Mechanisms of Skeletal Muscle Proteolysis With Ethanol Consumption: an Integrated Molecular Metabolic Approach
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Skeletal Muscle Autophagy
研究概览
简要总结
In this study we plan to demonstrate that ethanol induces skeletal muscle autophagy to degrade MAA adducts.
详细描述
Hypothesis
Ethanol mediated modification of skeletal muscle proteins to form MAA adducts that in turn induce skeletal muscle autophagy.
Patients with alcoholic steatosis, hepatitis and cirrhosis (n=10 each) will be recruited from the liver transplant nutrition clinic or the hepatology inpatient service and their body composition quantified using anthropometry, bioelectrical impedance analysis, CT image analysis and DEXA if available.
Control Subjects. Controls will be recruited by advertisement. All control subjects will have a normal clinical history, physical examination, and screening chemistries. They will not have any significant medical conditions requiring the use of medications. Their nutritional status within 20% of normal as defined by ideal body weight.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Alcoholic liver disease:
- •clinical, biochemical, imaging criteria and liver biopsy where available
- •Age 18 - 65 years old
- •Serum liver transaminases (i.e. ALT and AST) 40 IU/L
- •Normal liver ultrasound
- •Age 18 - 65 years old
排除标准
- •For both groups - alcoholic liver disease and controls:
- •Poorly controlled diabetes mellitus (HbA1C>9.5 g/dl)
- •Untreated Hyper- / hypo- thyroidism
- •Patients on dialysis, renal disease with serum creatinine 1.5 mg/dL
- •Active intravenous drug use
- •History of bowel surgery or gastric bypass surgery
- •Medications known to alter muscle protein metabolism (i.e. corticosteroids, tamoxifen, high-dose estrogen, testosterone or anabolic steroids)
- •Metastatic disease, Advanced cardiac or pulmonary disease
- •Pregnancy
- •Coagulopathy- INR >1.4 and platelet count <80,000/ml.
研究组 & 干预措施
Cirrhosis
This group will consist of 10 patients with cirrhosis. We anticipate a 50% difference in these patients and the controls in the autophagy readouts and muscle biopsies will be performed
干预措施: Biopsies (Other)
Alcoholic Steatosis
This group will have 10 patients with alcoholic steatosis which is milder disease and muscle biopsies will be performed
干预措施: Biopsies (Other)
Steatohepatitis
This group will have 10 patients with alcoholic steatohepatitis that have more severe necroinflammation in the liver but for a shorter duration of illness and muscle biopsies will be performed
干预措施: Biopsies (Other)
controls
This group will consist of 10 patients who are healthy and have no liver disease diagnosis and muscle biopsies will be performed
干预措施: Biopsies (Other)
结局指标
主要结局
Skeletal Muscle Autophagy
时间窗: 4 hours
We will measure Malonyldialdehyde Acetaldehyde protein adducts to see skeletal muscle proteolysis during a one time muscle biopsy
次要结局
未报告次要终点
研究者
Srinivasan Dasarathy
Staff Physician
The Cleveland Clinic