Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07467512

Exercise for an Aging Liver (EXALIVER)

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

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

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location contact

Carlos Rodriguez Lopez, PhD

CONTACT

[email protected]

+34915868835

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

Primary outcomes

  1. Change in hepatic fat content

    Time frame: Change from baseline to 12 weeks

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

  2. Change in liver inflammation and fibrosis

    Time frame: Change from baseline to 12 weeks

    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)

  3. Change in liver stiffness

    Time frame: Change from baseline to 12 weeks.

    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.

Secondary outcomes

  1. Change in Enhanced Liver Fibrosis (ELF) Score

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to assess the Enhanced Liver Fibrosis (ELF) serum biomarker. The ELF score reflects the risk of advanced liver fibrosis, with higher values indicating higher risk.

  2. Change in Pro-C3 serum levels

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to asses Pro-C3 serum levels, a biomarker of liver fibrosis. Higher PRO-C3 levels indicate ongoing fibrotic activity

  3. Change in NIS4 serum biomarker of liver fibrosis

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to asses NIS4, a blood-based diagnostic tool designed to identify patients with at-risk MASH. It generates a composite score stratifying patients by risk.

  4. Change in Metabolomics Advanced Steatohepatitis Fibrosis Score (MASEF)

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to asses Metabolomics Advanced Steatohepatitis Fibrosis Score (MASEF) in serum samples. Is a proprietary algorithm that generates a numeric score that reflects the likelihood of a patient having at-risk MASH.

  5. Change in visceral adipose tissue

    Time frame: Change from baseline to 12 weeks

    Visceral adipose tissue will be assessed by Magnetic Resonance Imaging (MRI)

  6. Change in pancreatic fat content

    Time frame: Change from baseline to 12 weeks

    Pancreatic fat content will be assessed by Magnetic Resonance Imaging (MRI)

  7. Change in abdominal subcutaneous adipose tissue

    Time frame: Change from baseline to 12 weeks

    Abdominal subcutaneous adipose tissue will be assessed by Magnetic Resonance Imaging (MRI)

  8. Change in abdominal intermuscular fat content

    Time frame: Change from baseline to 12 weeks

    Abdominal intermuscular fat content will be assessed by Magnetic Resonance Imaging (MRI)

  9. Change in abdominal intramuscular fat content

    Time frame: Change from baseline to 12 weeks

    Abdominal intramuscular fat content will be assessed by Magnetic Resonance Imaging (MRI)

  10. Change in abdominal skeletal muscle tissue

    Time frame: Change from baseline to 12 weeks

    Abdominal skeletal muscle tissue will be assessed by Magnetic Resonance Imaging (MRI)

  11. Change in values of fasting glucose

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to assess glucose

  12. Change in values of HbA1c

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to assess HbA1c. Higher fasting HbA1C values indicates poorer glucemic control.

  13. Change in values of fasting insulin

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to assess insulin

  14. Change in levels of mean glucose (Continuous Glucose Monitoring)

    Time frame: Change from baseline to 12 weeks.

    24-hour, diurnal and nocturnal mean glucose over 14 days will be assessed by Continuous Glucose Monitoring during 2 weeks

  15. Change in fasting lipid profile

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to assess levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol an total cholesterol.

  16. Change in alkaline phosphatase

    Time frame: Baseline to 12 weeks

    Fasting blood samples will be used to assess serum alkaline phosphatase using standard clinical chemistry methods.

  17. Change in alanine aminotransferase (ALT)

    Time frame: Baseline to 12 weeks

    Fasting blood samples will be used to assess serum alanine aminotransferase (ALT) using standard clinical chemistry methods.

  18. Change in gamma-glutamyl transferase (GGT)

    Time frame: Baseline to 12 weeks

    Fasting blood samples will be used to assess serum gamma-glutamyl transferase (GGT) using standard clinical chemistry methods.

  19. Change in total bilirubin

    Time frame: Baseline to 12 weeks

    Fasting blood samples will be used to assess total serum bilirubin using standard clinical chemistry methods.

  20. Change in creatinine

    Time frame: Baseline to 12 weeks

    Fasting blood samples will be used to assess serum creatinine using standard clinical chemistry methods.

  21. Change in estimated glomerular filtration rate (eGFR)

    Time frame: Baseline to 12 weeks

    eGFR will be calculated from serum creatinine using a standard equation (e.g., CKD-EPI 2021), as implemented by the study laboratory.

  22. Change in values of C-reactive protein

    Time frame: Change from baseline to 12 weeks

    Fasting blood samples will be used to assess levels of C-reactive protein. Higher values indicate inflammation in the body.

  23. Change in values of interleukin 6

    Time frame: Change from baseline to 12 weeks]

    Fasting blood samples will be used to assess levels of interleukin 6. Higher basal levels often indicating greater inflammation or metabolic stress.

  24. Change in blood pressure

    Time frame: Change from baseline to 12 weeks

    Systolic and Diastolic blood pressure will be assessed by blood pressure monitor

  25. Change in waist, hip and neck circumference

    Time frame: Change from baseline to 12 weeks.

    Circumference will be assessed by measuring tape following the procedures outlined by the International Society for the Advancement of Kinanthropometry

  26. Change in body weight

    Time frame: Change from baseline to 12 weeks

    Body weight will be measured by a digital scale

  27. Change in moderate-to-vigorous physical activity (MVPA)

    Time frame: Baseline to 12 weeks

    Moderate-to-vigorous physical activity (minutes per day) will be estimated from wrist-worn accelerometry recorded over a 2-week monitoring period.

  28. Change in light physical activity

    Time frame: Baseline to 12 weeks

    Light physical activity (minutes per day) will be estimated from wrist-worn accelerometry recorded over a 2-week monitoring period.

  29. Change in sedentary time

    Time frame: Baseline to 12 weeks

    Sedentary time (minutes per day) will be estimated from wrist-worn accelerometry recorded over a 2-week monitoring period.

  30. Change in total activity counts

    Time frame: Baseline to 12 weeks

    Total activity counts per day will be estimated from wrist-worn accelerometry recorded over a 2-week monitoring period.

  31. Change in Subjective sleep quality

    Time frame: Baseline to 12 weeks

    Subjective sleep quality will be assessed by the Pittsburgh Sleep Quality Index (PSQI). Minimum value is 0 (never) and maximum value is 3 (3 or more times per week). Higher values mean a worse outcome.

  32. Change in total sleep time

    Time frame: Baseline to 12 weeks

    Total sleep time (minutes per night) will be estimated from wrist-worn accelerometry recorded over a 2-week monitoring period.

  33. Change in Cardiorespiratory Fitness

    Time frame: Change from baseline to 12 weeks

    Cardiorespiratory fitness measured by maximum treadmill test

  34. Change in Lower-body muscular performance

    Time frame: Change from baseline to 12 weeks

    Lower body muscular performance measured by chair stand test.

  35. Change in Upper muscular strength

    Time frame: Change from baseline to 12 weeks

    Upper body muscular strength measured by hand grip strength test.

  36. Change in Quality of life

    Time frame: Changes from baseline to 12-weeks

    Quality of life will be assessed by the Rand Short Form 36 (SF-36). This questionnaire provides an score ranged from 0 to 100. Higher values mean better quality of life.

  37. Change EuroQol Visual Analogue Scale (EQ-VAS) score

    Time frame: Changes from baseline to 12-weeks

    The EQ-VAS is a vertical 0-100 scale used in the EuroQol EQ-5D instrument to measure a patient's self-rated, current overall health. It ranges from 0 (worst imaginable health) to 100 (best imaginable health), allowing patients to quantify their perceived health status.

  38. Change in mid-thigh subcutaneous adipose tissue area

    Time frame: Baseline to 12 weeks

    Mid-thigh subcutaneous adipose tissue area will be quantified from segmented magnetic resonance imaging (MRI) slices.

  39. Change in mid-thigh intramuscular fat content

    Time frame: Baseline to 12 weeks

    Mid-thigh intramuscular fat content will be quantified from segmented magnetic resonance imaging (MRI) slices.

  40. Change in mid-thigh intermuscular fat content

    Time frame: Baseline to 12 weeks

    Mid-thigh intermuscular fat content will be quantified from segmented magnetic resonance imaging (MRI) slices.

  41. Change in mid-thigh skeletal muscle cross-sectional area

    Time frame: Baseline to 12 weeks

    Mid-thigh skeletal muscle cross-sectional area will be quantified from segmented magnetic resonance imaging (MRI) slices.

Study contacts

Contact information is provided by the study sponsor or research team.

Jose Serra-Rexach, PhD

CONTACT

[email protected]

+34915868835

Sponsors and collaborators

Lead sponsor

Consorcio Centro de Investigación Biomédica en Red (CIBER)

Other Gov

Collaborators

  • Hospital General Universitario Gregorio Marañon
  • Instituto Mixto Universitario Deporte y Salud (iMUDS)
  • Universidad Complutense de Madrid
  • Universidad Politecnica de Madrid
  • Universidad de Granada

Registry information

Official study title

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

Acronym: EXALIVER

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Mar 12, 2026
Registry last updated
Mar 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.