NASH AMPK Exercise Dosing (AMPED) Trial

Not Applicable

Recruiting

• Conditions: NAFLD
• Interventions: Behavioral: Exercise

• Registration Number: NCT04987879
• Lead Sponsor: Milton S. Hershey Medical Center

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.

Study Timeline

• Study First Submitted: 2021-07-13
• Study First Submitted QC: 2021-07-23
• Study First Posted: 2021-08-03
• Study Start: 2022-08-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-13
• Primary Completion: 2025-10-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exercise Arm 1	Exercise	Aerobic exercise will 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 and dynamic exercises. A 5-min walking cool down will end the session. The training dose for this arm is 750 MET-min/wk for 3-5 days per week, 22-45 minutes per session at a moderate to vigorous intensity. The exercise can be completed in person or virtually.
Exercise Arm 2	Exercise	Aerobic exercise will 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 and dynamic exercises. A 5-min walking cool down will end the session. The training dose for this arm is 1,000 MET-min/wk for 3-5 days per week, 30-60 minutes per session at a moderate to vigorous intensity. The exercise can be completed in person or virtually.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
Enhance liver fibrosis (ELF) test	16 weeks	change in Enhance liver fibrosis (ELF) test
Hip/waist circumference	16 weeks	change in Hip/waist circumference
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
TIMP-1	16 weeks	change in TIMP-1
Body mass index	16 weeks	change in body mass index
c-reactive protein	16 weeks	change in c-reactive protein
ProC3	16 weeks	change in ProC3
Adiponectin	16 weeks	change in Adiponectin
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.
Insulin	16 weeks	change in insulin
change in cholesterol and triglycerides levels (dyslipidemia)	16 weeks	change in cholesterol and triglycerides levels (dyslipidemia) as measured by clinical labs.
Liver glycogen	16 weeks	change in liver glycogen
Hemoglobin A1c	16 weeks	change in Hemoglobin A1c
Interleukin-6	16 weeks	change in Interleukin-6
Fibroblast Growth Factor (FGF) 21	16 weeks	change in Fibroblast Growth Factor (FGF) 21

Trial Locations

Locations (1)

Penn State Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States