AgingEarly Phase 1NCT02308228
Metformin to Augment Strength Training Effective Response in Seniors (MASTERS)
A Early Phase 1 study testing Progressive Resistance Training and Metformin in people with Aging, run by Philip Kern at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Progressive Resistance Training and Metformin
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 109 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Jan 2015to 28 Jun 2018
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- ≥65 years of age.
- Independently mobile with a SPPB score 3-12.
- Access to transportation.
- Capable of providing informed consent (cognitively intact).
Who cannot join
- 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.
Show all 15Show fewer
- 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama Birmingham
Birmingham, Alabama, 35294
University of Kentucky
Lexington, Kentucky, 40536
About this study
Official title: 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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Progressive Resistance TrainingBehavioural
Also called Strength 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.
MetforminDrug
Also called Glucophage XR
Participants will be randomized to receive metformin in conjunction with their strength training program.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Progressive Resistance Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks
Secondary outcomes (1)
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.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study start14 Jan 2015
- Primary completion14 Dec 2017
- Study completion28 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philip Kern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alabama at Birmingham
- Responsible party
- Sponsor-investigator, Philip Kern, University of Kentucky
- Investigators
- Charlotte Peterson, Ph.D., Principal investigator, University of KentuckyPhilip Kern, M.D., Principal investigator, University of KentuckyMarcas Bamman, Ph.D, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02308228
- Sponsor's protocol ID
- 1R01AG046920-01A1
- Status last verified
- Aug 2019
- First submitted
- 25 Nov 2014
- Last updated
- 17 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35492586Long 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.
PubMed 33462708Walton 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.
PubMed 31557380Long 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.
PubMed 30730923Long 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.
PubMed 28441958
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Actions of Metformin to Augment Resistance Training Adaptations in Older Adults
- ClinicalTrials.gov ID
- NCT02308228
- Acronym / sponsor ID
- 1R01AG046920-01A1
- Conditions
- Aging
- Keywords
- Aging, Hypertrophy, Metformin, Strength, Muscle
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- Philip KernUniversity, hospital or other
- Collaborators
- University of Alabama at Birmingham
- Study start
- 14 Jan 2015 (actual)
- Primary completion
- 14 Dec 2017 (actual)
- Study completion
- 28 Jun 2018 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Posted 17 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Behavioral: Progressive Resistance Training, Drug: MetforminParticipants 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. |
| Placebo, Sugar Pill | Placebo comparator | Behavioral: Progressive Resistance TrainingParticipants 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- ≥65 years of age.
- Independently mobile with a SPPB score 3-12.
- Access to transportation.
- Capable of providing informed consent (cognitively intact).
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Progressive Resistance TrainingAlso: Strength TrainingParticipants 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. | Behavioural | Metformin, Placebo, Sugar Pill |
| MetforminAlso: Glucophage XRParticipants will be randomized to receive metformin in conjunction with their strength training program. | Drug | Metformin |
Primary outcome
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.
1 secondary outcome
Percent Change in Normal Density Muscle Size by Computed Tomography
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35492586Long 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.
- Derived from this study: PubMed 33462708Long 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.
- Derived from this study: PubMed 31557380Walton 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.
- Derived from this study: PubMed 30730923Long 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.
- Derived from this study: PubMed 28441958Long 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.
- Individual participant dataSharing planned: No
Related trials for Aging
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
RecruitingPhase 2
Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
Not yet recruitingPhase 2
Validation & Intervention Testing for Aging, Longevity and Healthspan
Aging, Functional Decline
RecruitingObservational study
Effects of Obesity on Physical Abilities and Daily Living Activities in Elderly Adults
Obesity, Sarcopenic Obesity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charlotte Peterson, Ph.D. principal investigator
University of Kentucky
Philip Kern, M.D. principal investigator
University of Kentucky
Marcas Bamman, Ph.D principal investigator
University of Alabama at Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Progressive Resistance Training and Metformin in people with Aging, run by Philip Kern at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Type 2 Myofiber Cross Sectional Area (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02308228, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.