Trial Outcomes & Findings for Exercise Dose and Metformin for Vascular Health in Metabolic Syndrome (NCT NCT03355469)
NCT ID: NCT03355469
Last Updated: 2025-09-22
Results Overview
Endothelial function assessed as a percentage change in brachial artery diameter from baseline to deflation (5 minutes after artery occlusion by blood pressure cuff inflation). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
91 participants
Primary outcome timeframe
0 and 16 weeks
Results posted on
2025-09-22
Participant Flow
Participant milestones
| Measure |
LoEx With Placebo
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
22
|
21
|
24
|
24
|
|
Overall Study
COMPLETED
|
16
|
18
|
20
|
18
|
|
Overall Study
NOT COMPLETED
|
6
|
3
|
4
|
6
|
Reasons for withdrawal
| Measure |
LoEx With Placebo
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Overall Study
COVID-19
|
3
|
2
|
3
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
0
|
3
|
Baseline Characteristics
Exercise Dose and Metformin for Vascular Health in Metabolic Syndrome
Baseline characteristics by cohort
| Measure |
LoEx With Placebo
n=22 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=21 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=24 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=24 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
Total
n=91 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
56.5 years
n=5 Participants
|
54.0 years
n=7 Participants
|
56.0 years
n=5 Participants
|
56.0 years
n=4 Participants
|
56.0 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
71 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
88 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
76 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Body Mass Index
|
31.3 kg/m^2
n=5 Participants
|
33.8 kg/m^2
n=7 Participants
|
35.3 kg/m^2
n=5 Participants
|
36.0 kg/m^2
n=4 Participants
|
34.8 kg/m^2
n=21 Participants
|
|
VO2peak
|
22.6 ml/kg/min
n=5 Participants
|
23.0 ml/kg/min
n=7 Participants
|
22.9 ml/kg/min
n=5 Participants
|
21.1 ml/kg/min
n=4 Participants
|
22.5 ml/kg/min
n=21 Participants
|
PRIMARY outcome
Timeframe: 0 and 16 weeksPopulation: Analysis includes only individuals that had both pre and post data.
Endothelial function assessed as a percentage change in brachial artery diameter from baseline to deflation (5 minutes after artery occlusion by blood pressure cuff inflation). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Outcome measures
| Measure |
LoEx With Placebo
n=12 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=11 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=16 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=9 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery
|
-0.45 Percent change in diameters
Interval -3.47 to 2.56
|
0.76 Percent change in diameters
Interval -4.17 to 5.7
|
3.50 Percent change in diameters
Interval 0.65 to 6.46
|
5.28 Percent change in diameters
Interval 0.67 to 9.88
|
SECONDARY outcome
Timeframe: 0 and 16 weeksPopulation: Analysis includes only individuals that had both pre and post data.
The glucose infusion rate (mg/kg/min) divided by steady-state insulin (uU/mL) during a 120 minute euglycemic-hyperinsulinemic clamp provides an index of metabolic insulin sensitivity. Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Outcome measures
| Measure |
LoEx With Placebo
n=14 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=16 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=19 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=14 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Change in Metabolic Insulin Sensitivity. Glucose Infusion Rate Normalized to Steady-State Insulin (GIR).
|
0.0012 (mg/kg/min)/(uU/mL)
Interval -0.0131 to 0.0155
|
0.011 (mg/kg/min)/(uU/mL)
Interval 0.0047 to 0.0173
|
0.0086 (mg/kg/min)/(uU/mL)
Interval -0.0011 to 0.0182
|
0.0053 (mg/kg/min)/(uU/mL)
Interval -0.0051 to 0.0158
|
SECONDARY outcome
Timeframe: 0 and 16 weeksPopulation: Analysis includes only individuals that had both pre and post data.
Measure of Arterial Stiffness calculated by dividing the augmentation pressure by the pulse pressure, then multiplying by 100 and normalizing to a heart rate of 75 bpm (AIx75). Delta = Week 16 - Week 0. Lower values and negative change scores following the intervention indicate a better outcome.
Outcome measures
| Measure |
LoEx With Placebo
n=15 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=17 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=20 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=15 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Change in Fasting Augmentation Index
|
-1.33 Percent of pulse pressure
Interval -7.84 to 5.17
|
-4.65 Percent of pulse pressure
Interval -9.35 to 0.06
|
0.00 Percent of pulse pressure
Interval -4.81 to 4.81
|
-1.20 Percent of pulse pressure
Interval -4.5 to 2.1
|
SECONDARY outcome
Timeframe: 0 and 16 weeksPopulation: Analysis includes only individuals that had both pre and post data.
Product of microvascular blood volume (VI; video intensity units) and microvascular flow velocity (sec\^-1). Insulin-stimulated microvascular blood flow is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Outcome measures
| Measure |
LoEx With Placebo
n=10 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=7 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=15 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=7 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Change in Insulin-stimulated Microvascular Blood Flow (MBF) of the Forearm.
|
0.027 VI * sec^-1
Interval -0.003 to 0.056
|
0.041 VI * sec^-1
Interval -0.037 to 0.119
|
-0.026 VI * sec^-1
Interval -0.059 to 0.007
|
-0.065 VI * sec^-1
Interval -0.128 to -0.001
|
SECONDARY outcome
Timeframe: 0 and 16 weeksPopulation: Analysis includes only individuals that had both pre and post data.
Replenishment curves of the forearm flexor muscle acquired during steady-state infusion of Definity microbubbles. Insulin-stimulated microvascular flow velocity is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Outcome measures
| Measure |
LoEx With Placebo
n=10 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=7 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=15 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=7 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Change in Insulin-stimulated Microvascular Flow Velocity (MFV) of the Forearm.
|
0.006 sec^-1
Interval -0.004 to 0.015
|
0.009 sec^-1
Interval -0.013 to 0.032
|
-0.007 sec^-1
Interval -0.017 to 0.003
|
-0.018 sec^-1
Interval -0.035 to -0.001
|
SECONDARY outcome
Timeframe: 0 and 16 weeksPopulation: Analysis includes only individuals that had both pre and post data.
Replenishment curves of the forearm flexor muscle acquired during steady-state infusion of Definity microbubbles. Insulin-stimulated microvascular blood volume is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Outcome measures
| Measure |
LoEx With Placebo
n=10 Participants
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=7 Participants
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=15 Participants
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=7 Participants
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Change in Insulin-stimulated Microvascular Blood Volume (MBV) of the Forearm.
|
0.188 Video Intensity Units (VI)
Interval -0.015 to 0.392
|
0.433 Video Intensity Units (VI)
Interval -0.229 to 1.096
|
-0.257 Video Intensity Units (VI)
Interval -0.52 to 0.006
|
-0.510 Video Intensity Units (VI)
Interval -1.046 to 0.026
|
Adverse Events
LoEx With Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HiEx With Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
LoEx With Metformin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HiEx With Metformin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LoEx With Placebo
n=22 participants at risk
Low intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Placebo
n=21 participants at risk
High intensity exercise with placebo.
Placebo: Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
LoEx With Metformin
n=24 participants at risk
Low intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
Low Intensity Exercise: Low intensity exercise will consist of 16 weeks of walking at \~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
HiEx With Metformin
n=24 participants at risk
High intensity exercise with metformin.
Metformin: Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
High Intensity Exercise: High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal Distress
|
0.00%
0/22 • Adverse events were collected after the first dose of double-blind study medication and within 14 days after the last dose of double-blind study medication, an average of 18 weeks.
Any event reported by the participant or observed by the study staff was was documented and reported to the Institutional Review Board, irrespective of the relation to the research study. Adverse events were collected in a non-systematic method by which participants reported events or in response to to open-ended questions, which occurred once every week for 16 weeks.
|
0.00%
0/21 • Adverse events were collected after the first dose of double-blind study medication and within 14 days after the last dose of double-blind study medication, an average of 18 weeks.
Any event reported by the participant or observed by the study staff was was documented and reported to the Institutional Review Board, irrespective of the relation to the research study. Adverse events were collected in a non-systematic method by which participants reported events or in response to to open-ended questions, which occurred once every week for 16 weeks.
|
0.00%
0/24 • Adverse events were collected after the first dose of double-blind study medication and within 14 days after the last dose of double-blind study medication, an average of 18 weeks.
Any event reported by the participant or observed by the study staff was was documented and reported to the Institutional Review Board, irrespective of the relation to the research study. Adverse events were collected in a non-systematic method by which participants reported events or in response to to open-ended questions, which occurred once every week for 16 weeks.
|
4.2%
1/24 • Adverse events were collected after the first dose of double-blind study medication and within 14 days after the last dose of double-blind study medication, an average of 18 weeks.
Any event reported by the participant or observed by the study staff was was documented and reported to the Institutional Review Board, irrespective of the relation to the research study. Adverse events were collected in a non-systematic method by which participants reported events or in response to to open-ended questions, which occurred once every week for 16 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place