Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth - Full Text View

Sponsor:	Yale University
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00413335

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:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Obesity Obesity in Children

Drug Information available for: Dextrose Rosiglitazone Rosiglitazone Maleate

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

Improvements in insulin sensitivity and glucose tolerance. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Decrease in the visceral-to-subcutaneous abdominal fat ratio, intrahepatic fat, and intramyocellular lipid content. [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Restoration of normal ability of the beta cell to sense and respond to incremental changes in glucose levels. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Reduced lipolysis as reflected by a reduced glycerol turnover. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Increased adiponectin levels and decreased inflammatory cytokines. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Decreased cardiovascular risk factors. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Reduction in size but an increase in the number of adipocytes in the subcutaneous fat depot. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
A change in the expression of genes that are known to be linked to insulin resistance and that are affected by rosiglitazone. [ Time Frame: 4 months ] [ Designated as safety issue: No ]

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
1: Active Comparator 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
2: Placebo Comparator 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. We 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, we 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

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:	Yale University ( Sonia Caprio, MD/Professor of Pediatrics )
Study ID Numbers:	0508000532
Study First Received:	December 15, 2006
Last Updated:	January 13, 2010
ClinicalTrials.gov Identifier:	NCT00413335 History of Changes
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
Childhood and Adolescent Obesity
Impaired Glucose Tolerance (IGT)
Type 2 Diabetes Mellitus (T2DM)

Additional relevant MeSH terms:

Obesity
Metabolic Diseases
Physiological Effects of Drugs
Glucose Intolerance
Diabetes Mellitus
Endocrine System Diseases
Overweight
Pharmacologic Actions
Body Weight

Signs and Symptoms
Hypoglycemic Agents
Hyperglycemia
Diabetes Mellitus, Type 2
Nutrition Disorders
Overnutrition
Glucose Metabolism Disorders
Rosiglitazone

ClinicalTrials.gov processed this record on February 08, 2010