"ACTIV"Validation of a Paradigm for the Evaluation of Compounds That Activate Mitochondrial Biogenesis in Skeletal Muscle
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- To compare/ contrast the power of skeletal muscle biopsy vs. MRS to detect differences in mitochondrial capacity
研究概览
简要总结
The study is designed to compare muscle energy capacity in men with obesity or diabetes as compared to athletes. This study will also enable researchers to determine whether MRS can replace muscle biopsy for this type of assessment.
详细描述
Skeletal muscle mitochondrial defects are a sine qua non of insulin resistance in patients with type 2 diabetes mellitus (T2DM), obese and subjects with family history of T2DM (FH+). Exercise increases mitochondrial capacity whereas lipid infusion or high fat diet decreases genes involved in mitochondrial biogenesis. In this study 2 cohorts will be involved: Cohort I (athletes, T2DM and obese) and Cohort II (healthy with "FH+" or without "FH-" family history of T2DM). This randomized, parallel arm clinical trial will consist of 4 periods: screening, stabilization (3 days), baseline (for Cohort I and II) and exercise period (14 days, only for Cohort II). The overall objective of the study is to validate a paradigm for the evaluation of compounds and drugs that activate mitochondrial biogenesis in skeletal muscle. In Specific Aim 1 we will compare and contrast biopsy and MRS power to detect differences in mitochondrial capacity in 78 subjects: athletes (N=10), FH- (N=24), FH+ (N=24), obese (N=10) and T2DM (N=10). In Specific Aim 2 we will compare mitochondrial changes in response to exercise in subjects FH - vs. FH + subjects. In Specific Aim 3 we will determine if HFD impairs mitochondrial changes in response to exercise in FH+ subjects. In Specific Aim 4 we will determine the role of mitochondrial capacity in metabolic flexibility and insulin sensitivity in T2DM, obese, FH+, FH- and athlete subjects.
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
- None
入排标准
- 年龄范围
- 25 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •T2DM group:
- •Men aged 25-35
- •BMI > 30 kg/m2
- •Sedentary lifestyle determined by activity index questionnaire (not involved in regular exercise program) and accelerometer data.
- •Are willing to eat only foods provided by Pennington for the study period
- •Diagnosed with T2DM defined by one or more of the following:
- •fasting plasma glucose > 126 mg/dL at entry
- •a two-hour OGTT glucose > 200mg/dL
- •current medication for T2DM
- •Obese group:
- •Men aged 25-35
- •BMI > 30 kg/m2
- •Sedentary lifestyle activity index questionnaire (not involved in regular exercise program) and accelerometer data.
- •Are willing to eat only foods provided by Pennington for the study period
- •Men aged 25-35
- •One parent diagnosed with T2DM
- •fasting insulin > 10mIU/ml (> 50th %tile)
- •BMI between 22 and 30 kg/m2
- •Sedentary lifestyle activity index questionnaire (not involved in regular exercise program) and accelerometer data.
- •Are willing to exercise every day for the study period
- •Are willing to eat only foods provided by Pennington for the study period
- •Men aged 25-35
- •Parents and grandparents were not diagnosed with T2DM
- •Fasting insulin < 10mIU/ml (< 50th %tile)
- •BMI between 22 and 30 kg/m2
- •Sedentary lifestyle activity index questionnaire (not involved in regular exercise program) and accelerometer data.
- •Are willing to exercise for the study period
- •Are willing to eat only foods provided by Pennington for the study period
- •Athlete group:
- •Men aged 25-35
- •Maximal oxygen uptake > 60 ml/kg.min
- •Are engaged in minimum of 1.5 h of aerobic exercise 3 times/ week
- •Are willing to eat only foods provided by Pennington for the study period
排除标准
- •Abnormal resting or exercise ECG
- •Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp < 140/90 on medications)
- •Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
- •Alcohol or other drug abuse
- •Gait problems
- •Unwilling or unable to abstain from caffeine (48h) prior to metabolic rate measurements
- •Unwilling or unable to eat all study foods
- •Increased liver function tests at baseline (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal)
- •Metal objects that would interfere with the measurement of body composition /MRS such as implanted rods, surgical clips, etc
- •NYHA class III/IV CHF is an exclusionary cardiac condition
- •history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
- •varicose veins
- •major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
- •cancer (active malignancy with or without concurrent chemotherapy)
- •rheumatoid disease
- •bypass graft in limb
- •known genetic factor (Factor V Leiden, etc) or hypercoagulable state
- •diagnosed peripheral arterial or vascular disease, or intermittent claudication
- •family history of primary DVT or PE (pulmonary embolism)
- •peripheral neuropathy
结局指标
主要结局
To compare/ contrast the power of skeletal muscle biopsy vs. MRS to detect differences in mitochondrial capacity
时间窗: baseline and after intervention
次要结局
- To compare mitochondrial changes in response to exercise in subjects FH - vs. FH + subjects by skeletal muscle biopsy and MRS(baseline and after intervention)
- To determine if HFD impairs mitochondrial changes in response to exercise in the FH + group by muscle biopsy and MRS.(baseline and after intervention)
- To determine the role of mitochondrial capacity in metabolic flexibility and insulin sensitivity(baseline and after intervention)