Official Title: “Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth”

The purpose of the study is to determine whether treatment of children and adolescents with Impaired Glucose Tolerance (IGT) with rosiglitazone will lead to improvements in insulin sensitivity and glucose tolerance.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2008

Impaired Glucose Tolerance (IGT) is a prelude to diabetes, which is increasing in prevalence in obese children and adolescents with marked obesity. This condition tends to progress to Type 2 Diabetes Mellitus (T2DM) at an alarmingly rapid tempo. The increased prevalence of childhood and adolescent obesity and greater risk of IGT, and progression to diabetes, in this population set the stage for a series of studies aimed at understanding the metabolic phenotype and natural history of pre-diabetes in obese youth. We found that obese children and adolescents with IGT are characterized by marked insulin resistance related to altered lipid partitioning, favoring lipid deposition in the visceral and intramyocellular compartment. Furthermore, we found an impairment of the acute insulin response in these youngsters. Follow-up revealed a rapid deterioration from IGT to frank diabetes. Based on these studies, there is a strong rationale for changing the balance between visceral and subcutaneous fat and muscle lipid content in a more favorable pattern in order to improve insulin sensitivity.

The primary objective of this study is to determine, in a group of ethnically diverse children and adolescents with IGT, whether treatment with rosiglitazone leads to improvements in insulin sensitivity and glucose tolerance. Secondary objectives are to determine whether rosiglitazone is safe and well tolerated.

Intervention(s) in this Clinical Trial

• Drug: Rosiglitazone
  • 2mg to begin then 4mg, twice daily for 4 months
• Drug: Placebo
  • Subject receives placebo.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Subject receives Rosiglitazone.
• Placebo Comparator: 2
  • Subject receives placebo

Primary Measures

• Improvements in insulin sensitivity and glucose tolerance.
  • Time Frame: 4 months
    Safety Issue?: No
• Decrease in the visceral-to-subcutaneous abdominal fat ratio, intrahepatic fat, and intramyocellular lipid content.
  • Time Frame: 4 months
    Safety Issue?: No

Secondary Measures

• Restoration of normal ability of the beta cell to sense and respond to incremental changes in glucose levels.
  • Time Frame: 4 months
    Safety Issue?: No
• Reduced lipolysis as reflected by a reduced glycerol turnover.
  • Time Frame: 4 months
    Safety Issue?: No
• Increased adiponectin levels and decreased inflammatory cytokines.
  • Time Frame: 4 months
    Safety Issue?: No
• Decreased cardiovascular risk factors.
  • Time Frame: 4 months
    Safety Issue?: No
• Reduction in size but an increase in the number of adipocytes in the subcutaneous fat depot.
  • Time Frame: 4 months
    Safety Issue?: No
• A change in the expression of genes that are known to be linked to insulin resistance and that are affected by rosiglitazone.
  • Time Frame: 4 months
    Safety Issue?: No

Inclusion Criteria:

• Good general health
• Aged 10 to 18 yrs (females: Tanner stage II-V;and males:testes size>6ml)
• IGT based on 2-hr plasma glucose>140mg/dl and <200mg/dl during an OGTT.

Exclusion Criteria:

• Baseline creatinine>1.0mg
• AST and ALT>2.5 ULN
• Anemia (Hct<30)
• Pregnancy (females must have a negative urine pregnancy test during the study)
• Cardiac or pulmonary or other significant chronic illness
• Plans to increase the frequency or intensity of a regular exercise program
• Psychiatric disorder or substance abuse of anorexic agents.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 10 Years

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Yale University

Overall Clinical Trial Officials and Contacts

Sonia Caprio, MD Principal Investigator Yale School of Medicine Department of Pediatric Endocrinology  

Overall Contact: Sonia Caprio, MD 203-785-5692 sonia.caprio@yale.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00413335

Study ID Number: 0508000532

ClinicalTrials.gov Identifier: NCT00413335

Health Authority: United States: Institutional Review Board