Metformin and ACLR Muscle Recovery

• Metformin (Drug): Individuals randomized to the metformin group will take metformin daily (up to 2grams/day) for 4 months following ACLR surgery.
• Placebo (Other): Individuals randomized to the placebo will take the same number of pills as the metformin group daily over a 4 month period following ACLR surgery.

Primary outcomes

• Thigh Muscle Fibrosis [Measured at 4 months after ACLR surgery]: Muscle collagen content (% Sirius Red Stain) will be measured in muscle biopsy samples from the involved thigh after 4 months of treatment and compared between the metformin and placebo groups.
• Thigh Muscle Cellular Senescence [Measured at 4 months following ACLR surgery.]: Muscle cellular senescence (% SA Beta galactosidase) will be measured in muscle biopsy samples from the involved thigh after 4 months treatment and will be compared between the metformin and placebo groups
• Knee extensor muscle strength [Measured at 4 months following ACLR surgery]: Knee extensor muscle strength from the involved leg (maximal voluntary isometric contraction; force) will be measured using an isokinetic dynamometer after 4 months of treatment and compared between the metformin and placebo groups.

Sex: All, ages: 40 Years to any

Inclusion Criteria:

1. Age between 40y and older
2. BMI: <30 kg/m2
3. Full thickness ACL tear
4. Less than 6 months between ACL injury and scheduled ACLR

Exclusion Criteria:

1. Prior ACL tear in limb scheduled for reconstruction or current bilateral ACL tear
2. Total knee dislocation
3. Anticipated quadriceps ACLR grafts
4. Current infection near the lower limb
5. Inability to attend physical therapy sessions
6. Post-operative loading restrictions
7. History of cardiovascular disease (e.g., CHF, CAD, MI, CVA)
8. History of endocrine or metabolic disease such as hypo/hyperthyroidism and diabetes (Treated hypo/hyperthyroid for at least 6 months will be permitted)
9. History of stroke with motor disability
10. History of respiratory disease (acute upper respiratory infection, history of chronic lung disease)
11. Self-reported pregnancy
12. Bleeding disorder
13. Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
14. Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
15. Chronic systemic corticosteroid use (≥ 2 weeks) within 4 weeks of enrollment and for study duration (intra-articular/topical/inhaled therapeutic or physiologic doses of corticosteroids will be permitted)
16. Androgens or growth hormone within 6 months of enrollment and for study duration (topical physiologic androgen replacement will be permitted)
17. Currently taking estrogen products (topical estrogen products will be permitted)
18. Taking anticoagulant medication (warfarin/Coumadin, heparin) that may complicate the muscle biopsy
19. Any staff members who report directly to the principal investigators

• Micah Drummond, Principal investigator, University of Utah