Evaluation of the Impact of Physical Exercise on Metabolic Dysfunction-associated Steatotic Liver Disease in the Elderly
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in hepatic fat content
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Older adults with at risk MASH who exercise
Older adults with Metabolic Dysfunction-Associated SteatoHepatitis aged 70 years or older who will complete the supervised 12-week exercise program.
干预措施: Exercise (Behavioral)
Middle-age adults with at risk MASH who exercise
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
干预措施: Exercise (Behavioral)
Middle-age adults with MASLD who exercise
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.
干预措施: Exercise (Behavioral)
Middle-age adults with MASLD receiving usual care
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.
干预措施: Usual Care (Behavioral)
结局指标
主要结局
Change in hepatic fat content
时间窗: Change from baseline to 12 weeks
Hepatic fat content will be determined by Proton Density Fat Fraction (PDFF) assessed by Magnetic Resonance Imaging (MRI)
Change in liver inflammation and fibrosis
时间窗: 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)
Change in liver stiffness
时间窗: 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.
次要结局
- 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)
- Change in pancreatic fat content(Change from baseline to 12 weeks)
- Change in abdominal subcutaneous adipose tissue(Change from baseline to 12 weeks)
- Change in abdominal intermuscular fat content(Change from baseline to 12 weeks)
- Change in abdominal intramuscular fat content(Change from baseline to 12 weeks)
- Change in abdominal skeletal muscle tissue(Change from baseline to 12 weeks)
- Change in values of fasting glucose(Change from baseline to 12 weeks)
- Change in values of HbA1c(Change from baseline to 12 weeks)
- Change in values of fasting insulin(Change from baseline to 12 weeks)
- Change in levels of mean glucose (Continuous Glucose Monitoring)(Change from baseline to 12 weeks.)
- Change in fasting lipid profile(Change from baseline to 12 weeks)
- Change in alkaline phosphatase(Baseline to 12 weeks)
- Change in alanine aminotransferase (ALT)(Baseline to 12 weeks)
- Change in gamma-glutamyl transferase (GGT)(Baseline to 12 weeks)
- Change in total bilirubin(Baseline to 12 weeks)
- Change in creatinine(Baseline to 12 weeks)
- Change in estimated glomerular filtration rate (eGFR)(Baseline to 12 weeks)
- Change in values of C-reactive protein(Change from baseline to 12 weeks)
- Change in values of interleukin 6(Change from baseline to 12 weeks])
- Change in blood pressure(Change from baseline to 12 weeks)
- Change in waist, hip and neck circumference(Change from baseline to 12 weeks.)
- Change in body weight(Change from baseline to 12 weeks)
- Change in moderate-to-vigorous physical activity (MVPA)(Baseline to 12 weeks)
- Change in light physical activity(Baseline to 12 weeks)
- Change in sedentary time(Baseline to 12 weeks)
- Change in total activity counts(Baseline to 12 weeks)
- Change in Subjective sleep quality(Baseline to 12 weeks)
- Change in total sleep time(Baseline to 12 weeks)
- Change in Cardiorespiratory Fitness(Change from baseline to 12 weeks)
- Change in Lower-body muscular performance(Change from baseline to 12 weeks)
- Change in Upper muscular strength(Change from baseline to 12 weeks)
- Change in Quality of life(Changes from baseline to 12-weeks)
- Change EuroQol Visual Analogue Scale (EQ-VAS) score(Changes from baseline to 12-weeks)
- Change in mid-thigh subcutaneous adipose tissue area(Baseline to 12 weeks)
- Change in mid-thigh intramuscular fat content(Baseline to 12 weeks)
- Change in mid-thigh intermuscular fat content(Baseline to 12 weeks)
- Change in mid-thigh skeletal muscle cross-sectional area(Baseline to 12 weeks)