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.
Impaired Glucose Tolerance
Type 2 Diabetes Mellitus
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth|
- Mean Percent Change From Baseline in Whole-body Insulin Sensitivity [ Time Frame: 4 months ] [ Designated as safety issue: No ]This describes the percent changes in insulin sensitivity. Insulin sensitivity was expressed as whole body insulin sensitivity index (WBISI) which is based on the values of insulin (microunits per milliliter) and glucose (milligrams per deciliter) obtained from the OGTT and the corresponding fasting values.The formula is: WBISI=10.000/square root of (fasting glucose x fasting insulin)x(mean glucose x mean insulin).
- Mean Percent Change in Visceral-to-subcutaneous Abdominal Fat [ Time Frame: 4 months ] [ Designated as safety issue: No ]This describes the percent changes of the ratio between visceral and subcutaneous abdominal fat.
- Percentage of Subjects Who Converted Impaired Glucose Tolerance (IGT) to Normal Glucose Tolerance (NGT) [ Time Frame: 4 months ] [ Designated as safety issue: No ]This refers to the number of subjects that converted from IGT to NGT. NGT is defined as fasting glucose lower than 100 mg/dl and 2 hours glucose lower than 140 mg/dl. IGT is defined as 2 hours glucose higher than 140 mg/dl.
- Mean Percent Change From Baseline in Hepatic Fat Fraction (HFF) [ Time Frame: 4 months ] [ Designated as safety issue: No ]It refers to the percent changes of hepatic fat content.
- Mean Percent Change From Baseline in Adiponectin [ Time Frame: 4 months ] [ Designated as safety issue: No ]This refers to the changes of adiponectin levels.
|Study Start Date:||November 2005|
|Study Completion Date:||December 2008|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Subject undergoes ogtt, hyperinsulinemic-euglycemic clamp, abdominal and liver MRI, NMR and DEXA scan. Subject then receives Rosiglitazone. Subjects are followed every 2 weeks. Imaging repeated at 2 months. 12 week follow up. And then all tests are repeated at 4 months.
2mg to begin then 4mg, twice daily for 4 months
Other Name: Avandia
Placebo Comparator: 2
Subject has ogtt, hyperinsulinemic-euglycemic clamp, abdominal and liver MRI, DEXA, NMR. Subject is randomized (double-blind) to placebo. Is followed every 2 weeks, repeats imaging at 2 months, is seen at 12 weeks and then repeats all tests at 2 months.
Subject receives placebo.
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. The investigators 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, the investigators 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413335
|United States, Connecticut|
|Yale School of Medicine|
|New Haven, Connecticut, United States, 06520|
|Principal Investigator:||Sonia Caprio, MD||Yale School of Medicine Department of Pediatric Endocrinology|