The Liver Health Study for Patients With NAFLD

Study Overview
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Brief Summary
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The study will investigate whether the level of fat stored in the liver is related to the liver's ability to burn fat.

Detailed Description
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The study has two phases. In Phase I, liver samples from patients undergoing bariatric surgery or a diagnostic liver biopsy will be tested for the ability to burn fatty acids. In Phase II, patients with nonalcoholic fatty liver disease will participate in either a nine-month lifestyle treatment program or undergo standard care. The goal is to determine how weight loss and exercise improve liver health. Inpatient comprehensive metabolic tests are performed before and after the nine-months.

Official Title
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Nutrient Overload, Insulin Resistance, and Hepatic Mitochondrial Dysfunction

Conditions
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Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis, Obesity

Intervention / Treatment
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* Behavioral: Phase II: Lifestyle treatment
* Behavioral: Phase II: Control treatment
* Other: Phase I: Observational studies


Participation Criteria
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Eligibility Criteria
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For Phase I: Any patient scheduled to undergo bariatric surgery or a liver biopsy to diagnose nonalcoholic fatty liver disease. For Phase II: Only subjects who have had a diagnosis of nonalcoholic fatty liver disease and completed Phase I (and no subjects who have undergone bariatric surgery) Inclusion Criteria: Men and women (pre and post-menopausal) Overweight/obese with BMI ≥ 25.9 or < 50.0 kg/m2 Characteristics of the metabolic syndrome, pre-diabetes (fasting glucose 100-125 mg/dL or 2h glucose 140-200 mg/dL) or diabetes type 2, or undergoing bariatric surgery 22-65 years of age Sedentary, < 60 minutes per week of structured physical activity Alcohol intake< 20 g/d Exclusion Criteria: Having undergone bariatric surgery. Acute disease or advanced cardiac or renal disease, anticoagulation therapy, or any severe co-morbid condition limiting life expectancy < 1 years Other causes of hepatitis including hepatitis B & C, autoimmune hepatitis, hemochromatosis, celiac disease, Wilson's disease, alpha-1-antitrypsin deficiency, medication-induced hepatitis, any clinical or biochemical evidence of decompensated liver disease Use of steroids or other drugs that cause NAFLD Pregnant or trying to become pregnant Inability to exercise on a bike or treadmill

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: In Phase I, liver samples derived from patients undergoing either bariatric surgery or a liver biopsy to diagnose nonalcoholic fatty liver disease, are tested one time in vitro. There is no treatment in Phase I. In Phase II, only patients with nonalcoholic fatty liver disease (and not those who have had bariatric surgery) are eligible to go into a study in which they are randomly assigned to 1) a lifestyle treatment program or 2) a control group undergoing standard care. Allocation is 2:1 subjects in the treatment vs standard care groups. Thus, the arms are: Arm 1: Phase I studies with no treatment, only observational data generated in vitro from the liver samples Arm 2: Phase II lifestyle treatment Arm 3: Phase II control standard of care
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I: Observational studies<br>Patients are eligible who are undergoing either bariatric surgery or a liver biopsy for the diagnosis of nonalcoholic fatty liver disease | Other: Phase I: Observational studies<br>* The liver samples from patients undergoing bariatric surgery or a diagnostic liver biopsy will undergo in vitro assays to determine the capacity of the tissue to burn fat<br>|
| Experimental: Phase II: Lifestyle treatment<br>Subjects will undergo lifestyle modification to cause weight loss and improved fitness | Behavioral: Phase II: Lifestyle treatment<br>* Subjects will undergo energy restriction and exercise training over a 9 month period.<br>|
| Placebo Comparator: Phase II: Control treatment<br>Subjects will be given dietary advice and a stretching program. | Behavioral: Phase II: Control treatment<br>* Subjects will receive dietary advice and receive information on a stretching program.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver mitochondrial gene expression | Liver tissue will be tested in vitro to determine the abundance of transcript indicative of fat oxidation. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver mitochondrial fat oxidation | Liver tissue will be tested in vitro to determine its capacity to burn fat | 1 day | 
| Histology to determine the amount of fibrosis in the liver | Liver samples will be tested to determine the severity of liver disease and whether diet and exercise reduce liver fibrosis. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonalcoholic fatty liver, Exercise, Weight loss diet