Metformin as Adjuvant Therapy in Obese Knee Osteoarthritis Patients

Study Overview
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Brief Summary
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This study aims to evaluate the possible efficacy and safety of addition of metformin to celecoxib in patients with knee osteoarthritis.

Detailed Description
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Metformin is a safe, well-tolerated oral biguanide widely used as first-line therapy for type 2 diabetes for over 50 years. In addition to its glucose-lowering effects, metformin modulates inflammatory and metabolic factors resulting in weight loss and reduced inflammation and plasma lipids. Data from animal studies suggest that metformin could limit OA development and progression, possibly through activating AMPK. Retrospective cohort study of participants with OA and type 2 diabetes reported that patients receiving a combination of cyclooxygenase-2 inhibitors and metformin therapy had a lower risk of joint replacement than those receiving cyclooxygenase-2 inhibitors alone . These findings shed light on possible therapeutic potential of metformin in treatment of OA.

Official Title
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Metformin as Adjuvant Therapy in Obese Knee Osteoarthritis Patients

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: Placebo Tablet
* Drug: Metformin Hcl 500Mg Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have symptomatic and radiological evidence of OA in one or both knee joints. Age ≥ 45 years. Both obese male and female will be included (BMI ≥ 30 kg/m²). Exclusion Criteria: Patients with inflammatory rheumatic diseases, crystal deposition arthritis or infection-induced OA. Patient with hypertension or diabetes mellitus. Patient with hepatic or renal impairment. Patients who have active peptic ulcer. Patients with positive malignancy. Steroid injection into the affected knee joint within 3 months of recruitment for the study. Pregnant or lactating female patients.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo group<br>Placebo tablet twice daily + celecoxib 200mg capsule once daily for 12 weeks. | Drug: Placebo Tablet<br>* Placebo (tablet/12hr) + celecoxib (200mg/day) for three months.<br>|
| Experimental: Metformin group<br>Metformin 500mg tablet twice daily + celecoxib 200mg capsule once daily for 12 weeks. | Drug: Metformin Hcl 500Mg Tab<br>* Metformin (500mg/12hr) + celecoxib (200mg/day) for three months.<br>* Other names: Cidophage 500mg Oral Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Measure change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) at baseline and after 12weeks of treatment. | 12 weeks | 
| Weight (Kg) | Measure change in weight in kilograms at baseline and after 12weeks of treatment. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cartilage Oligomeric Matrix Protein (COMP) | Measure change in Cartilage Oligomeric Matrix Protein (COMP) serum level at baseline and after 12weeks of treatment. | 12 weeks | 
| C-terminal crosslinked telopeptide of type I collagen (CTX-1) | Measure change in C-terminal crosslinked telopeptide of type I collagen (CTX-1) serum level at baseline and after 12weeks of treatment. | 12 weeks | 
| Interleukin 1-beta (IL-1β) | Measure change in Interleukin 1-beta (IL-1β) serum level at baseline and after 12weeks of treatment. | 12 weeks | 
| Adverse drug events | side effects | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, knee osteoarthritis