Trial Outcomes & Findings for Metformin to Augment Strength Training Effective Response in Seniors (MASTERS) (NCT NCT02308228)

Last Updated: 2019-09-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

109 participants

Primary outcome timeframe

16 weeks

Results posted on

2019-09-17

Participant Flow

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

Participants may have been excluded prior to randomization to study drug for the following reasons: 1. Screen fail (OGTT, ECG, Blood results) 2. Withdrawals (changed mind, lost to follow up, spouse screen fail)

Participant milestones

Participant milestones
Measure	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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	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. 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.
Overall Study STARTED	54	55
Overall Study COMPLETED	46	48
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	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. 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.
Overall Study Adverse Event	3	4
Overall Study Withdrawal by Subject	5	3

Baseline Characteristics

Data analyzed for those who completed the interventions = 94

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 16 weeks

Population: The largest, highest quality pairs of baseline and week 16 mounts were used for quantification of immunohistochemistry (N=30/group)

Outcome measures

Outcome measures
Measure	Metformin n=30 Participants 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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	Placebo, Sugar Pill n=30 Participants 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. 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.
Percent Change in Type 2 Myofiber Cross Sectional Area	18.5 Percent change Standard Deviation 31.5	14.5 Percent change Standard Deviation 29.7

SECONDARY outcome

Timeframe: 16 weeks

Population: Missing data points include those who, based on femur area, CT positioning at post measure was incorrect = 16. In addition, 1 subject was excluded from analysis as CT data indicated 45% loss of thigh muscle area, which was not consistent with other data for this subject.

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.

Outcome measures

Outcome measures
Measure	Metformin n=37 Participants 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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	Placebo, Sugar Pill n=40 Participants 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. 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.
Percent Change in Normal Density Muscle Size by Computed Tomography	4.2 Percent change Standard Deviation 9.1	10.5 Percent change Standard Deviation 7.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4 and week 16

Population: Some participants were not able to complete the procedure on the day of testing, injured etc

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.

Outcome measures

Outcome measures
Measure	Metformin n=44 Participants 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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	Placebo, Sugar Pill n=45 Participants 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. 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.
Percent Change in Muscle Strength	15.3 Percent change Standard Deviation 18.5	23.1 Percent change Standard Deviation 18.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Population: Analysis of lean muscle mass for those who completed the interventions.

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.

Outcome measures

Outcome measures
Measure	Metformin n=46 Participants 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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	Placebo, Sugar Pill n=48 Participants 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. 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.
Percent Change in Total Body Lean Mass by DXA	0.41 Percent change Standard Deviation 2.25	1.95 Percent change Standard Deviation 2.69

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

A standard OGTT will be used to determine insulin sensitivity using the Matsuda Index.

Outcome measures

Outcome data not reported

Adverse Events

Metformin

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo, Sugar Pill

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Metformin n=54 participants at risk 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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	Placebo, Sugar Pill n=55 participants at risk 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. 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.
Gastrointestinal disorders Nausea, Diarrhea, Flatulence	31.5% 17/54 • Number of events 18 • 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. AEs are reported in real time by close research coordinator and participant interaction. They are graded according to intensity and causality and reported to the IRB in the appropriate amount of time. AEs were grouped according to body system such as musculoskeletal or gastrointestinal and reported together.	1.8% 1/55 • Number of events 1 • 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. AEs are reported in real time by close research coordinator and participant interaction. They are graded according to intensity and causality and reported to the IRB in the appropriate amount of time. AEs were grouped according to body system such as musculoskeletal or gastrointestinal and reported together.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain or Injury	7.4% 4/54 • Number of events 4 • 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. AEs are reported in real time by close research coordinator and participant interaction. They are graded according to intensity and causality and reported to the IRB in the appropriate amount of time. AEs were grouped according to body system such as musculoskeletal or gastrointestinal and reported together.	9.1% 5/55 • Number of events 5 • 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. AEs are reported in real time by close research coordinator and participant interaction. They are graded according to intensity and causality and reported to the IRB in the appropriate amount of time. AEs were grouped according to body system such as musculoskeletal or gastrointestinal and reported together.

Additional Information

Douglas Long

University of Kentucky

Phone: 859-323-5438

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Metformin n=54 Participants 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. 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. Metformin: Participants will be randomized to receive metformin in conjunction with their strength training program.	Placebo, Sugar Pill n=55 Participants 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. 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.	Total n=109 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=54 Participants	0 Participants n=55 Participants	0 Participants n=109 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=54 Participants	2 Participants n=55 Participants	3 Participants n=109 Participants
Age, Categorical >=65 years	53 Participants n=54 Participants	53 Participants n=55 Participants	106 Participants n=109 Participants
Age, Continuous	69.4 years n=46 Participants • Data analyzed for those who completed the interventions = 94	69.3 years n=48 Participants • Data analyzed for those who completed the interventions = 94	69.4 years n=94 Participants • Data analyzed for those who completed the interventions = 94
Sex: Female, Male Female	22 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	29 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	51 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Sex: Female, Male Male	24 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	19 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	43 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	48 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	94 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) Asian	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	1 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	1 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) Black or African American	1 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	1 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) White	45 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	47 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	92 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) More than one race	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=46 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=48 Participants • Data analyzed for those who completed the interventions = 94	0 Participants n=94 Participants • Data analyzed for those who completed the interventions = 94
Region of Enrollment United States	54 participants n=54 Participants	55 participants n=55 Participants	109 participants n=109 Participants
BMI	26.9 kg/m^2 STANDARD_DEVIATION 3.1 • n=46 Participants • Data analyzed for those who completed the interventions = 94	25.7 kg/m^2 STANDARD_DEVIATION 3.1 • n=48 Participants • Data analyzed for those who completed the interventions = 94	26.3 kg/m^2 STANDARD_DEVIATION 3.1 • n=94 Participants • Data analyzed for those who completed the interventions = 94
Short Physical Performance Battery (SPPB)	11 Scores on a Scale n=46 Participants • Data analyzed for those who completed the interventions = 94	11 Scores on a Scale n=48 Participants • Data analyzed for those who completed the interventions = 94	11 Scores on a Scale n=94 Participants • Data analyzed for those who completed the interventions = 94
Physical Activity Survey for the Elderly (PASE)	155.5 Scores on a Scale n=46 Participants • Data analyzed for those who completed the interventions = 94	165.7 Scores on a Scale n=48 Participants • Data analyzed for those who completed the interventions = 94	159.3 Scores on a Scale n=94 Participants • Data analyzed for those who completed the interventions = 94
Short Form-36 Physical Component (SF-36)	54.7 Scores on a Scale n=46 Participants • Data analyzed for those who completed the interventions = 94	55.2 Scores on a Scale n=48 Participants • Data analyzed for those who completed the interventions = 94	55.0 Scores on a Scale n=94 Participants • Data analyzed for those who completed the interventions = 94
Short Form-36 Mental Component (SF-36)	56.7 Scores on a Scale n=46 Participants • Data analyzed for those who completed the interventions = 94	56.5 Scores on a Scale n=48 Participants • Data analyzed for those who completed the interventions = 94	56.6 Scores on a Scale n=94 Participants • Data analyzed for those who completed the interventions = 94