Metformin to Augment Strength Training Effective Response in Seniors (MASTERS)

Aging Clinical Trial

Official title:

Novel Actions of Metformin to Augment Resistance Training Adaptations in Older Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02308228
• Other study ID #: 1R01AG046920-01A1
• Status: Completed
• Phase: Early Phase 1
• Start date: January 14, 2015
• Est. completion date: June 28, 2018

Study information

• Verified date: August 2019
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether a commonly prescribed drug, metformin, can enhance the benefits seen during resistance exercise such as increased muscle mass and strength.

Description:

Muscle mass and strength are critical determinants not only of a person's quality of life and functional independence, but also metabolic health, as muscle is the organ primarily responsible for insulin-mediated glucose uptake. The elderly suffer obligatory losses of muscle mass and strength, exacerbated by illness and physical inactivity. Progressive resistance exercise training (PRT) is the most effective intervention identified to improve muscular strength, and combat the muscle atrophy of aging (sarcopenia); however, overall the muscle response to PRT is blunted in the elderly and variability of response increased, with some individuals actually losing muscle mass. The Bamman and Peterson labs have independently been studying the molecular and cellular mechanisms underlying the "non-responder" phenotype, with the goal of identifying novel intervention strategies to promote mass and strength gains to improve function. We hypothesize that the abundance of anti-inflammatory, alternatively activated M2 macrophages in muscle predicts response to PRT in the elderly; those with the highest number of M2 macrophages and lowest inflammatory gene expression prior to the start of training gained the most mass. Further, we determined that metformin treatment increased M2 macrophage abundance, and decreased inflammatory cytokine gene expression. These provocative findings have led us to our central hypothesis that adjuvant metformin may improve the responses to PRT in the elderly by altering the muscle tissue inflammatory environment, thereby enhancing mechanisms that drive PRT-induced myofiber hypertrophy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: June 28, 2018
• Est. primary completion date: December 14, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• =65 years of age.

• Independently mobile with a SPPB score 3-12.

• Access to transportation.

• Capable of providing informed consent (cognitively intact).

Exclusion Criteria:

• Obesity (BMI>30)

• Serum creatinine >1.4 because of risk of lactic acidosis with metformin.

• History of regular resistance training within the past year.

• History (or ECG evidence) of previous myocardial infarction, history of congestive heart failure.

• Current angina pectoris or symptoms of myocardial ischemia or congestive heart failure.

• Chronic aspirin or NSAID use (unless it can be safely stopped prior to the biopsies), and any other use of an anticoagulant (e.g., Coumadin) or history of bleeding.

• History of alcoholism or liver disease.

• History of hypo- or hyper-coagulation disorders including subjects taking Coumadin.

• Any end-stage disease and/or a life expectancy less than one year.

• Neurological, musculoskeletal, or other disorder that would preclude them from completing resistance training and all performance tests.

• Uncontrolled hypertension.

• Diabetes mellitus as demonstrated with- HgbA1C>6.5, or fasting glu>126 mg/dl.

• Any other medical condition that would interfere with testing or increase one's risk of complications during exercise, as judged by the study physicians.

• Any other condition or events considered exclusionary by the PI and/or physician, such as non-compliance.

• Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy procedure).

Related Conditions & MeSH terms

• Aging

Intervention

Behavioral:
• Progressive Resistance Training
Participants will complete 14 weeks (42 sessions, 3x/week) of progressive resistance training which will consist of 8 constant load movements to train all major muscle groups bilaterally.

Drug:
• Metformin
Participants will be randomized to receive metformin in conjunction with their strength training program.

Locations

Country	Name	City	State
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Philip Kern	University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change in Muscle Strength	Determine if metformin treatment augments strength gains in conjunction with progressive resistance training by one repetition maximum assessments. Maximum (1RM) leg extension muscle strength was assessed at week 4 (to account for neurological adaptations during the initial stages of the resistance program) and week 16. The percent change from week 4 to week 16 is reported.	Week 4 and week 16
Other	Percent Change in Total Body Lean Mass by DXA	To determine if metformin improves changes in body composition associated with progressive resistance training. Percent change in total body lean mass in kg was calculated as the difference between week 16 and week 0 from a total body DXA scan.	16 weeks
Other	Insulin Sensitivity	A standard OGTT will be used to determine insulin sensitivity using the Matsuda Index.	16 weeks
Primary	Percent Change in Type 2 Myofiber Cross Sectional Area	The ability of metformin to improve the hypertrophic response to resistance training will be determined. Muscle biopsies of the vastus lateralis will be used to quantify myofiber cross-sectional area. The percent change in type 2 myofiber size between week 16 and week 0 was used.	16 weeks
Secondary	Percent Change in Normal Density Muscle Size by Computed Tomography	The ability of metformin to improve the hypertrophic response at the whole muscle level will be quantified by computed tomography. Percent change in normal density muscle area will be calculated as the difference between week 16 and week 0.	16 weeks