Recruiting

Phase 2

Observational StudyPreventing Injured Knees From osteoArthritis: Severity Outcomes

Sponsor:

Brigham and Women's Hospital

Code:

NCT06096259

Conditions

Osteoarthritis, Knee

Post-traumatic Osteoarthritis

ACL Tear

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Not accepted

Interventions

Metformin

Placebo

Study Details

Brief summary:

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.

Conditions

Osteoarthritis, Knee

Post-traumatic Osteoarthritis

ACL Tear

Study ID

NCT06096259

Start date

May 6, 2024

Status verified date

Apr, 2025

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

512 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Metformin

3x500mg metformin hydrochloride (HCl) extended-release (ER) tablets taken orally once a day for 1 year

placebo comparator: Placebo

3x metformin placebo tablets matching metformin extended-release taken orally once a day for 1 year

Interventions

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.

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 measure

KOOS Pain Score [ Time Frame: Average of 12 and 24 months ]
Modified MOAKS Cartilage Score [ Time Frame: 24 months ]

Central Contacts and Locations

Central contacts

Faith Selzer, PhD

617-525-8617 fselzer@bwh.harvard.edu

Daniel J Betensky, AB

6175259727 dbetensky@bwh.harvard.edu

Locations

Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Principal Investigator:

Gregory D Myer, PhD

University of Iowa Hospitals and Clinics

Recruiting

Iowa City, Iowa, United States, 52242

Principal Investigator:

Don D Anderson, PhD

University of Kentucky

Recruiting

Lexington, Kentucky, United States, 40504

Principal Investigator:

Austin V Stone, MD, PhD

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Rachel Lovejoy

6177326934 rlovejoy@bwh.harvard.edu

Principal Investigator:

Morgan H Jones, MD, MPH

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

Principal Investigator:

Elizabeth A Wellsandt, PT, PhD

Hospital for Special Surgery

Recruiting

New York, New York, United States, 10021

Principal Investigator:

Scott A Rodeo, MD

The University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 25599

Principal Investigator:

Joe M Hart, PhD

Cleveland Clinic

Recruiting

Cleveland, Ohio, United States, 44195

Principal Investigator:

Kurt Spindler, MD

The Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Laura C Schmitt, PT, PhD

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Apr 29, 2025

Last verified

Apr, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2025-04-29.