Exercise for an Aging Liver (EXALIVER)

N/ANot Yet RecruitingNCT07467512

Consorcio Centro de Investigación Biomédica en Red (CIBER)40 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease

Interventions

ExerciseBEHAVIORAL

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 CareBEHAVIORAL

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

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change in hepatic fat content

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

Time frame: 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)

Time frame: 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.

Time frame: Change from baseline to 12 weeks.

Secondary Outcomes

Change in Enhanced Liver Fibrosis (ELF) Score

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.

Time frame: Change from baseline to 12 weeks

Change in Pro-C3 serum levels

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

Time frame: Change from baseline to 12 weeks

Change in NIS4 serum biomarker of liver fibrosis

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.

Time frame: Change from baseline to 12 weeks

Change in Metabolomics Advanced Steatohepatitis Fibrosis Score (MASEF)

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.

Time frame: Change from baseline to 12 weeks

Change in visceral adipose tissue

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

Time frame: Change from baseline to 12 weeks

Change in pancreatic fat content

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

Time frame: Change from baseline to 12 weeks

Change in abdominal subcutaneous adipose tissue

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

Time frame: Change from baseline to 12 weeks

Change in abdominal intermuscular fat content

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

Time frame: Change from baseline to 12 weeks

Change in abdominal intramuscular fat content

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

Time frame: Change from baseline to 12 weeks

Change in abdominal skeletal muscle tissue

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

Time frame: Change from baseline to 12 weeks

Change in values of fasting glucose

Fasting blood samples will be used to assess glucose

Time frame: Change from baseline to 12 weeks

Change in values of HbA1c

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

Time frame: Change from baseline to 12 weeks

Change in values of fasting insulin

Fasting blood samples will be used to assess insulin

Time frame: Change from baseline to 12 weeks

Change in levels of mean glucose (Continuous Glucose Monitoring)

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

Time frame: Change from baseline to 12 weeks.

Change in fasting lipid profile

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

Time frame: Change from baseline to 12 weeks

Change in alkaline phosphatase

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

Time frame: Baseline to 12 weeks

Change in alanine aminotransferase (ALT)

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

Time frame: Baseline to 12 weeks

Change in gamma-glutamyl transferase (GGT)

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

Time frame: Baseline to 12 weeks

Change in total bilirubin

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

Time frame: Baseline to 12 weeks

Change in creatinine

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

Time frame: Baseline to 12 weeks

Change in estimated glomerular filtration rate (eGFR)

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

Time frame: Baseline to 12 weeks

Change in values of C-reactive protein

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

Time frame: Change from baseline to 12 weeks

Change in values of interleukin 6

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

Time frame: Change from baseline to 12 weeks]

Change in blood pressure

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

Time frame: Change from baseline to 12 weeks

Change in waist, hip and neck circumference

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

Time frame: Change from baseline to 12 weeks.

Change in body weight

Body weight will be measured by a digital scale

Time frame: Change from baseline to 12 weeks

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

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

Time frame: Baseline to 12 weeks

Change in light physical activity

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

Time frame: Baseline to 12 weeks

Change in sedentary time

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

Time frame: Baseline to 12 weeks

Change in total activity counts

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

Time frame: Baseline to 12 weeks

Change in Subjective sleep quality

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.

Time frame: Baseline to 12 weeks

Change in total sleep time

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

Time frame: Baseline to 12 weeks

Change in Cardiorespiratory Fitness

Cardiorespiratory fitness measured by maximum treadmill test

Time frame: Change from baseline to 12 weeks

Change in Lower-body muscular performance

Lower body muscular performance measured by chair stand test.

Time frame: Change from baseline to 12 weeks

Change in Upper muscular strength

Upper body muscular strength measured by hand grip strength test.

Time frame: Change from baseline to 12 weeks

Change in Quality of life

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.

Time frame: Changes from baseline to 12-weeks

Change EuroQol Visual Analogue Scale (EQ-VAS) score

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.

Time frame: Changes from baseline to 12-weeks

Change in mid-thigh subcutaneous adipose tissue area

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

Time frame: Baseline to 12 weeks

Change in mid-thigh intramuscular fat content

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

Time frame: Baseline to 12 weeks

Change in mid-thigh intermuscular fat content

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

Time frame: Baseline to 12 weeks

Change in mid-thigh skeletal muscle cross-sectional area

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

Time frame: Baseline to 12 weeks

Exercise for an Aging Liver (EXALIVER)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts