Exercise for an Aging Liver (EXALIVER)

Official title

Evaluation of the Impact of Physical Exercise on Metabolic Dysfunction-associated Steatotic Liver Disease in the Elderly

Overview

The goal of this clinical trial is to learn how physical exercise affects liver health in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) or at-risk metabolic dysfunction-associated steatohepatitis (MASH); comparing responses between middle-aged adults (40-60 years old) and older adults (70 years and older) of any sex, as well as between participants with low-risk MASLD and high-risk MASH. The main question it aims to answer is: Could an exercise program reduce liver fat, inflammation and fibrosis, regardless of age and disease severity? Researchers will compare 4 different groups: A) older adults with at risk MASH who will exercise B) middle-aged people with at risk MASH who will exercise C) middle-aged people with low-risk MASLD who will exercise D) middle-aged people with low-risk MASLD who will not exercise, receiving usual care. Participants in the exercise groups will take part in a supervised 12-week exercise program that includes both strength and aerobic training, completed twice a week. All participants, including those receiving usual care, will have health asssessments before and after the 12-week period to measure changes in liver health.

Interventions

• Behavioral Exercise
  The exercise intervention will include 2 days/week of supervised moderate-high intensity resistance training (rating perceived exertion \>7, circuit-training, upper and lower body exercises involving major muscle groups) and high-intensity interval training (4 sets of 4-minute intervals at \>85% peak heat rate with 4-minute of active recovery at 50-65% peak heat rate, uphill treadmill walking). Moreover, participants will receive an individualized moderate-intensity goal-setting aerobic (walking
• Behavioral Usual Care
  Participants will receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion.

Primary outcome measures

• Change in hepatic fat content [Time frame: Change from baseline to 12 weeks]
• Change in liver inflammation and fibrosis [Time frame: Change from baseline to 12 weeks]
• Change in liver stiffness [Time frame: Change from baseline to 12 weeks.]

Secondary outcome measures (12)

• Change in Enhanced Liver Fibrosis (ELF) Score [Time frame: Change from baseline to 12 weeks]
• Change in Pro-C3 serum levels [Time frame: Change from baseline to 12 weeks]
• Change in NIS4 serum biomarker of liver fibrosis [Time frame: Change from baseline to 12 weeks]
• Change in Metabolomics Advanced Steatohepatitis Fibrosis Score (MASEF) [Time frame: Change from baseline to 12 weeks]
• Change in visceral adipose tissue [Time frame: Change from baseline to 12 weeks]
• Change in pancreatic fat content [Time frame: Change from baseline to 12 weeks]
• Change in abdominal subcutaneous adipose tissue [Time frame: Change from baseline to 12 weeks]
• Change in abdominal intermuscular fat content [Time frame: Change from baseline to 12 weeks]
• Change in abdominal intramuscular fat content [Time frame: Change from baseline to 12 weeks]
• Change in abdominal skeletal muscle tissue [Time frame: Change from baseline to 12 weeks]
• Change in values of fasting glucose [Time frame: Change from baseline to 12 weeks]
• Change in values of HbA1c [Time frame: Change from baseline to 12 weeks]

Eligibility criteria

Inclusion criteria

• Middle-aged adults (40 to 60 years old) and older adults (aged 70 years or older)
• People diagnosed with Metabolic Disfunction-Associated Steatotic Liver Disease (MASLD); defined as the presence of hepatic steatosis (≥5% fat content) in conjunction with at least one cardiometabolic risk factor (overweight or obesity, dysglycaemia or Type II diabetes, elevated plasma triglycerides, reduced HDL-cholesterol or high blood preassure) with no other discernable cause.
• People diagnosed with at-risk Metabolic Disfunction-Associated SteatoHepatitis (MASH) according to the following criteria: I) a positive liver biopsy (NAS score ≥ 4 points (with at least one point in each of the components of the score: steatosis, lobular inflammation and ballooning, AND significant (F2) or advanced (F3) fibrosis), or II) a FAST score >0.65.

Exclusion criteria

• Descompensated cirrhosis or end-stage liver disease.
• Other causes of liver disease, such as alcohol abuse or drug-induced, virus-related, or hereditary disease.
• History of a major adverse cardiovascular event, clinically significant kidney, endocrine, or neurological disease, bariatric surgery, HIV/AIDS, known inflammatory and/or rheumatologic disease, cancer, or other medical condition in which exercise is absolute contraindicated.
• Recent or planned major surgery, as well as anticancer therapies.
• Participating in a weight loss, a weight-management program or a supervised exercise program (more than 30 minutes three times per week, or 45 minutes twice a week, moderate/vigorous intensity).
• Body weight instability. Participants must have maintained the body weight registered at screening visit (tolerance: 5%) for more than 3 months.
• Regular use of medication or compounds that may affect study outcomes based on research staff criteria.
• Pregnancy and lactation or planned pregnancy (within the study period).
• Frequent travel over time zones during the study period.
• Fear of needles and claustrophobia to magnetic resonance imaging (MRI).
• Low physical function (ie, ambulation dependency)
• Being unable to understand and to accept the instructions or the study objectives and protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital General Universitario Gregorio Marañon — Madrid

Identifiers

NCT: NCT07467512 · AG24_13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗