Ethanol Induces Skeletal Muscle Autophagy

NeuroTherapia, Inc.

Status: Enrolling

Conditions: Alcoholic Liver Disease

Treatments: Other: Biopsies

Study type: Observational

Funder types: Other

Identifiers

NCT03209791

14-1287

Details and patient eligibility

About

In this study we plan to demonstrate that ethanol induces skeletal muscle autophagy to degrade MAA adducts.

Full description

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Alcoholic liver disease:

• clinical, biochemical, imaging criteria and liver biopsy where available
• Age 18 - 65 years old

Controls:

• Serum liver transaminases (i.e. ALT and AST) 40 IU/L
• Normal liver ultrasound
• Age 18 - 65 years old

Exclusion criteria

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.

Trial design

40 participants in 4 patient groups

Alcoholic Steatosis

Description:

This group will have 10 patients with alcoholic steatosis which is milder disease and muscle biopsies will be performed

Treatment:

Other: Biopsies

Cirrhosis

Description:

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

Treatment:

Other: Biopsies

Steatohepatitis

Description:

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

Treatment:

Other: Biopsies

controls

Description:

This group will consist of 10 patients who are healthy and have no liver disease diagnosis and muscle biopsies will be performed

Treatment:

Other: Biopsies