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

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ClinicalTrials.gov Identifier: NCT02308228
Recruitment Status : Completed
First Posted : December 4, 2014
Results First Posted : September 17, 2019
Last Update Posted : September 17, 2019
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 Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 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
Actual Study Start Date : January 14, 2015
Actual Primary Completion Date : December 14, 2017
Actual Study Completion Date : June 28, 2018

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. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

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



Information from the National Library of Medicine

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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
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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
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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
  Study Documents (Full-Text)

Documents provided by Philip Kern, University of Kentucky:
Informed Consent Form  [PDF] February 17, 2014


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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
Results First Posted: September 17, 2019
Last Update Posted: September 17, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Philip Kern, University of Kentucky:
Aging
Hypertrophy
Metformin
Strength
Muscle
Additional relevant MeSH terms:
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Metformin
Hypoglycemic Agents
Physiological Effects of Drugs