Exercise Versus Diet in the Treatment of Nonalcoholic Fatty Liver Disease

Study Overview
=================
Brief Summary
-----------------
The central hypothesis of this proposal is that a reduction in hepatic mitochondrial function is the main pathophysiology behind NAFLD (Non-Alcoholic Fatty Liver Disease) and NASH (Non alcoholic steatohepatitis). The investigators further hypothesize that lifestyle modifications through aerobic exercise training without weight loss or diet-induced weight loss are effective in reducing NAFLD parameters by improving hepatic mitochondrial content and function in human subjects. The investigators propose a randomized, controlled human clinical trial to compare the effects of aerobic exercise training (without weight loss) versus diet-induced weight loss (without exercise) in individuals who have NAFLD or liver biopsy-confirmed NASH

Detailed Description
-----------------
Fatty Liver Disease) and NASH (Non alcoholic steatohepatitis). The investigators further hypothesize that lifestyle modifications through aerobic exercise training without weight loss or diet-induced weight loss are effective in reducing NAFLD parameters by improving hepatic mitochondrial content and function in human subjects. The investigators propose a randomized, controlled human clinical trial to compare the effects of aerobic exercise training (without weight loss) versus diet-induced weight loss (without exercise) in individuals who have NAFLD or liver biopsy-confirmed NASH

Official Title
-----------------
Exercise Versus Diet in the Treatment of Nonalcoholic Fatty Liver Disease

Conditions
-----------------
Non Alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Behavioral: Weight loss
* Behavioral: Exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: sedentary individual between age group 18-60 years old elevated Liver Function Tests (LFT's) with fatty liver on ultrasound and biopsy proven NASH Exclusion Criteria: significant history of alcohol consumption > 20 gm/day (> 2 drinks / day) evidence of other causes of hepatitis including positive screening B & C, autoimmune hepatitis, hemochromatosis, celiac disease, Wilson's disease, alpha 1 antitrypsin deficiency or medication-induced hepatitis Subjects with planned exercise > 30-60 minutes per week BMI < 25 or > 44 kg/m2 clinical or biochemical evidence of decompensated liver disease, advanced cardiac or renal disease changes in last 3 months the dose of oral hypoglycemic medication and statin, positive stress test pregnant women demented individuals who cannot give consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Weight loss<br>10% weight loss in 24 weeks time period through nutritional counseling. | Behavioral: Weight loss<br>* Nutritional counseling<br>|
| Active Comparator: Exercise without weight loss<br>24 weeks under direct supervision. | Behavioral: Exercise<br>* Under direct supervision<br>|
| No Intervention: Control<br>No change in usual exercise levels or food intake. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NASH ( Non alcoholic steatohepatitis score) on liver biopsy |  | baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver Function Tests | ALT/AST. | Baseline and 24 weeks | 
| DXA Scan |  | Baseline and 24 weeks | 
| Ultrasonographical changes in liver echotexture |  | Baseline and 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NAFLD, NASH, Weight loss, Exercise, NAS scores, Mitochondrial dysfunction