Preventing Injured Knees From osteoArthritis: Severity Outcomes
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-45
SponsorBrigham and Women's Hospital
About this trial
This study is being done to find out if metformin is effective at reducing pain by delaying the onset of post-traumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) reconstruction. This research study will compare metformin to placebo. The placebo tablet looks exactly like metformin, but contains no metformin. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.
Metformin is approved by the U.S. Food and Drug Administration (FDA) to treat type II diabetes. Notably, it also has anti-inflammatory effects, suggesting it could benefit people who have an ACL injury and are undergoing ACL reconstruction.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 25-45 or Age 18-24 with preoperative KOOS Pain <80 (0-100, 100 best) recorded at least 14 days after the day of ACL injury
Plan to undergo ACL reconstruction within 12 months of injury
Disqualifiers
Inflammatory arthritis
Pregnancy and/or lactation, or plans to become pregnant in the next 12 months
Known contraindication to metformin
Current use of metformin or topiramate
Trial design
Design model
Parallel
Treatments tested in this trial
Metformin
DrugMetformin is an oral anti-hyperglycemic agent widely used as first-line treatment for type II diabetes to improve glycemic control. It is the fourth most commonly prescribed drug in the United States. Participants will receive commercially available extended-release metformin 500mg tablets manufactured by Granules India Limited, Hyderabad, India and then sourced, packaged, and labeled for the study by Sharp Labs. The study will follow standard dosing procedures for extended-release metformin. Participants will begin by taking 1x500 mg pill once a day, and then the dose will be increased in 500 mg/day increments every 5 days as tolerated, up to a maximum dose of 1500 mg daily.
Placebo
DrugThe study will use matching placebo tablets that are almost indistinguishable from the 500 mg metformin ER tablets. Participants will begin by taking 1x500 mg pill once a day, and then the dose will be increased in 500 mg/day increments every 5 days as tolerated, up to a maximum dose of 1500 mg daily.
Treatment groups
512 Participants
are divided into 2 treatment groupsGroup A: MetforminExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
KOOS Pain Score
To determine whether metformin leads to reduced pain as measured by the KOOS pain subscale compared to placebo between 12 and 24 months postoperatively. Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire designed to assess short and long-term patient-relevant outcomes following knee injury. The KOOS pain subscale contains 9 items and is scored on a 0-100 scale, 100 being best.
Time frame
Average of 12 and 24 months2
Modified MOAKS Cartilage Score
To determine whether metformin leads to reduced structural degeneration at 24 months postoperatively compared to placebo. The MOAKS score (MRI Osteoarthritis Knee Score) is a semi-quantitative whole joint assessment of knee osteoarthritis with very good to excellent reliability used to score knee osteoarthritis. In MOAKS the knee is divided into 14 articular subregions for scoring articular cartilage and bone marrow lesions (BMLs) and in addition the subspinous region is added for BML scoring. For each region, the following features are assessed independently: 1. bone marrow lesions and cysts (score: 0-3, 3 worst) 2. articular cartilage loss (score: 0-3, 3 worst) 3. osteophytes (score: 0-3, 3 worst) 4. synovitis and effusion (score: 0-3, 3 worst) 5. meniscus extrusion and morphology (score: 0-3, 3 worst) 6. ligaments/tendon (0/1, 0=normal, 1=abnormal) 7. periarticular features (0/1, 0=absent, 1=present)
Time frame
24 monthsSecondary outcomes
1
KOOS Pain
Assessed via questionnaire. Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire designed to assess short and long-term patient-relevant outcomes following knee injury. The KOOS is self-administered and includes 42 items across 5 subscales: pain, symptoms, ADLs, sports/recreation, and quality of life. KOOS is scored on a 0-100 scale, 100 being best. The pain subscale contains 9 items.
Time frame
baseline, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months2
KOOS Symptoms
Assessed via questionnaire. Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire designed to assess short and long-term patient-relevant outcomes following knee injury. The KOOS is self-administered and includes 42 items across 5 subscales: pain, symptoms, ADLs, sports/recreation, and quality of life. KOOS is scored on a 0-100 scale, 100 being best. The symptoms subscale contains 7 items.
Time frame
baseline, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months3
KOOS Activities of Daily Living (ADL)
Assessed via questionnaire. Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire designed to assess short and long-term patient-relevant outcomes following knee injury. The KOOS is self-administered and includes 42 items across 5 subscales: pain, symptoms, activities of daily living (ADLs), sports/recreation, and quality of life. KOOS is scored on a 0-100 scale, 100 being best. The ADL subscale contains 17 items.
Time frame
baseline, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months4
KOOS Sport and Recreation Function
Assessed via questionnaire. Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire designed to assess short and long-term patient-relevant outcomes following knee injury. The KOOS is self-administered and includes 42 items across 5 subscales: pain, symptoms, ADLs, sports/recreation, and quality of life. KOOS is scored on a 0-100 scale, 100 being best. The sports and recreation subscale contains five items.
Time frame
baseline, 3 months, 6 months, 9 months, 12 months, 18 months, 24 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Brigham and Women's Hospital
Lead sponsor
Arthritis Foundation
Collaborator
Source ClinicalTrials.gov