Trial Outcomes & Findings for EMERALD: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes (NCT NCT01808690)
NCT ID: NCT01808690
Last Updated: 2021-09-30
Results Overview
Hypothesis 1: Metformin will improve insulin function in Type 1 Diabetes. Insulin function will be measured using a euglycemic-hyperinsulinemic clamp procedure at both baseline and after 3 months of treatment. A clamp measures insulin sensitivity. A higher number indicates a better outcome; a lower number indicates a worse outcome.
COMPLETED
PHASE3
52 participants
Baseline, Month 3
2021-09-30
Participant Flow
Three (3) enrolled participants decided against participation in the study before randomization occurred.
Participant milestones
| Measure |
Metformin
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
23
|
|
Overall Study
COMPLETED
|
24
|
21
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Metformin
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
EMERALD: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
Metformin
n=25 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=23 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
17.3 years
STANDARD_DEVIATION 2.3 • n=5 Participants
|
15.9 years
STANDARD_DEVIATION 2.7 • n=7 Participants
|
16.6 years
STANDARD_DEVIATION 2.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Month 3Population: Metformin group: 1 participant lost to follow-up, 1 IV access problem Placebo group: 2 lost to follow-up, 2 IV access problems
Hypothesis 1: Metformin will improve insulin function in Type 1 Diabetes. Insulin function will be measured using a euglycemic-hyperinsulinemic clamp procedure at both baseline and after 3 months of treatment. A clamp measures insulin sensitivity. A higher number indicates a better outcome; a lower number indicates a worse outcome.
Outcome measures
| Measure |
Metformin
n=23 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=19 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in Insulin Sensitivity
|
12.2 (mg/kg/min)/(insulin)
Standard Deviation 3.2
|
-2.4 (mg/kg/min)/(insulin)
Standard Deviation 3.6
|
SECONDARY outcome
Timeframe: Baseline, Month 3Population: 22 participants had both pre/post MRS data
Hypothesis 1b: Metformin will improve mitochondrial function in Type 1 Diabetes. 31Phosphorus magnetic resonance spectroscopy (MRS) was used before, during, and after 90 seconds of near-maximal isometric exercise of the calf muscle for post-exercise muscle mitochondrial function. ADP time constant is the time for conversion of ADP → ATP and is a measure of muscle mitochondrial health (energy metabolism). A faster recovery is a better outcome; a slower recovery is a worse outcome.
Outcome measures
| Measure |
Metformin
n=12 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=10 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in ADP Time Constant
|
0.46 seconds (s)
Interval -5.62 to 7.72
|
-0.47 seconds (s)
Interval -1.55 to 0.34
|
SECONDARY outcome
Timeframe: Baseline, Month 3Population: Number of participants analyzed differs from participant flow numbers because the institution's MRI scanner was unavailable during replacement.
Hypothesis 2a: Metformin will improve central vascular function in Type 1 Diabetes via pulse wave velocity (PWV) by MRI. PWV is a measure of central arterial stiffness. A lower value indicates a better outcome.
Outcome measures
| Measure |
Metformin
n=20 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=17 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in Pulse Wave Velocity (PWV)
|
-1.1 m/s
Standard Deviation 1.2
|
4.1 m/s
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Baseline, Month 3Population: Metformin: 1 lost to follow-up Placebo: 2 lost to follow-up
Hypothesis 2a: Metformin will improve central vascular function in Type 1 Diabetes via central arterial intimal medial (cIMT) thickness by carotid ultrasound. cIMT is a measure used to diagnose the extent of carotid atherosclerotic vascular disease. The test measures the thickness of the inner two layers of the carotid artery-the intima and media. A lower result is a better outcome.
Outcome measures
| Measure |
Metformin
n=24 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=21 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in Central Arterial Intimal Medial Thickness (cIMT)
|
-0.04 mm
Standard Deviation 0.01
|
0.00 mm
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: Baseline, Month 3Population: Metformin: 2 lost to follow-up Placebo: 2 lost to follow-up, 1 echocardiogram not performed
Hypothesis 2b: Metformin will improve cardiac function in Type 1 Diabetes by echocardiogram. Mitral Valve E/A ratio is the ratio of early (E) to late (A) ventricular filling velocities. Ideal myocardial tissue relaxation is indicated by a ratio of \>0.8 and \<2.0.
Outcome measures
| Measure |
Metformin
n=23 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=20 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in Mitral Valve E/A Ratio by Echocardiogram
|
1.55 ratio
Standard Deviation 0.42
|
1.72 ratio
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: Baseline, Month 3Population: Number of participants analyzed differs from participant flow numbers because the institution's MRI scanner was unavailable during replacement.
Hypothesis 2a: Metformin will improve central vascular function in Type 1 Diabetes via Aortic Wall Sheer Stress (WSS) by MRI. WSS is a measure of central arterial stiffness. A lower value indicates a better outcome.
Outcome measures
| Measure |
Metformin
n=20 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=17 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in Aortic Wall Sheer Stress (WSS)
|
-0.3 dyne/cm2
Standard Deviation 0.4
|
1.5 dyne/cm2
Standard Deviation 0.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Month 3Population: Metformin: 1 lost to follow-up Placebo: 2 lost to follow-up
Hypothesis 2a: Metformin will improve peripheral arterial stiffness in Type 1 Diabetes via Dynapulse. Peripheral arterial stiffness is measured by the distensibility of the arterial wall. Increased arterial stiffness results from reduced elasticity of the arterial wall. A higher result is a better outcome.
Outcome measures
| Measure |
Metformin
n=24 Participants
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=21 Participants
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Change in Brachial Artery Distensibility
|
0.23 %/mmHg
Standard Deviation 0.19
|
0.16 %/mmHg
Standard Deviation 0.20
|
Adverse Events
Metformin
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin
n=25 participants at risk
Metformin will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to placebo.
Metformin
|
Placebo
n=23 participants at risk
Placebo will be given at a dose of 1000 mg twice a day orally for three months to assess changes in insulin resistance compared to metformin.
Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal Side Effects
|
40.0%
10/25 • 3 months
|
8.7%
2/23 • 3 months
|
Additional Information
Dr. Kristen J Nadeau
University of Colorado Denver/Children's Hospital Colorado
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place