NASH AMPK Exercise Dosing (AMPED) Trial

Overview

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

• Behavioral Exercise
  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).

Primary outcome measures

• Change in liver fat [Time frame: 16 weeks]

Secondary outcome measures (12)

• Hip/waist circumference [Time frame: 16 weeks]
• Body mass index [Time frame: 16 weeks]
• change in body composition [Time frame: 16 weeks]
• Insulin [Time frame: 16 weeks]
• Hemoglobin A1c [Time frame: 16 weeks]
• change in cholesterol and triglycerides levels (dyslipidemia) [Time frame: 16 weeks]
• Interleukin-6 [Time frame: 16 weeks]
• c-reactive protein [Time frame: 16 weeks]
• Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score [Time frame: 16 weeks]
• Enhance liver fibrosis (ELF) test [Time frame: 16 weeks]
• TIMP-1 [Time frame: 16 weeks]
• ProC3 [Time frame: 16 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Penn State Hershey Medical Center — Hershey

Identifiers

NCT: NCT04987879 · STUDY00018280 · K23DK131290

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗