NASH AMPK Exercise Dosing (AMPED) Trial

Penn State Health

Status: Enrolling

Conditions: NAFLD

Treatments: Behavioral: Exercise

Study type: Interventional

Funder types: Other

Identifiers

NCT04987879

STUDY00018280

K23DK131290 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 69 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 3 patient groups

Exercise Arm 1

Experimental group

Description:

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.

Treatment:

Behavioral: Exercise

Exercise Arm 2

Experimental group

Description:

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.

Treatment:

Behavioral: Exercise

Standard of Care

No Intervention group

Description:

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.