Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth

NCT ID: NCT00413335

Last Updated: 2013-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2008-12-31

Brief Summary

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.

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.

Conditions

Obesity; Impaired Glucose Tolerance; Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Rosiglitazone

Intervention Type: DRUG

2mg to begin then 4mg, twice daily for 4 months

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subject receives placebo.

Interventions

Rosiglitazone

2mg to begin then 4mg, twice daily for 4 months

Intervention Type: DRUG

Placebo

Subject receives placebo.

Intervention Type: DRUG

Other Intervention Names

Avandia

Eligibility Criteria

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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Sonia Caprio

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sonia Caprio, MD

Role: PRINCIPAL_INVESTIGATOR

Yale School of Medicine Department of Pediatric Endocrinology

Locations

Yale School of Medicine

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

0508000532

Identifier Type: -

Identifier Source: org_study_id