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

Yale University

Status: Completed

Conditions: Impaired Glucose Tolerance; Type 2 Diabetes Mellitus; Obesity

Treatments: Drug: Placebo; Drug: Rosiglitazone

Study type: Interventional

Funder types: Other

Identifiers

NCT00413335

0508000532

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 10 to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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21 participants in 2 patient groups, including a placebo group

1

Active Comparator group

Description:

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.

Treatment:

Drug: Rosiglitazone

2

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo