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
  Purpose

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.


Condition Intervention
Obesity
Impaired Glucose Tolerance
Type 2 Diabetes Mellitus
Drug: Rosiglitazone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Mean Percent Change From Baseline in Adiponectin [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    This refers to the changes of adiponectin levels.


Enrollment: 21
Study Start Date: November 2005
Study Completion Date: December 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413335

Locations
United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Sonia Caprio, MD Yale School of Medicine Department of Pediatric Endocrinology
  More Information

No publications provided

Responsible Party: Sonia Caprio, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00413335     History of Changes
Other Study ID Numbers: 0508000532
Study First Received: December 15, 2006
Results First Received: November 7, 2012
Last Updated: July 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
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)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014