Use of Metformin to Improve Muscle Regrowth in Older Adults

086328

A hallmark of aging is an impaired ability to adequately recover following a stressor, such as muscle disuse, resulting in muscle fibrosis and weakness thereby increasing the risk for falls and loss of independence. Mechanistic-based therapeutic strategies to enhance muscle recovery in older adults do not exist. Metformin has been implicated to have positive effects on muscle size and function through non-glycemic mechanisms. Metformin has been shown to enhance macrophage function and lessen cellular senescence burden by targeting SASP in a variety of muscle interstitial cells. However, the role of metformin to improve muscle recovery in older adults following disuse atrophy through immunomodulating and senomorphic mechanisms have not been examined. Therefore, the purpose of this study is to conduct a randomized, double blind, placebo-controlled clinical trial in older adult participants to determine if short-term metformin delivery (vs placebo) during the recovery phase following disuse atrophy can improve muscle regrowth.

2024-09-01

2029-07-31

2030-07-31

Not yet recruiting

Early phase I

50

Inclusion Criteria: 1. Age between 60y and older 2. BMI: \<30 kg/m2 3. Good general medical health, ambulatory and in independent living setting 4. Adequate upper body strength to use assistive walking device (crutches, walker, etc) as assessed by PI/staff during screening 5. Clinical Frailty Scale score \< 3 6. Mini-Cog score \> 3 Exclusion Criteria: 1. History of cardiovascular disease (e.g., CHF, CAD, MI, CVA) 2. History of endocrine or metabolic disease such as hypo/hyperthyroidism and diabetes (Treated hypo/hyperthyroid for at least 6 months will be permitted) 3. History of kidney disease or failure (CKD \> stage 4; serum creatinine \>1.5mg/dL) 4. History of vascular disease 5. Risk of DVT including family history of thrombophilia, DVT, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb\>18 g/dL) or thrombocytosis (platelets\>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocystinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombine III 6. Use of anticoagulant therapy (e.g., Coumadin, heparin) 7. Uncontrolled hypertension - Elevated systolic pressure \>150 or a diastolic blood pressure \> 100 8. Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators) 9. Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma 10. 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) 11. Androgens or growth hormone within 6 months of enrollment and for study duration (topical physiologic androgen replacement will be permitted) 12. Inability to abstain from smoking or vaping for duration of study 13. Currently taking estrogen products (topical estrogen products will be permitted) 14. Currently on weight loss diet or medication 15. History of stroke with motor disability 16. A recent history (\<12 months) of GI bleed 17. History of liver disease or AST/ALT 2 times above the normal limit 18. History of respiratory disease (acute upper respiratory infection, history of chronic lung disease) 19. Any staff members who report directly to the principal investigators

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '2-weeks single leg immobilization followed by 2-weeks of recovery', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'Metformin and Placebo pills will be encapsulated by the pharmacy in order to protect treatment assignment', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 50, 'type': 'ESTIMATED'}}

2024-01-03