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

August 28, 2019 updated by: Philip Kern

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

109

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama Birmingham
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metformin
Participants will be randomized to receive Metformin (1700 mg/day) for a period of 16 weeks; 2 weeks of Metformin only followed by 14 weeks of continued Metformin use in combination with progressive resistance training.
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.
Other Names:
  • Strength Training
Drug: Metformin
Participants will be randomized to receive metformin in conjunction with their strength training program.
Other Names:
  • Glucophage XR
Placebo Comparator: Placebo, Sugar Pill
Participants will be randomized to receive placebo sugar pills (1700 mg/day) for a period of 16 weeks; 2 weeks of placebo only followed by 14 weeks of continued placebo use in combination with progressive resistance training. Placebos will be almost identical to the Metformin medication.
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.
Other Names:
  • Strength Training

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Type 2 Myofiber Cross Sectional Area
Time Frame: 16 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Normal Density Muscle Size by Computed Tomography
Time Frame: 16 weeks
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Muscle Strength
Time Frame: Week 4 and week 16
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
Percent Change in Total Body Lean Mass by DXA
Time Frame: 16 weeks
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
Insulin Sensitivity
Time Frame: 16 weeks
A standard OGTT will be used to determine insulin sensitivity using the Matsuda Index.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Philip Kern

Collaborators

University of Alabama at Birmingham

Investigators

  • Principal Investigator: Philip Kern, M.D., University of Kentucky
  • Principal Investigator: Charlotte Peterson, Ph.D., University of Kentucky
  • Principal Investigator: Marcas Bamman, Ph.D, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 14, 2015

Primary Completion (Actual)

December 14, 2017

Study Completion (Actual)

June 28, 2018

Study Registration Dates

First Submitted

November 25, 2014

First Submitted That Met QC Criteria

December 1, 2014

First Posted (Estimate)

December 4, 2014

Study Record Updates

Last Update Posted (Actual)

September 17, 2019

Last Update Submitted That Met QC Criteria

August 28, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01AG046920-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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