Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Percentage of Subjects Who Converted Impaired Glucose Tolerance (IGT) to Normal Glucose Tolerance (NGT)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Rosiglitazone (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Subjects Who Converted Impaired Glucose Tolerance (IGT) to Normal Glucose Tolerance (NGT)
时间窗: 4 months
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)
时间窗: 4 months
It refers to the percent changes of hepatic fat content.
Mean Percent Change From Baseline in Whole-body Insulin Sensitivity
时间窗: 4 months
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
时间窗: 4 months
This describes the percent changes of the ratio between visceral and subcutaneous abdominal fat.
次要结局
- Mean Percent Change From Baseline in Adiponectin(4 months)
研究者
Sonia Caprio
Principal Investigator
Yale University