NAFLD
Conditions
Brief summary
There is no known cure or regulatory agency approved drug therapy for nonalcoholic fatty liver disease (NAFLD), the leading cause of liver disease worldwide, and its progressive type, NASH. This places increased importance on using exercise to treat NAFLD. While physical activity is recommended for all with NAFLD, how to best prescribe exercise as a specific treatment remains unknown, including what dose of exercise is most effective.
Detailed description
The mechanism explaining how exercise training benefits patients with NAFLD and NASH is unclear. The AMPK pathway may be responsible for the benefits seen with exercise training because: 1) AMPK has a liver-specific role in hepatic de novo lipogenesis and fatty acid oxidation, 2) AMPK activity is abnormally low in NAFLD and 3) NAFLD animal models demonstrate exercise changes the liver-specific AMPK pathway, leading to less liver fat accumulation by reducing lipogenesis and increasing fatty acid oxidation (This has not been studied in patients). Importantly, exercise-induced AMPK activation appears to be dose dependent.
Interventions
BEHAVIORALExercise
Aerobic exercise can be completed by walking, jogging or running or by using cardio equipment (e.g., recumbent bike). Each session will begin with a warm-up with walking (30-40% target HR for 5-min) and dynamic exercises (knee-to-chest, 10-yd lateral shuffle, bent over twist, calf sweeps, leg swings). A 5-min walking cool down will end the session (30-40% target HR).
Sponsors
Milton S. Hershey Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-69 years * Sedentary \[\<90 min/wk of exercise identified by the Get Active Questionnaire (GAQ) * BMI \>25kg/m2 * Liver biopsy within six months prior to enrollment showing: * NASH defined by NASH Clinical Research Network (CRN) histology scoring system (NAS) \>4 and MRI-PDFF \>5% and; * Liver fibrosis stage 1-3
Exclusion criteria
* Active cardiac symptoms * Body mass index (BMI) \>45kg/m2 * Cancer that is active * Inability to walk \>2 blocks * Institutionalized/prisoner * Other liver disease * Pregnancy * Secondary hepatic steatosis * Severe comorbidities * AUDIT-C questionnaire identified significant alcohol use * Substance abuse/active smoking * Uncontrolled diabetes (changes in drug dosing over previous three months or A1c \>9%) * GAQ response indicates exercise may be unsafe.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in liver fat | 16 weeks | Degree of liver fat change as measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF) across different doses of exercise in patients with NASH. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Enhance liver fibrosis (ELF) test | 16 weeks | change in Enhance liver fibrosis (ELF) test |
| TIMP-1 | 16 weeks | change in TIMP-1 |
| ProC3 | 16 weeks | change in ProC3 |
| Adiponectin | 16 weeks | change in Adiponectin |
| Fibroblast Growth Factor (FGF) 21 | 16 weeks | change in Fibroblast Growth Factor (FGF) 21 |
| Change in stiffness of the liver | 16 weeks | Change in stiffness of the liver as measured by the technique of transient elastography, a non-invasive test to stage the severity of liver disease. |
| Liver glycogen | 16 weeks | change in liver glycogen |
| Hip/waist circumference | 16 weeks | change in Hip/waist circumference |
| Body mass index | 16 weeks | change in body mass index |
| change in body composition | 16 weeks | change in body composition as measured by Dual-energy X-ray absorptiometry (DXA scan) across different doses of exercise in patients with NASH. |
| Insulin | 16 weeks | change in insulin |
| Hemoglobin A1c | 16 weeks | change in Hemoglobin A1c |
| change in cholesterol and triglycerides levels (dyslipidemia) | 16 weeks | change in cholesterol and triglycerides levels (dyslipidemia) as measured by clinical labs. |
| Interleukin-6 | 16 weeks | change in Interleukin-6 |
| Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score | 16 weeks | change in NAFLD Fibrosis Score which estimates amount of scarring in the liver based on several laboratory tests. NAFLD Score Correlated Fibrosis Severity \< -1.455 F0-F2 -1.455 - 0.675 Indeterminant score \> 0.675 F3-F4 Fibrosis Severity Scale F0 = no fibrosis F1 = mild fibrosis F2 = moderate fibrosis F3 = severe fibrosis F4 = cirrhosis |
| c-reactive protein | 16 weeks | change in c-reactive protein |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristopher Sciamanna, MD
Milton S. Hershey Medical Center
Outcome results
None listed