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 Overview

• Status: Completed
• Conditions: Obesity; Type 2 Diabetes Mellitus; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: Rosiglitazone; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Rosiglitazone; 2mg to begin then 4mg, twice daily for 4 months; Other Names: 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.	Drug: Placebo; Subject receives placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline in Whole-body Insulin Sensitivity	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).	4 months
Mean Percent Change in Visceral-to-subcutaneous Abdominal Fat	This describes the percent changes of the ratio between visceral and subcutaneous abdominal fat.	4 months
Percentage of Subjects Who Converted Impaired Glucose Tolerance (IGT) to Normal Glucose Tolerance (NGT)	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.	4 months
Mean Percent Change From Baseline in Hepatic Fat Fraction (HFF)	It refers to the percent changes of hepatic fat content.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline in Adiponectin	This refers to the changes of adiponectin levels.	4 months

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Sonia Caprio, MD, Yale School of Medicine Department of Pediatric Endocrinology

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 15, 2006
• First Submitted That Met QC Criteria: December 18, 2006
• First Posted (Estimate): December 19, 2006

Study Record Updates

• Last Update Posted (Estimate): July 22, 2013
• Last Update Submitted That Met QC Criteria: July 15, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Insulin Resistance; Insulin Sensitivity; Type 2 Diabetes Mellitus; Type 2 Diabetes Mellitus (T2DM); Impaired Glucose Tolerance; Impaired Glucose Tolerance (IGT); Childhood and Adolescent Obesity; Metabolic phenotype; Abdominal fat partitioning
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Rosiglitazone
• Other Study ID Numbers: 0508000532