NASH AMPK Exercise Dosing (AMPED) Trial

NAFLD Clinical Trial

— AMPED  

Official title:

NASH AMPK Exercise Dosing (AMPED) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04987879
• Other study ID #: STUDY00018280
• Status: Recruiting
• Phase: N/A
• Start date: August 30, 2022
• Est. completion date: June 1, 2026

Study information

• Verified date: November 2023
• Source: Milton S. Hershey Medical Center
• Contact: Breianna L Hummer, MS
• Phone: 7175310003
• Email: bhummer[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 1, 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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.

Related Conditions & MeSH terms

• NAFLD

Intervention

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).

Locations

Country	Name	City	State
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

Outcome

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