Atrophy, Inflammation, Weakness, Muscle
Conditions
Brief summary
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.
Interventions
DRUGMetformin
Individuals randomized to the metformin group will take metformin daily (up to 2grams/day) for 4 months following ACLR surgery.
OTHERPlacebo
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.
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTMicah Drummond
PRINCIPAL_INVESTIGATORMicah Drummond
University of Utah
Outcome results
None listed