NASH AMPK Exercise Dosing (AMPED) Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Поведенческое 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).

Первичные конечные точки

• Change in liver fat [Срок оценки: 16 weeks]

Вторичные конечные точки (12)

• Hip/waist circumference [Срок оценки: 16 weeks]
• Body mass index [Срок оценки: 16 weeks]
• change in body composition [Срок оценки: 16 weeks]
• Insulin [Срок оценки: 16 weeks]
• Hemoglobin A1c [Срок оценки: 16 weeks]
• change in cholesterol and triglycerides levels (dyslipidemia) [Срок оценки: 16 weeks]
• Interleukin-6 [Срок оценки: 16 weeks]
• c-reactive protein [Срок оценки: 16 weeks]
• Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score [Срок оценки: 16 weeks]
• Enhance liver fibrosis (ELF) test [Срок оценки: 16 weeks]
• TIMP-1 [Срок оценки: 16 weeks]
• ProC3 [Срок оценки: 16 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Penn State Hershey Medical Center — Hershey

Идентификаторы

NCT: NCT04987879 · STUDY00018280 · K23DK131290

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗