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

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ClinicalTrials.gov Identifier: NCT02308228
Recruitment Status : Active, not recruiting
First Posted : December 4, 2014
Last Update Posted : June 27, 2018
Sponsor:
Collaborator:
University of Alabama at Birmingham
Information provided by (Responsible Party):
Philip Kern, University of Kentucky

Brief 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.

Condition or disease Intervention/treatment Phase
Aging Behavioral: Progressive Resistance Training Drug: Metformin Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Novel Actions of Metformin to Augment Resistance Training Adaptations in Older Adults
Study Start Date : September 2014
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


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 Name: Strength Training

Drug: Metformin
Participants will be randomized to receive metformin in conjunction with their strength training program.
Other Name: 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 Name: Strength Training




Primary Outcome Measures :
  1. Myofiber Size (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.


Secondary Outcome Measures :
  1. Muscle Size by CT (normal and low density) [ Time Frame: 16 weeks ]
    The ability of metformin to improve the hypertrophic response at the whole muscle level will be quantified by computed tomography including normal and low density thigh muscle cross-sectional areas.


Other Outcome Measures:
  1. Muscle Strength [ Time Frame: 14 weeks ]
    Determine if metformin treatment augments strength gains in conjunction with progressive resistance training by one repetition maximum assessments.

  2. Body composition by DXA [ Time Frame: 16 weeks ]
    To determine if metformin improves changes in body composition associated with progressive resistance training.

  3. Insulin Sensitivity [ Time Frame: 16 weeks ]
    A standard OGTT will be used to determine insulin sensitivity using the Matsuda Index.



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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02308228


Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Philip Kern
University of Alabama at Birmingham
Investigators
Principal Investigator: Charlotte Peterson, Ph.D. University of Kentucky
Principal Investigator: Philip Kern, M.D. University of Kentucky
Principal Investigator: Marcas Bamman, Ph.D University of Alabama at Birmingham

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Philip Kern, M.D., University of Kentucky
ClinicalTrials.gov Identifier: NCT02308228     History of Changes
Other Study ID Numbers: 1R01AG046920-01A1 ( U.S. NIH Grant/Contract )
First Posted: December 4, 2014    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

Keywords provided by Philip Kern, University of Kentucky:
Aging
Hypertrophy
Metformin
Strength
Muscle

Additional relevant MeSH terms:
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs