Role of Metformin on Muscle Health of Older Adults

NCT03107884 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 93579
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Muscle atrophy and insulin resistance are common after bed rest in healthy older adults. Metformin treatment has been shown to improve insulin sensitivity and attenuate muscle loss in insulin resistance adults though the mechanisms are not fully known. Metformin used as a preventive strategy to maintain muscle and metabolic health in bed ridden older adults has not been investigated.

Conditions

Muscle Atrophy; Insulin Resistance

Keywords

Insulin Resistance; Muscle Atrophy; Metformin; Muscle Loss; Inactivity-induced muscle loss; older adults

Outcome Measures

Primary Outcomes (2)

• Muscle size

  Change in muscle size from baseline to 5-days of bed rest (determined from MRI)

  Change in muscle size from baseline to 5-days of bed rest will be compared between groups after 5 days of bed rest

• Insulin sensitivity

  Change in insulin sensitivity from baseline to 5-days of bed rest (determined from glucose infusion rate)

  Change in insulin sensitivity from baseline to 5-days of bed rest will be compared between groups after 5 days of bed rest

Study Arms (4)

Metformin (Bed Rest)

EXPERIMENTAL

Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day). During bed rest, participants will be given 1 gram of metformin two times a day (morning and evening). This dosage and frequency will occur during four consecutive days of bed rest.

Drug: Metformin (Bed Rest)

Placebo (Bed Rest)

PLACEBO COMPARATOR

Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group. During bed rest, participants will be given the same amount of pills and given at the same time of day (morning and evening) as the experimental group. This strategy will occur during four consecutive days of bed rest.

Drug: Placebo (Bed Rest)

Metformin (2 week run-in only)

EXPERIMENTAL

Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day). These participants will not participate in the bed rest portion of the protocol.

Drug: Metformin (2 week run-in only)

Placebo (2 week run-in only)

PLACEBO COMPARATOR

Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group. These participants will not participate in the bed rest portion of the protocol.

Drug: Placebo (2 week run-in only)

Interventions

Metformin (Bed Rest) DRUG

A clinical oral dose of Metformin will be given to participant daily during bed rest

Also known as: Metformin hydrochloride, Fortamet, glucophage, Glumetza, Riomet

Metformin (Bed Rest)

Placebo (Bed Rest) DRUG

Placebo-comparator. The same quantity of non-active tablets will be given at the same time of day as the Metformin treatment group

Placebo (Bed Rest)

Metformin (2 week run-in only) DRUG

A clinical oral dose of Metformin will be given to participant daily during a two week run-in period only.

Also known as: Metformin hydrochloride, Fortamet, Glucophage, Glumetza, Riomet

Metformin (2 week run-in only)

Placebo (2 week run-in only) DRUG

Placebo-comparator. The same quantity of non-active tablets will be given at the same time of day as the Metformin 2 week run-in treatment group.

Placebo (2 week run-in only)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60y and older
• Ability to sign informed consent
• Free-living, prior to admission

You may not qualify if:

• Personal history of cardiovascular disease
• Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, HbA1c ≥6.5%)
• Evidence of kidney disease or failure (defined as serum creatinine \> 1.5mg/dL)
• Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes)
• Risk of Deep vein thrombosis including family history of thrombophilia, Deep vein thrombosis, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb\>18 g/dL) or thrombocytosis (platelets\>400x103/mL)
• Use of anticoagulant therapy (e.g., Coumadin, heparin)
• Uncontrolled hypertension (e.g. systolic pressure \>160 or a diastolic blood pressure \> 100)
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Currently on a weight-loss diet or body mass index \> 30 kg/m2
• Inability to abstain from smoking for duration of study
• HIV or hepatitis B or C\*
• Subjects excluded due to positive screening results, including HIV, hepatitis B or hepatitis C, will be immediately scheduled for counseling and follow-up testing as needed, and will be advised to consult their primary physician.
• 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 are permitted). Androgens or growth hormone within 6 months of enrollment and for study duration (topical physiologic androgen replacement is permitted)
• Subjects with hemoglobin or hematocrit lower than accepted lab values
• History of stroke with motor disability

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (3)

• Petrocelli JJ, McKenzie AI, de Hart NMMP, Reidy PT, Mahmassani ZS, Keeble AR, Kaput KL, Wahl MP, Rondina MT, Marcus RL, Welt CK, Holland WL, Funai K, Fry CS, Drummond MJ. Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment. Aging Cell. 2023 Nov;22(11):e13936. doi: 10.1111/acel.13936. Epub 2023 Jul 24.

  PMID: 37486024 DERIVED

• Petrocelli JJ, de Hart NMMP, Lang MJ, Yee EM, Ferrara PJ, Fix DK, Chaix A, Funai K, Drummond MJ. Cellular senescence and disrupted proteostasis induced by myotube atrophy are prevented with low-dose metformin and leucine cocktail. Aging (Albany NY). 2023 Mar 20;15(6):1808-1832. doi: 10.18632/aging.204600. Epub 2023 Mar 20.

  PMID: 36947713 DERIVED

• McKenzie AI, Mahmassani ZS, Petrocelli JJ, de Hart NMMP, Fix DK, Ferrara PJ, LaStayo PC, Marcus RL, Rondina MT, Summers SA, Johnson JM, Trinity JD, Funai K, Drummond MJ. Short-term exposure to a clinical dose of metformin increases skeletal muscle mitochondrial H2O2 emission and production in healthy, older adults: A randomized controlled trial. Exp Gerontol. 2022 Jun 15;163:111804. doi: 10.1016/j.exger.2022.111804. Epub 2022 Apr 9.

  PMID: 35405248 DERIVED

MeSH Terms

Conditions

Muscular Atrophy; Insulin Resistance

Interventions

Metformin; Bed Rest

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Therapeutics

Study Officials

• Micah Drummond

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: drug and placebo will be encapsulated therefore concealing the participant, investigator and outcome assessor to group assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: April 11, 2017
• Study Start: August 1, 2019
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)