A Phase 3 interventional study of Metformin and Placebo in Type 1 Diabetes, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 12 Years to 21 Years. Per ClinicalTrials.gov, last updated 2021-09-30.
Sponsored by University of Colorado, Denver · Phase 3, Interventional, and Treatment
Diabetes is increasingly common among youth, forecasting early complications. Type 1 (T1D) cause early heart disease, shortening lifespan despite modern improvements in control of blood sugars and other risk factors for heart disease. Poor insulin action, otherwise known as insulin resistance (IR), is the main factor causing heart disease in type 2 diabetes (T2D), but the cause of increased heart disease in T1D is unclear. IR may contribute to heart disease in T1D as in T2D, as the investigators and others have found the presence of IR in T1D. Much less is known about IR in T1D, but a better understanding of its role in T1D is critical to understanding causes of heart disease in T1D. The investigators long-term goal is to understand the early causes of heart disease in diabetes so that we can prevent it. The investigators unique initial findings suggest that even reasonably well-controlled, normal weight, T1D youth are IR. The IR appears directly related to the heart, blood vessel, and exercise defects, but in a pattern that appears very different from T2D. The goals of this study are to determine the unique heart, blood vessel and insulin sensitivity abnormalities in T1D youth, and determine whether metformin improves these abnormalities. A clear understanding of these factors will help determine the causes, and what treatments could help each abnormality.
Hypothesis 1: Metformin will improve insulin function and mitochondrial function in T1D.
Hypothesis 2: Metformin will improve vascular and cardiac function in T1D.
All measures will be performed twice, before and after a 3-month randomized, placebo-controlled design where subjects are randomized to either metformin or placebo. The independent impact of insulin action as well as glucose levels, BMI, T1D duration, and gender on baseline outcomes and the impact of changes in insulin action, glucose levels and BMI on response to metformin will also be examined to help customize future strategies to prevent heart disease in T1D. This study will advance the field by providing new information about the role of poor insulin action in the heart disease of T1D, and whether improving insulin action in T1D is helpful. If a focus on directly improving insulin action in T1D youth is supported by our studies, the clinical approach to T1D management may significantly change.
3,614 studies on the registry are indexed under Diabetes Mellitus, Type 1; 586 are open to participants now.
This study's enrollment of 52 is above the median of 40 across 2,718 interventional studies indexed under Diabetes Mellitus, Type 1.
Browse Diabetes Mellitus, Type 1 studies →University of Colorado, Denver is the lead sponsor of 1,538 studies on the registry; 319 are open to participants now.
Of its 146 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
Drug: Metformin
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.
Drug: Placebo
Change in Insulin Sensitivity
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.
Time frame: Baseline, Month 3
Change in ADP Time Constant
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.
Time frame: Baseline, Month 3
Change in Pulse Wave Velocity (PWV)
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.
Time frame: Baseline, Month 3
Change in Central Arterial Intimal Medial Thickness (cIMT)
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.
Time frame: Baseline, Month 3
Change in Mitral Valve E/A Ratio by Echocardiogram
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.
Time frame: Baseline, Month 3
Change in Aortic Wall Sheer Stress (WSS)
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.
Time frame: Baseline, Month 3
Change in Brachial Artery Distensibility
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.
Time frame: Baseline, Month 3
| Milestone | Metformin | Placebo |
|---|---|---|
| Started | 25 | 23 |
| Completed | 24 | 21 |
| Not completed | 1 | 2 |
| Withdrew: Withdrawal by subject | 1 | 2 |
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.
| (mg/kg/min)/(insulin) | Metformin | Placebo |
|---|---|---|
| Change in Insulin Sensitivity | 12.2 ± 3.2 | -2.4 ± 3.6 |
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.
| seconds (s) | Metformin | Placebo |
|---|---|---|
| Change in ADP Time Constant | 0.46 (-5.62 to 7.72) | -0.47 (-1.55 to 0.34) |
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.
| m/s | Metformin | Placebo |
|---|---|---|
| Change in Pulse Wave Velocity (PWV) | -1.1 ± 1.2 | 4.1 ± 1.6 |
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.
| mm | Metformin | Placebo |
|---|---|---|
| Change in Central Arterial Intimal Medial Thickness (cIMT) | -0.04 ± 0.01 | 0.00 ± 0.10 |
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.
| ratio | Metformin | Placebo |
|---|---|---|
| Change in Mitral Valve E/A Ratio by Echocardiogram | 1.55 ± 0.42 | 1.72 ± 0.34 |
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.
| dyne/cm2 | Metformin | Placebo |
|---|---|---|
| Change in Aortic Wall Sheer Stress (WSS) | -0.3 ± 0.4 | 1.5 ± 0.5 |
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.
| %/mmHg | Metformin | Placebo |
|---|---|---|
| Change in Brachial Artery Distensibility | 0.23 ± 0.19 | 0.16 ± 0.20 |
Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin | 0/25 (0%) | 0/25 (0%) | 10/25 (40%) |
| Placebo | 0/23 (0%) | 0/23 (0%) | 2/23 (8.7%) |
| Event | Metformin | Placebo |
|---|---|---|
| Gastrointestinal Side EffectsGastrointestinal disorders | 10/25 | 2/23 |
| Age, Continuous(years) | Metformin | Placebo | Total |
|---|---|---|---|
| Mean | 17.3 ± 2.3 | 15.9 ± 2.7 | 16.6 ± 2.5 |
| Sex: Female, Male(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| Female | 14 | 10 | 24 |
| Male | 11 | 13 | 24 |
| Ethnicity (NIH/OMB)(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 3 | 4 | 7 |
| Not Hispanic or Latino | 22 | 19 | 41 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 24 | 22 | 46 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
The record gives a start of Mar 2013, a primary completion of Dec 2016 and a completion of Dec 2016. It does not say whether these dates are actual or estimated.
Results were first posted in Feb 2020, 3 years 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Metformin
University of Colorado, Denver →