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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sonia Caprio, Yale University
ClinicalTrials.gov Identifier:
NCT00413335
First received: December 15, 2006
Last updated: July 15, 2013
Last verified: July 2013

December 15, 2006
July 15, 2013
November 2005
September 2008   (final data collection date for primary outcome measure)
  • 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.
  • Decrease in the visceral-to-subcutaneous abdominal fat ratio, intrahepatic fat, and intramyocellular lipid content.
  • Improvements in insulin sensitivity and glucose tolerance.
Complete list of historical versions of study NCT00413335 on ClinicalTrials.gov Archive Site
Mean Percent Change From Baseline in Adiponectin [ Time Frame: 4 months ] [ Designated as safety issue: No ]
This refers to the changes of adiponectin levels.
  • Restoration of normal ability of the beta cell to sense and respond to incremental changes in glucose levels.
  • Reduced lipolysis as reflected by a reduced glycerol turnover.
  • Increased adiponectin levels and decreased inflammatory cytokines.
  • Decreased cardiovascular risk factors.
  • Reduction in size but an increase in the number of adipocytes in the subcutaneous fat depot.
  • A change in the expression of genes that are known to be linked to insulin resistance and that are affected by rosiglitazone.
Not Provided
Not Provided
 
Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth
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 (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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Obesity
  • Impaired Glucose Tolerance
  • Type 2 Diabetes Mellitus
  • Drug: Rosiglitazone
    2mg to begin then 4mg, twice daily for 4 months
    Other Name: Avandia
  • Drug: Placebo
    Subject receives placebo.
  • 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.
    Intervention: Drug: Rosiglitazone
  • 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
December 2008
September 2008   (final data collection date for primary outcome measure)

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.
Both
10 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00413335
0508000532
No
Sonia Caprio, Yale University
Yale University
Not Provided
Principal Investigator: Sonia Caprio, MD Yale School of Medicine Department of Pediatric Endocrinology
Yale University
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP