A Randomized Trial Using ADI-PEG20 to Improve Insulin- and Energy Homeostasis in Adolescents With Obesity
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change in insulin sensitivity
研究概览
简要总结
Th purpose of this study is to determine whether ADI-PEG20 (PEGylated arginine deiminase), an arginine catabolizing enzyme preparation, improves insulin sensitivity, mitochondrial respiration, and energy utilization in adolescents with prediabetes.
详细描述
Obesity, insulin resistance, and their complications are major causes of morbidity and mortality in children, adolescents, and adults. Although caloric restriction is an effective treatment, intensive lifestyle changes are rarely durable. The investigators and others have shown that: (i.) fasting incites arginine catabolism, and forced arginine catabolism recapitulates several therapeutic effects of fasting, (ii.) exogenous, forced arginine catabolism improves metabolic health, and (iii.) ADI-PEG20 (PEGylated arginine deiminase) is an arginine catabolizing enzyme preparation that improves insulin sensitivity, mitochondrial respiration, and energy utilization in obese mice. The study will determine whether ADI-PEG20 also exerts beneficial effects on metabolic healthy in people. The investigators will perform a 12-week, randomized, double-blind, placebo-controlled trial in boys and girls with pre-diabetes to evaluate the efficacy of ADI-PEG20 treatment on: 1) body composition; 2) resting energy expenditure; 3) multi-organ insulin sensitivity; 3) β-cell function; and 4) muscle mitochondrial function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 22 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age: ≥18 and ≤22 years;
- •BMI 25.0 - 44.9 kg/m2;
- •Prediabetes, defined as fasting plasma glucose of ≥100 mg/dL, or HbA1C ≥5.7%, or HOMA-IR ≥2.5.
排除标准
- •HbA1C ≥6.5%;
- •Intolerance or allergies to ingredients in ADI-PEG20 or placebo;
- •Taking dietary supplements or medications known to affect our study outcomes;
- •Evidence of significant organ system dysfunction or diseases,
- •Metallic implants, which would preclude MRI
研究组 & 干预措施
ADI-PEG20
ADI-PEG20 (ADI-PEG20 is arginine deiminase (ADI) conjugated to polyethylene glycol (PEG) of 20,000 molecular weight) will be weekly intramuscularly at a dose of 18 mg/m2 body surface area/week for 8-week.
干预措施: ADI-PEG20 (Biological)
Placebo
Will be weekly intramuscularly for 8-week
干预措施: Placebo (Other)
结局指标
主要结局
Change in insulin sensitivity
时间窗: Baseline and 8 weeks of ADI-PEG20 or placebo
Insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
次要结局
- Change in oral glucose tolerance(Baseline and 8 weeks of ADI-PEG20 or placebo)
- Change in β-cell function(Baseline and 8 weeks of ADI-PEG20 or placebo)
- Change in resting energy expenditure(Baseline and 8 weeks of ADI-PEG20 or placebo)
- Change in muscle mitochondrial respiration(Baseline and 8 weeks of ADI-PEG20 or placebo)
- Change in intrahepatic triglyceride content(Baseline and 8 weeks of ADI-PEG20 or placebo)