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
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Drug: Metformin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 80
Study Start Date: March 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   12 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01808690

Contacts
Contact: Amy West, MS 720-777-5774 amy.west@childrenscolorado.org
Contact: Rose Morehead, MPH 720-777-4354 rose.morehead@childrenscolorado.org

Locations
United States, Colorado
Children's Hospital Colorado and University of Colorado Denver Health Sciences Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Amy West, MS    720-777-5774    amy.west@childrenscolorado.org   
Principal Investigator: Kristen Nadeau, MD MS         
Sponsors and Collaborators
University of Colorado, Denver
American Diabetes Association
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01808690     History of Changes
Other Study ID Numbers: 12-1528, R56DK078645
Study First Received: March 6, 2013
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Adolescent
Youth
Diabetes
Insulin Resistance
Cardiovascular
Metformin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014