EMERALD: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Colorado, Denver
Sponsor:
Collaborators:
American Diabetes Association
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01808690
First received: March 6, 2013
Last updated: December 17, 2013
Last verified: December 2013

March 6, 2013
December 17, 2013
March 2013
December 2017   (final data collection date for primary outcome measure)
  • Insulin Function [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Hypothesis 1: Metformin will improve insulin function and mitochondrial 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.
  • Cardiovascular Function [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Hypothesis 2: Metformin will improve vascular and cardiac function in Type 1 Diabetes. Cardiac and vascular function will be measured using echocardiogram and vascular reactivity using inflatable cuffs.
  • Insulin Function [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Hypothesis 1: Metformin will improve insulin function and mitochondrial 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.
  • Cardiovascular Function [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Hypothesis 2: Metformin will improve vascular and cardiac function in Type 1 Diabetes. Cardiac and vascular function will be measured using echocardiogram and vascular reactivity using inflatable cuffs.
Complete list of historical versions of study NCT01808690 on ClinicalTrials.gov Archive Site
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EMERALD: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes
Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes

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 we 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. Our long-term goal is to understand the early causes of heart disease in diabetes so that we can prevent it. Our 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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Type 1 Diabetes
  • Drug: Metformin
  • Drug: Placebo
  • Placebo Comparator: 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.
    Intervention: Drug: Metformin
  • 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
March 2018
December 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Adolescents 12-19 years of age with type 1 diabetes (defined as having positive antibodies as well as insulin requirement)
  2. Sedentary nature (<3 hours of physical activity/week)
  3. Willing to consent for participation in study
  4. Body Mass Index (BMI) >5% on growth charts

Exclusion Criteria:

  1. Current use of medications known to affect insulin sensitivity: oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, metformin or thiazolidinediones.
  2. Currently pregnant or breastfeeding women
  3. Use of a thiazolidinedione within 12 weeks
  4. Severe illness or Diabetic Ketoacidosis within 60 days
  5. Macroalbuminuria
  6. Hemoglobin A1c > 12%
  7. Weight > 136.4 kg or < 42 kg, BMI < 5%
  8. Creatinine > 1.2
  9. Hemoglobin < 9
  10. Major psychiatric or developmental disorder limiting informed consent
  11. Implanted metal devices
  12. Inability to tolerate ≥500mg twice a day of metformin
Both
12 Years to 19 Years
No
Contact: Amy West, MS 720-777-5774 amy.west@childrenscolorado.org
Contact: Rose Morehead, MPH 720-777-4354 rose.morehead@childrenscolorado.org
United States
 
NCT01808690
12-1528, R56DK078645
Yes
University of Colorado, Denver
University of Colorado, Denver
  • American Diabetes Association
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
University of Colorado, Denver
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP