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

NCT02308228 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: 1R01AG046920-01A1
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 2

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.

Conditions

Aging

Keywords

Aging; Hypertrophy; Metformin; Strength; Muscle

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percent Change in Normal Density Muscle Size by Computed Tomography

  16 weeks

Other Outcomes (3)

• Percent Change in Muscle Strength

  Week 4 and week 16

• Percent Change in Total Body Lean Mass by DXA

  16 weeks

• Insulin Sensitivity

  16 weeks

Study Arms (2)

Metformin

EXPERIMENTAL

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; Drug: Metformin

Placebo, Sugar Pill

PLACEBO COMPARATOR

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

Interventions

Progressive Resistance Training BEHAVIORAL

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.

Also known as: Strength Training

Metformin; Placebo, Sugar Pill

Metformin DRUG

Participants will be randomized to receive metformin in conjunction with their strength training program.

Also known as: Glucophage XR

Metformin

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• ≥65 years of age.
• Independently mobile with a SPPB score 3-12.
• Access to transportation.
• Capable of providing informed consent (cognitively intact).

You may not qualify if:

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

Sponsors & Collaborators

• Philip Kern: lead
• University of Alabama at Birmingham: collaborator

Study Sites (2)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (5)

• Long DE, Kosmac K, Dungan CM, Bamman MM, Peterson CA, Kern PA. Potential Benefits of Combined Statin and Metformin Therapy on Resistance Training Response in Older Individuals. Front Physiol. 2022 Apr 14;13:872745. doi: 10.3389/fphys.2022.872745. eCollection 2022.

  PMID: 35492586 DERIVED

• Long DE, Peck BD, Tuggle SC, Villasante Tezanos AG, Windham ST, Bamman MM, Kern PA, Peterson CA, Walton RG. Associations of muscle lipid content with physical function and resistance training outcomes in older adults: altered responses with metformin. Geroscience. 2021 Apr;43(2):629-644. doi: 10.1007/s11357-020-00315-9. Epub 2021 Jan 18.

  PMID: 33462708 DERIVED

• Walton RG, Dungan CM, Long DE, Tuggle SC, Kosmac K, Peck BD, Bush HM, Villasante Tezanos AG, McGwin G, Windham ST, Ovalle F, Bamman MM, Kern PA, Peterson CA. Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial. Aging Cell. 2019 Dec;18(6):e13039. doi: 10.1111/acel.13039. Epub 2019 Sep 26.

  PMID: 31557380 DERIVED

• Long DE, Villasante Tezanos AG, Wise JN, Kern PA, Bamman MM, Peterson CA, Dennis RA. A guide for using NIH Image J for single slice cross-sectional area and composition analysis of the thigh from computed tomography. PLoS One. 2019 Feb 7;14(2):e0211629. doi: 10.1371/journal.pone.0211629. eCollection 2019.

  PMID: 30730923 DERIVED

• Long DE, Peck BD, Martz JL, Tuggle SC, Bush HM, McGwin G, Kern PA, Bamman MM, Peterson CA. Metformin to Augment Strength Training Effective Response in Seniors (MASTERS): study protocol for a randomized controlled trial. Trials. 2017 Apr 26;18(1):192. doi: 10.1186/s13063-017-1932-5.

  PMID: 28441958 DERIVED

MeSH Terms

Conditions

Hypertrophy

Interventions

Resistance Training; Metformin

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Douglas Long
• Organization: University of Kentucky

DELONG2@UKY.EDU

859-323-5438

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: December 4, 2014
• Study Start: January 14, 2015
• Primary Completion: December 14, 2017
• Study Completion: June 28, 2018
• Last Updated: September 17, 2019
• Results First Posted: September 17, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)