Metformin and ACLR Muscle Recovery

Early Phase 1Not Yet RecruitingNCT07699367

University of Utah40 enrolled

Overview

The purpose of this research study is to determine if Metformin taken after anterior cruciate ligament reconstruction (ACLR) surgery can decrease muscle fibrosis, cellular senescence and improve leg strength. ACL injury and surgery increase muscle collagen content and inflammation which slows the recovery of muscle and function and ultimately impacts the quality of life. Individuals enrolled in the study will be randomized to receive metformin (or placebo) for 4 months after surgery. The investigators will measure muscle strength and inflammatory markers in muscle biopsy samples after the intervention period. Investigators will also follow up with participants 8 months later to determine the lasting effects of the intervention.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Atrophy Inflammation Weakness, Muscle

Interventions

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Thigh Muscle Fibrosis

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.

Time frame: Measured at 4 months after ACLR surgery

Thigh Muscle Cellular Senescence

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

Time frame: Measured at 4 months following ACLR surgery.

Knee extensor muscle strength

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.

Time frame: Measured at 4 months following ACLR surgery