An Early Phase 1 interventional study of Progressive Resistance Training and Metformin in Aging, sponsored by Philip Kern. Completed at 2 sites in United States. Open to participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-09-17.
Sponsored by Philip Kern · Early Phase 1, Interventional, and Supportive care
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.
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.
Philip Kern is the lead sponsor of 9 studies on the registry; 3 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
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.
Also known as: Strength Training
Participants will be randomized to receive metformin in conjunction with their strength training program.
Also known as: Glucophage XR
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.
Time frame: 16 weeks
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.
Time frame: 16 weeks
Percent Change in Muscle Strength
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.
Time frame: Week 4 and week 16
Percent Change in Total Body Lean Mass by DXA
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.
Time frame: 16 weeks
Insulin Sensitivity
A standard OGTT will be used to determine insulin sensitivity using the Matsuda Index.
Time frame: 16 weeks
Number of individuals consented and further screened for eligibility = 144 Number of participants randomized to drug/placebo = 109 Number of participants completing exercise intervention with drug/placebo use = 94
| Milestone | Metformin | Placebo, Sugar Pill |
|---|---|---|
| Started | 54 | 55 |
| Completed | 46 | 48 |
| Not completed | 8 | 7 |
| Withdrew: Adverse event | 3 | 4 |
| Withdrew: Withdrawal by subject | 5 | 3 |
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.
| Percent change | Metformin | Placebo, Sugar Pill |
|---|---|---|
| Percent Change in Type 2 Myofiber Cross Sectional Area | 18.5 ± 31.5 | 14.5 ± 29.7 |
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.
| Percent change | Metformin | Placebo, Sugar Pill |
|---|---|---|
| Percent Change in Normal Density Muscle Size by Computed Tomography | 4.2 ± 9.1 | 10.5 ± 7.0 |
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.
| Percent change | Metformin | Placebo, Sugar Pill |
|---|---|---|
| Percent Change in Muscle Strength | 15.3 ± 18.5 | 23.1 ± 18.9 |
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.
| Percent change | Metformin | Placebo, Sugar Pill |
|---|---|---|
| Percent Change in Total Body Lean Mass by DXA | 0.41 ± 2.25 | 1.95 ± 2.69 |
A standard OGTT will be used to determine insulin sensitivity using the Matsuda Index.
Results for this outcome have not been posted.
Collected over Adverse events are reported from the time the subjects sign the consent form until the completion of the study which includes baseline, medication ramp, exercise intervention, and follow up assessments. The total duration of the study for each subject is approximately 1 year.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin | 0/54 (0%) | 0/54 (0%) | 17/54 (31.5%) |
| Placebo, Sugar Pill | 0/55 (0%) | 0/55 (0%) | 6/55 (10.9%) |
| Event | Metformin | Placebo, Sugar Pill |
|---|---|---|
| Nausea, Diarrhea, FlatulenceGastrointestinal disorders | 17/54 | 1/55 |
| Musculoskeletal Pain or InjuryMusculoskeletal and connective tissue disorders | 4/54 | 5/55 |
| Age, Categorical(Participants) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 2 | 3 |
| >=65 years | 53 | 53 | 106 |
| Age, Continuous(years) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| Mean | 69.4 (66.8 to 72.3) | 69.3 (66.8 to 74.0) | 69.4 (66.8 to 73.2) |
| Sex: Female, Male(Participants) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| Female | 22 | 29 | 51 |
| Male | 24 | 19 | 43 |
| Ethnicity (NIH/OMB)(Participants) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 46 | 48 | 94 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 |
| White | 45 | 47 | 92 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| United States | 54 | 55 | 109 |
| BMI(kg/m^2) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| Mean | 26.9 ± 3.1 | 25.7 ± 3.1 | 26.3 ± 3.1 |
| Short Physical Performance Battery (SPPB)(Scores on a Scale) | Metformin | Placebo, Sugar Pill | Total |
|---|---|---|---|
| Mean | 11 (10 to 12) | 11 (11 to 12) | 11 (10.5 to 12) |
3 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
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Philip Kern