NASH AMPK Exercise Dosing (AMPED) Trial (AMPED)

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.

Study Overview

• Status: Recruiting
• Conditions: NAFLD
• Intervention / Treatment: Behavioral: Exercise

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 Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Breianna L Hummer, MS; Phone Number: 320223 7175310003; Email: bhummer@pennstatehealth.psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Hershey Medical Center
      • Contact: Breianna L Hummer, MS; Phone Number: 320223 7175310003; Email: bhummer@pennstatehealth.psu.edu
      • Principal Investigator: Christopher Sciamanna, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Arm 1; 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.	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).; Other Names: Physical activity
Experimental: Exercise Arm 2; 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.	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).; Other Names: Physical activity
No Intervention: Standard of Care; This group will receive best NASH clinical practices counseling at baseline and end-of-trial in accordance with NAFLD clinical practice guidelines and be reinforced by handouts from the American Liver Foundation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver fat	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.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hip/waist circumference	change in Hip/waist circumference	16 weeks
Body mass index	change in body mass index	16 weeks
change in body composition	change in body composition as measured by Dual-energy X-ray absorptiometry (DXA scan) across different doses of exercise in patients with NASH.	16 weeks
Insulin	change in insulin	16 weeks
Hemoglobin A1c	change in Hemoglobin A1c	16 weeks
change in cholesterol and triglycerides levels (dyslipidemia)	change in cholesterol and triglycerides levels (dyslipidemia) as measured by clinical labs.	16 weeks
Interleukin-6	change in Interleukin-6	16 weeks
c-reactive protein	change in c-reactive protein	16 weeks
Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score	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	16 weeks
Enhance liver fibrosis (ELF) test	change in Enhance liver fibrosis (ELF) test	16 weeks
TIMP-1	change in TIMP-1	16 weeks
ProC3	change in ProC3	16 weeks
Adiponectin	change in Adiponectin	16 weeks
Fibroblast Growth Factor (FGF) 21	change in Fibroblast Growth Factor (FGF) 21	16 weeks
Change in stiffness of the liver	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.	16 weeks
Liver glycogen	change in liver glycogen	16 weeks

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Christopher Sciamanna, MD, Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): July 15, 2026

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: STUDY00018280; K23DK131290 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No