Prevention of NAFLD and CVD Through Lifestyle Intervention

Study Overview
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Brief Summary
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Prevention of non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) through lifestyle intervention (MAUCO+) is a clinical trial that aims to improve sarcopenia, aerobic capacity, body composition, and lipid profile, insulin resistance, cardiovascular risk, NAFLD, and maintain a healthier lifestyle. Through the implementation of physical activity and nutritional programs.

Detailed Description
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BACKGROUND. Gallstone disease (GSD), including gallstones and cholecystectomy, is a common digestive disease worldwide, and Chile has one of the highest reported rates of gallstone prevalence. GSD, in particular cholecystectomy, has been associated with nonalcoholic fatty liver disease (NAFLD). In previous studies, investigators confirmed the association of cholecystectomy with a higher risk of NAFLD only in men. Additionally, reasearchers found a higher cardiovascular event risk in 3 years for male gallstone carriers. Investigators aim to step forward toward translational research by evaluating the effectiveness of a risk-reduction strategy customized to our population. STUDY GOALS. To evaluate a metabolic risk reduction strategy based on: 1. A Physical exercise trial to increase muscle mass and strength, and 2. A nutritional intervention based on an anti-inflammatory diet, sleep hygiene, and prolonged fasting periods. METHODS. Intensive Lifestyle Intervention, Randomized Controlled Trial: 300 participants will be randomly allocated to control (n=150) or an experimental group (n=150). The control group will receive standard prevention recommendations, personalized advice, educational material regarding lifestyle and metabolic diseases, and follow-up evaluation of physical activity, physical condition, anthropometry, diet, and sleep habits. The intervention group will receive, tailored to each participant: 3.1 An Exercise Program consisting of directly supervised and home-based telehealth sessions emphasizing muscle building, and 3.2. A Nutritional plus Program based on a diet rich in anti-inflammatory components and legumes, low in fat and refined carbohydrates, controlled energy according to BMI, extended nocturnal fasting periods, and healthy sleep habits. The programs will have a 6-month intensive phase of bi-weekly directly supervised exercise sessions in a municipality gym and a weekly telehealth session, followed by six months of telephone support and bi-monthly direct supervision to reinforce adherence and early identification of risk factors for abandonment. Intervention outcomes measured at baseline and years 1 and 2 are changes in non-invasive serum and ultrasound-based biomarkers of NAFLD; improvement in sarcopenia, aerobic capacity, body composition, lipid profile, insulin resistance, and cardiovascular risk; among overweight participants, permanent loss of at least 5% body weight; the decrease of depression symptoms, improvement of quality of life scores, and maintenance of a healthier lifestyle. EXPECTED RESULTS: is expected that a 12-month intervention of a personalized physical activity program together with a metabolic protective diet will improve markers of metabolic syndrome and NAFLD and decrease CVD risk scores in all participants who adhere to more than 50% of both interventions, with a clear dose-response effect.

Official Title
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Cardiovascular Diseases (CVD) and Nonalcoholic Fatty Liver Diseases (NAFLD) Among Gallstone and Cholecystectomy Patients and the Impact of a Novel Diet and Muscle Training Program

Conditions
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Non-Alcoholic Fatty Liver Disease, Gallstone Disease

Intervention / Treatment
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* Other: Physical exercise and dietary intervention for NAFLD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With and without gallstones disease With various degrees of NAFLD (none too severe) Exclusion Criteria: Any significant comorbidity or physical limitation to undergo resistance exercise program Use of medications that alter muscle mass (e.g., corticosteroids) History of hepatitis B or C Use of hepatotoxic drugs

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physical exercise and dietary intervention for NAFLD<br>The exercise program will consist of muscular strength and aerobic exercises; additionally, each session will start and end with low intensity warm-up and cool down periods. The program will be divided in months. Months 1-2, twice a week directly-supervised exercises group sessions, and 1 telehealth session. Months 3-6, once a week directly-supervised group session and twice a week home-based telehealth. Months 7-12, Monthly telephone support. Months 12, 24 and 36, All participants (control and intervention arms) will receive a full evaluation. In the dietary intervention, investigators proposed a diet rich in anti-inflammatory components, legumes and in dietary fiber. The baseline evaluation of nutritional condition includes: anthropometry, bioimpedance analysis, hepatobiliary ultrasound, Fibroscan,blood lipids, and a battery of metabolic markers and a diet survey, Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24). Both interventions are performed in parallel. | Other: Physical exercise and dietary intervention for NAFLD<br>* Investigators will assess the efficiency of the intervention by measuring adherence to physical exercise and nutritional diet.<br>|
| No Intervention: Standard of care<br>Participants in the control arm first have a baseline evaluation of the nutritional condition, with anthropometry evaluation, bioimpedance analysis, hepatobiliary ultrasound, Fibroscan, blood lipids, a battery of metabolic markers, and a diet survey, Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24). After the evaluation period, participants received one counseling session, including written material, with advice to follow a healthy diet rich in fruits and vegetables, whole-grain foods, low in salt and sugars, and recommendations for an exercise plan of at least 30 minutes of aerobic exercise three times a week. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence and severity of Non-Alcoholic Fatty liver Disease (NAFLD) at baseline and 12 month later. | It will be measured through the liver steatosis marker Controlled Attenuation Parameter (CAP) (dB/m). | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Framingham Cardiovascular risk score | It will be measured at baseline and 12 months. | 36 months | 
| HDL cholesterol (mg/dL) | It will be measured at baseline and 12 months. | 36 months | 
| Triglycerides (mg/dL) | It will be measured at baseline and 12 months. | 36 months | 
| Glycemia (mg/dL) | It will be measured at baseline and 12 months. | 36 months | 
| Insulin (uU/mL) | It will be measured at baseline and 12 months. | 36 months | 
| HBA1c | It will be measured at baseline and 12 months. | 36 months | 
| usPCR (mg/L) | It will be measured at baseline and 12 months. | 36 months | 
| AST:ALT ratio | It will be measured at baseline and 12 months. | 36 months | 
| Total cholesterol (mg/dL) | It will be measured at baseline and 12 months. | 36 months | 
| Platelets (#cells/uL) | It will be measured at baseline and 12 months. | 36 months | 
| HOMA-IR | It will be measured at baseline and 12 months. | 36 months | 
| Total Bilirrubin (mg/dL) | It will be measured at baseline and 12 months. | 36 months | 
| Alkaline phosphatase (UI/l) | It will be measured at baseline and 12 months. | 36 months | 
| Glutamiz oxaloacetic transaminase (GOT) (UI/l) | It will be measured at baseline and 12 months. | 36 months | 
| Glutamic pyruvic trasaminase (GPT) (UI/l) | It will be measured at baseline and 12 months. | 36 months | 
| Gamma-glutamyl Transferase (GGT) (UI/l) | It will be measured at baseline and 12 months. | 36 months | 
| Metabolic syndrome | To be diagnosed with metabolic syndrome it is necessary to meet 3 or more conditions. (abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure and high fasting glucose). Metabolic syndrome will be measure at baseline and 12 month. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-inflammatory diet, Lifestyle modification, Physical Activity