NCT06096259 · Brigham and Women's Hospital
Preventing Injured Knees From osteoArthritis: Severity Outcomes
(PIKASO)
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Metformin
Metformin 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.
DRUG
Placebo
The 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.
Primary outcome measures
KOOS Pain Score
Time frame: Average of 12 and 24 months
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.
Modified MOAKS Cartilage Score
Time frame: 24 months
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)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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 2. Plan to undergo ACL reconstruction within 12 months of injury
Exclusion criteria
- Inflammatory arthritis 2. Pregnancy and/or lactation, or plans to become pregnant in the next 12 months 3. Known contraindication to metformin 4. Current use of metformin or topiramate 5. Diabetes mellitus or diabetic ketoacidosis 6. Acute or chronic renal insufficiency 7. History of prior ACL tear on the index knee, with or without reconstruction 8. History of ACL tear on the contralateral knee within the past 12 months 9. Applying for or receiving Workers' Compensation for their knee injury 10. Joint space narrowing AND definite osteophyte(s) on weightbearing radiograph on index knee 11. Tibial plateau fracture on index knee 12. Concomitant avulsion fracture of index knee that will be treated surgically 13. Concomitant posterior cruciate ligament
Where
- Atlanta, Georgia
- Iowa City, Iowa
- Lexington, Kentucky
- Boston, Massachusetts
- Omaha, Nebraska
- New York, New York
- Chapel Hill, North Carolina
- Cleveland, Ohio
- Columbus, Ohio
Collaborators
Arthritis Foundation
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 29, 2025 · Source of record for eligibility and locations