Impact of Circadian Exercise on Metabolic Dysfunction-Associated Steatotic Liver Disease in Postmenopausal Women
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Hepatic fat content
研究概览
简要总结
Type of Study: Clinical Trial
Goal: The goal of this clinical trial is to investigate how performing exercise at different times of day (morning vs. evening) affects liver fat, cardiometabolic health, and gut microbiota in postmenopausal women.
Participant Population/Health Conditions: The study will involve 63 sedentary postmenopausal women (aged 45-75) diagnosed with metabolic dysfunction-associated steatotic liver disease.
Main Questions: The main questions this study aims to answer are:
- Does morning exercise reduce hepatic fat more effectively than evening exercise?
- How does time-of-day-specific exercise influence cardiometabolic markers?
- Do changes in gut microbiota contribute to the metabolic effects of exercise timing?
Participants Will:
Be randomized into one of three groups: morning exercise, evening exercise, or a usual-care control group.
Follow the assigned regimen for 12 weeks. The exercise groups will perform supervised aerobic and resistance training three times per week.
Provide blood, stool, and imaging data before and after the intervention to determine the effects of the intervention.
Comparison Group:
Researchers will compare the effects of morning vs. evening exercise (and usual care) on hepatic fat reduction and cardiometabolic improvement, as well as changes in gut microbiota.
详细描述
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one in three adults and is a major contributor to the growing burden of cardiometabolic disease. Exercise is one of the most effective interventions for improving cardiometabolic health, reducing hepatic fat, and enhancing metabolic flexibility. However, the timing of exercise -a modifiable behavioral factor- may play a crucial yet underexplored role in determining its physiological benefits.
Preclinical studies have shown that circadian rhythms regulate key metabolic processes, including lipid metabolism and glucose homeostasis. Moreover, recent findings suggest that exercise performed at different times of day may elicit different responses, influencing the regulation of hepatic fat and systemic inflammation. These effects may be mediated, in part, through gut microbiota, which modulate host metabolism via the gut-liver axis. However, the interaction between exercise timing and gut microbiota in human physiology -particularly in women- remains poorly understood.
This knowledge gap is particularly critical in postmenopausal women, a population that experiences profound metabolic changes due to hormonal decline, including increased hepatic and visceral fat, chronic inflammation, and reduced insulin sensitivity. These alterations significantly elevate the risk for MASLD and other cardiometabolic diseases. Yet, postmenopausal women are consistently underrepresented in clinical trials exploring exercise interventions.
Based on emerging scientific evidence, the investigators hypothesize that morning exercise may lead to greater reductions in hepatic fat and improvements in cardiometabolic health compared to evening exercise in postmenopausal women with MASLD. Furthermore, the investigators propose that these effects may be partially mediated by exercise-induced changes in gut microbiota composition and function.
Thus, the main objective of the project is to investigate whether the timing of exercise modulates hepatic fat reduction, cardiometabolic adaptation, and gut microbiota remodeling in postmenopausal women with MASLD. To achieve this, the project will implement a randomized controlled trial in which 63 sedentary postmenopausal women diagnosed with MASLD will be randomly allocated into one of three groups: (i) morning exercise (07:00h), (ii) evening exercise (19:00h), or (iii) a usual-care control group receiving lifestyle recommendations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 45-75 years, postmenopausal for at least two years (stage +1a)
- •Body Mass Index (BMI) > 25 and < 40 kg/m²
- •Diagnosed hepatic steatosis (via ultrasound hyperechogenicity, FibroScan CAP score >280, or histological confirmation)
- •Sedentary lifestyle (no regular structured exercise)
- •Willingness to be randomized and adhere to study procedures, including all assessments and visits
- •Sufficient Spanish proficiency to understand and follow study instructions
- •Consent to store biological samples for future research
- •Participants should have a healthy circadian rhythm
排除标准
- •Contraindications for MRI (e.g., claustrophobia, pacemaker, metal implants)
- •History of major cardiovascular, endocrine, neurological, or kidney disease, or any clinical abnormalities (to be judged by the study physician)
- •First-degree family history of sudden cardiac death
- •Alcohol or substance abuse
- •Psychiatric, psychotic, eating, or sleep disorders (to be judged by the study physician)
- •Prior bariatric surgery, diagnosed HIV/AIDS, or inflammatory/autoimmune diseases
- •Cancer or any medical condition where exercise is contraindicated (to be judged by the study physician)
- •Recent or unstable metabolic conditions (e.g., diabetes, recent medication changes, or use of drugs affecting metabolism)
- •Recent (<3 months) use of antibiotics, statins, glucocorticoids, hormonal therapies, amiodarone, or myelosuppressive agents
- •Participation in weight-loss programs or special diets (e.g., ketogenic, high-carb)
- •Shift workers or caregivers with frequent nocturnal disruptions
研究组 & 干预措施
Usual-Care Control Group
干预措施: Usual-care control group (Behavioral)
Morning Exercise Group
干预措施: Morning exercise group (Behavioral)
Evening Exercise Group
干预措施: Evening exercise group (Behavioral)
结局指标
主要结局
Hepatic fat content
时间窗: Change from baseline in the mean adipose tissue content at 12 weeks
Hepatic fat content will be quantified using MRI
次要结局
- Pittsburgh Sleep Quality Index Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Perceived Stress Scale Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Depression, Anxiety, and Stress Scale Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Beck Depression Inventory Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Profile of Mood States Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Visceral adipose tissue(Change from baseline in the mean adipose tissue content at 12 weeks)
- Intra-muscular adipose tissue(Change from baseline in the mean adipose tissue content at 12 weeks)
- Body composition(Change from baseline in the whole-body composition at 12 weeks)
- Bone related parameters(Change from baseline in the whole-body mineral density and content at 12 weeks)
- Resting blood pressure(Change from baseline in the resting blood pressure related parameters at 12 weeks)
- Glucose metabolism(Change from baseline in the glucose related parameters at 12 weeks)
- Energy metabolism(Change from baseline in the energy metabolism related parameters at 12 weeks)
- Exercise performance(Change from baseline in the exercise performance related parameters at 12 weeks)
- Heart rate and heart rate variability(Change from baseline in the heart rate and heart rate variability related parameters at 12 weeks)
- Body weight(Change from baseline in the body weight at 12 weeks)
- Height(Change from baseline in the height at 12 weeks)
- Body mass index(Change from baseline in the height at 12 weeks)
- Fasting glucose levels(Change from baseline in the fasting glucose levels at 12 weeks)
- Fasting insulin levels(Change from baseline in the fasting insulin levels at 12 weeks)
- Fasting HbA1c levels(Change from baseline in the fasting HbA1c levels at 12 weeks)
- Fasting cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels(Change from baseline in the fasting cholesterol, HDL, and LDL levels at 12 weeks)
- International Physical Activity Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Morningness-Eveningness Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
- Three-Factor Eating Questionnaire(Change from baseline in the questionnaire score at 12 weeks)
研究者
Juan Manuel Alcantara Alcantara
Investigador Ramón y Cajal
Universidad de Almeria