EMERALD: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes (EMERALD)
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|ClinicalTrials.gov Identifier: NCT01808690|
Recruitment Status : Completed
First Posted : March 11, 2013
Results First Posted : February 5, 2020
Last Update Posted : April 13, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes||Drug: Metformin Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes|
|Study Start Date :||March 2013|
|Actual Primary Completion Date :||December 2, 2016|
|Actual Study Completion Date :||December 2, 2016|
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.
Placebo Comparator: 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.
- Change in Insulin Sensitivity [ Time Frame: Baseline, Month 3 ]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.
- Change in ADP Time Constant [ Time Frame: Baseline, Month 3 ]
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.
- Change in Pulse Wave Velocity (PWV) [ Time Frame: Baseline, Month 3 ]
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.
- Change in Central Arterial Intimal Medial Thickness (cIMT) [ Time Frame: Baseline, Month 3 ]
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.
- Change in Cardiac Function by Echocardiogram [ Time Frame: Baseline, Month 3 ]Hypothesis 2b: Metformin will improve cardiac function in Type 1 Diabetes by echocardiogram.
- Change in Aortic Wall Sheer Stress (WSS) [ Time Frame: Baseline, Month 3 ]
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.
- Change in Brachial Artery Distensibility [ Time Frame: Baseline, Month 3 ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01808690
|United States, Colorado|
|Children's Hospital Colorado and University of Colorado Denver Health Sciences Center|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Kristen Nadeau, MD, MS||University of Colorado/Children's Hospital Colorado|