Using metformin to reduce knee pain after ACL surgery

Preventing Injured Knees From osteoArthritis: Severity Outcomes (PIKASO)

This study is testing if metformin can help reduce knee pain and prevent arthritis in people recovering from ACL surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 512 (estimated)
• Ages: 18 Years to 45 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Locations: 9 sites (Atlanta, Georgia and 8 other locations)
• Trial ID: NCT06096259 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of metformin in reducing pain and delaying the onset of post-traumatic osteoarthritis (PTOA) following anterior cruciate ligament (ACL) reconstruction. Participants will be randomly assigned to receive either metformin or a placebo, which looks identical but contains no active medication. The study aims to determine if metformin's known anti-inflammatory properties can benefit individuals recovering from ACL injuries. By focusing on a specific age group and preoperative pain levels, the study seeks to identify those most likely to benefit from this intervention.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 18-45 who plan to undergo ACL reconstruction within 12 months of their injury and have specific preoperative pain levels.

Not a fit: Patients with inflammatory arthritis, diabetes, or significant knee damage may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option to reduce pain and improve outcomes for patients recovering from ACL injuries.

How similar studies have performed: While metformin is primarily known for diabetes management, its anti-inflammatory effects suggest potential benefits in similar contexts, though this specific application is novel.

Eligibility criteria

Inclusion Criteria:

1. 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:

1. 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, medial collateral ligament, or lateral collateral ligament injury on index knee requiring surgical repair/reconstruction
14. Contraindication to MRI
15. Unable to speak and understand English
16. Diagnosis of cognitive impairment or otherwise unable to provide informed consent
17. Insufficient time for recruitment and drug titration: Surgery scheduled for \<14 days from the time of screening
18. Date of injury more than 6-months ago, relative to date of screening
19. Presence of a condition or abnormality that in the opinion of the surgeon investigator would compromise the safety of the patient or the quality of the data
20. Plan for allograft at time of consent

Where this trial is running

Atlanta, Georgia and 8 other locations

• Emory University — Atlanta, Georgia, United States (Recruiting)
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States (Recruiting)
• University of Kentucky — Lexington, Kentucky, United States (Recruiting)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)
• Hospital for Special Surgery — New York, New York, United States (Recruiting)
• The University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
• The Ohio State University — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Morgan H Jones, MD, MPH — Brigham and Women's Hospital
• Study coordinator: Faith Selzer, PhD

Conditions Osteoarthritis, Knee; Post-traumatic Osteoarthritis; ACL Tear