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| Name | Class |
|---|---|
| Hospital General Universitario Gregorio Marañon | OTHER |
| Universidad de Granada | OTHER |
| Universidad Politecnica de Madrid | OTHER |
| Universidad Complutense de Madrid |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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 |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Change from baseline to 12 weeks |
| Change in Pro-C3 serum levels |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jose Serra-Rexach, PhD | Contact | +34915868835 | joseantonio.serra@salud.madrid.es |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital General Universitario Gregorio Marañon | Madrid | 28007 | Spain |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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| OTHER |
| Instituto Mixto Universitario Deporte y Salud (iMUDS) | UNKNOWN |
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| 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. |
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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 |
| 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. | 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. | Change from baseline to 12 weeks |
| Change in visceral adipose tissue | Visceral adipose tissue will be assessed by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 weeks |
| Change in pancreatic fat content | Pancreatic fat content will be assessed by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 weeks |
| Change in abdominal subcutaneous adipose tissue | Abdominal subcutaneous adipose tissue will be assessed by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 weeks |
| Change in abdominal intermuscular fat content | Abdominal intermuscular fat content will be assessed by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 weeks |
| Change in abdominal intramuscular fat content | Abdominal intramuscular fat content will be assessed by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 weeks |
| Change in abdominal skeletal muscle tissue | Abdominal skeletal muscle tissue will be assessed by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 weeks |
| Change in values of fasting glucose | Fasting blood samples will be used to assess glucose | 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. | Change from baseline to 12 weeks |
| Change in values of fasting insulin | Fasting blood samples will be used to assess insulin | 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 | 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. | 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. | 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. | 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. | Baseline to 12 weeks |
| Change in total bilirubin | Fasting blood samples will be used to assess total serum bilirubin using standard clinical chemistry methods. | Baseline to 12 weeks |
| Change in creatinine | Fasting blood samples will be used to assess serum creatinine using standard clinical chemistry methods. | 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. | 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. | 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. | Change from baseline to 12 weeks] |
| Change in blood pressure | Systolic and Diastolic blood pressure will be assessed by blood pressure monitor | 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 | Change from baseline to 12 weeks. |
| Change in body weight | Body weight will be measured by a digital scale | 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. | 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. | 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. | 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. | 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. | 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. | Baseline to 12 weeks |
| Change in Cardiorespiratory Fitness | Cardiorespiratory fitness measured by maximum treadmill test | Change from baseline to 12 weeks |
| Change in Lower-body muscular performance | Lower body muscular performance measured by chair stand test. | Change from baseline to 12 weeks |
| Change in Upper muscular strength | Upper body muscular strength measured by hand grip strength test. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline to 12 weeks |