoarthritis who are obese. PARTICIPANTS: 102 participants with knee osteoarthritis and obesity INTERVENTION: Metformin (2000 mg) once daily COMPARATOR: Identical placebo once daily OUTCOME: Change in knee pain assessed by visual analogue scale at 6 months SIGNIFICANCE: The repositioning of metformin, a cheap, safe, old drug for this new indication, offers an unprecedented opportunity to significantly and immediately impact the management of osteoarthritis in Australia and worldwide. It has very high potential for rapid translation being a safe, easy to use medication with medical practitioners who have repeatedly called for effective treatments for knee osteoarthritis familiar with its use. Metformin has the potential to significantly reduce disease burden and healthcare costs, while improving quality of life and reducing cardiovascular risk in people with knee osteoarthritis.
Interventions
Metformin (oral tablet, up to 2000 mg) once daily over 6 months
Study medication will be initiated at a dose of 500 mg once daily with the evening meal for 2 weeks. The dose will be increased by 500 mg every 2 weeks. Over 6 weeks, the dose of study medication will be titrated to 2000 mg once daily.
Adherence to study medication will be assessed by bottle returns and pill count.
Sponsors
Flavia Cicuttini
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women aged over 40 years, with overweight or obesity (body mass index greater than or equal to 25 kg/m2); 2. Knee pain for at least 6 months with a pain score greater than or equal to 40 mm on a 100 mm visual analogue scale (VAS); 3. Meet the American College of Rheumatology clinical criteria for knee osteoarthritis.
Exclusion criteria
1. Severe radiographic knee osteoarthritis (Kellgren-Lawrence grade 4) or severe knee pain (on standing >80 mm on a 100 mm VAS); 2. Any inflammatory arthritis or significant knee injury; 3. Known or newly diagnosed diabetes requiring anti-hyperglycemic therapy or previous adverse reaction to metformin; 4. Index knee surgery (arthroscopy or open surgery) in the past year; 5. Index knee intra-articular hyaluronic acid injection in the past 6 months or corticosteroid injection in the past 3 months; 6. Use of any investigational drugs or device within 30 days prior to randomisation; 7. Index knee planned joint replacement or arthroscopy in the next 6 months; 8. Other muscular, joint or neurological condition affecting lower limb function; 9. Acute or chronic renal or liver impairment; 10. Other medical condition precluding study participation or relocation; 11. Women who are pregnant, lactating or trying to become pregnant. Use of menopausal hormone therapy or oral contraceptive pill will be permitted so long as the dose has been stable for at least 30 days prior to study entry.
Outcome results
None listed