Clinical trial NCT00413335: Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth
Official title: Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Impaired Glucose Tolerance
Type 2 Diabetes Mellitus
Keywords: Childhood and Adolescent Obesity
Metabolic phenotype
Impaired Glucose Tolerance
Type 2 Diabetes Mellitus
Insulin Sensitivity
Insulin Resistance
Abdominal fat partitioning
Impaired Glucose Tolerance (IGT)
Type 2 Diabetes Mellitus (T2DM)
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2006-12-19
Enrollment: 21
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Mean Percent Change From Baseline in Whole-body Insulin Sensitivity
timeFrame: 4 months
measure: Mean Percent Change in Visceral-to-subcutaneous Abdominal Fat
timeFrame: 4 months
measure: Percentage of Subjects Who Converted Impaired Glucose Tolerance (IGT) to Normal Glucose Tolerance (NGT)
timeFrame: 4 months
measure: Mean Percent Change From Baseline in Hepatic Fat Fraction (HFF)
timeFrame: 4 months
Secondary outcomes:
measure: Mean Percent Change From Baseline in Adiponectin
timeFrame: 4 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
Study officials:
affiliation: Yale School of Medicine Department of Pediatric Endocrinology
name: Sonia Caprio, MD
role: PRINCIPAL_INVESTIGATOR
References: