Exercise for an Aging Liver (EXALIVER)

NCT07467512 | Not Yet Recruiting

• 1 other identifier: AG24_13
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; MASH - Metabolic Dysfunction-Associated Steatohepatitis; Liver Fibrosis/NASH

Outcome Measures

Primary Outcomes (3)

• Change in hepatic fat content

  Hepatic fat content will be determined by Proton Density Fat Fraction (PDFF) assessed by Magnetic Resonance Imaging (MRI)

  Change from baseline to 12 weeks

• Change in liver inflammation and fibrosis

  Iron-corrected T1 (cT1) will be determined though MRI to reflect liver tissue water content, correlating with histological features of fibroinflammation (ballooning, fibrosis, and NAS)

  Change from baseline to 12 weeks

• Change in liver stiffness

  Determined by vibration-controlled Transient Elastography (Fibroscan ®, VCTE). This is an ultrasound-based technique widely used in clinical practice to diagnose and monitor fibrosis progression. Liver stifness measurement increases with liver fibrosis.

  Change from baseline to 12 weeks.

Secondary Outcomes (41)

• Change in Enhanced Liver Fibrosis (ELF) Score

  Change from baseline to 12 weeks

• Change in Pro-C3 serum levels

  Change from baseline to 12 weeks

• Change in NIS4 serum biomarker of liver fibrosis

  Change from baseline to 12 weeks

• Change in Metabolomics Advanced Steatohepatitis Fibrosis Score (MASEF)

  Change from baseline to 12 weeks

• Change in visceral adipose tissue

  Change from baseline to 12 weeks

Study Arms (4)

Older adults with at risk MASH who exercise

EXPERIMENTAL

Older adults with Metabolic Dysfunction-Associated SteatoHepatitis aged 70 years or older who will complete the supervised 12-week exercise program.

Behavioral: Exercise

Middle-age adults with at risk MASH who exercise

EXPERIMENTAL

Middle-aged adults (40 to 60 years old) with at-risk metabolic dysfunction-associated SteatoHepatitis (MASH) who will complete a supervised 12-week exercise program

Behavioral: Exercise

Middle-age adults with MASLD who exercise

EXPERIMENTAL

Middle-aged adults (40 to 60 years old) with metabolic dysfunction-associated steatotic liver disease (MASLD) who will complete a supervised 12-week exercise program. This study arm will not recruit new participants. Instead, participants will be selected from a concluded clinical trial (NCT05897073; Study Arm: Experimental - Supervised Exercise Intervention), in which they completed the same exercise program and the same study outcome assessments of the present trial. These participants will be matched by sex, age and potential confounders to the individuals enrolled in the "Middle-aged adults with at-risk MASH who exercise" arm of the present study.

Behavioral: Exercise

Middle-age adults with MASLD receiving usual care

ACTIVE COMPARATOR

Middle-aged adults (40 to 60 years old) with metabolic dysfunction-associated steatotic liver disease (MASLD) who receive usual care. This study arm will not recruit new participants. Instead, participants will be selected from a concluded clinical trial (NCT05897073, Study Arm: No Intervention: Usual-care control group), in which they received usual care and the same study outcome assessments of the present trial. These participants will be matched by sex, age and potential confounders to the individuals enrolled in the "Middle-aged adults with at-risk MASH who exercise" arm of the present study.

Behavioral: Usual Care

Interventions

Exercise BEHAVIORAL

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) program to achieve a minimum of 135 minutes per week.

Middle-age adults with MASLD who exercise; Middle-age adults with at risk MASH who exercise; Older adults with at risk MASH who exercise

Usual Care BEHAVIORAL

Participants will receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion.

Middle-age adults with MASLD receiving usual care

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Consorcio Centro de Investigación Biomédica en Red (CIBER): lead
• Hospital General Universitario Gregorio Marañon: collaborator
• Universidad de Granada: collaborator
• Universidad Politecnica de Madrid: collaborator
• Universidad Complutense de Madrid: collaborator
• Instituto Mixto Universitario Deporte y Salud (iMUDS): collaborator

Study Sites (1)

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

MeSH Terms

Interventions

Exercise

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Jose Serra-Rexach, PhD

CONTACT

+34915868835; joseantonio.serra@salud.madrid.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: March 12, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)