Clinical trial NCT04987879: NASH AMPK Exercise Dosing (AMPED) Trial
Official title: NASH AMPK Exercise Dosing (AMPED) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: NAFLD
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2021-08-03
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in liver fat
timeFrame: 16 weeks
Secondary outcomes:
measure: Hip/waist circumference
timeFrame: 16 weeks
measure: Body mass index
timeFrame: 16 weeks
measure: change in body composition
timeFrame: 16 weeks
measure: Insulin
timeFrame: 16 weeks
measure: Hemoglobin A1c
timeFrame: 16 weeks
measure: change in cholesterol and triglycerides levels (dyslipidemia)
timeFrame: 16 weeks
measure: Interleukin-6
timeFrame: 16 weeks
measure: c-reactive protein
timeFrame: 16 weeks
measure: Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score
timeFrame: 16 weeks
measure: Enhance liver fibrosis (ELF) test
timeFrame: 16 weeks
measure: TIMP-1
timeFrame: 16 weeks
measure: ProC3
timeFrame: 16 weeks
measure: Adiponectin
timeFrame: 16 weeks
measure: Fibroblast Growth Factor (FGF) 21
timeFrame: 16 weeks
measure: Change in stiffness of the liver
timeFrame: 16 weeks
measure: Liver glycogen
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Jonathan G Stine
role: PRINCIPAL_INVESTIGATOR
References: