Effects of Time-restricted Hypocaloric Diet in Patients With NAFLD

Study Overview
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Brief Summary
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The effects of a time-restricted hypocaloric Mediterranean type diet compared to a conventional hypocaloric Mediterranean type diet on blood glucose metabolism and liver steatosis in people with non-alcoholic fatty liver disease will be investigated.

Detailed Description
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The goal of this clinical trial is to evaluate the effects of the time in which food intake is restricted (morning or evening hours or no restriction in time) on glucose metabolism and liver steatosis in the context of a hypocaloric diet plan in 54 patients with non-alcoholic fatty liver disease (NAFLD). The participants will be divided into 3 groups of 18 individuals each and will be randomly assigned to one of the 3 dietary interventions. In the first group (control group), participants will be given a weight loss program based on the principles of the Mediterranean Diet (energy deficit of 500 kcal/day with the aim of losing 0.5 kg per week) with the instruction to consume their meals throughout the day, without time restriction. In the second group (early eaters), individuals will be given a weight loss program based on the principles of the Mediterranean Diet (energy deficit of 500 kcal/day with the aim of losing 0.5 kg per week), and they will be asked to consume all of their meals within 10 hours (between 07:00-09:00 and 17:00-19:00) and refrain from consuming caloric foods and drinks for the remaining 14 hours. In the third group (late eaters), individuals will be given a weight loss program based on the principles of the Mediterranean Diet (energy deficit of 500 kcal/day with the aim of losing 0.5 kg per week), and they will be asked to consume all of their meals within 10 hours (between 11:00-13:00 and 21:00-23:00) and refrain from consuming caloric foods and drinks for the remaining 14 hours. Finally, all groups will be instructed to moderately exercise for 150 minutes per week.

Official Title
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Effects of a Time-restricted Hypocaloric Mediterranean Diet in Patients With Non-alcoholic Fatty Liver Disease on Glucose Metabolism (CHRONO-NAFLD Project)

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: Early Time-Restricted Feeding Plus Hypocaloric Mediterranean Diet
* Other: Late Time-Restricted Feeding Plus Hypocaloric Mediterranean Diet
* Other: Hypocaloric Mediterranean Diet Without Time Restriction In Feeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index >25 kg/m2 Liver steatosis with Magnetic Resonance Elastography (MRE) Exclusion Criteria: Other chronic liver diseases Alcohol consumption >20 g/day (female) and >30 g/day (male) Medications that cause liver disease or secondary NAFLD (e.g. tamoxifen, corticosteroids, Methotrexate, tetracycline, estrogens, valproic acid) Changes in body weight ± 3 % in the last 3 months Patients following a hypocaloric diet program and/or time-restricted feeding and/or other intermittent fasting protocols Unstable glucose-lowering medications in the last 6 months Body weight lowering medications and/or history of bariatric surgery Statins and/ or other fat-reducing medications if not taken in steady dosage for at least 3 months Uncontrolled type 2 diabetes mellitus defined as HbA1c value > 9.0% or insulin depending type 1 and 2 diabetes mellitus Pregnancy Lactation Immunologic or inflammatory diseases Depression and other psychiatric diseases Patients working in shifts Cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Time-Restricted Feeding Plus Hypocaloric Mediterranean Diet<br>Early 14:10 time-restricted feeding plus hypocaloric Mediterranean diet | Other: Early Time-Restricted Feeding Plus Hypocaloric Mediterranean Diet<br>* 18 patients with NAFLD will be asked to follow an early 14:10 (14 hours fasting and 10 hours feeding) time-restricted (eating between 08:00-18:00) and individualized Mediterranean diet plan with caloric restriction (energy deficit of 500 kcal/day) for 12 weeks<br>|
| Experimental: Late Time-Restricted Feeding Plus Hypocaloric Mediterranean Diet<br>Late 14:10 time-restricted feeding plus hypocaloric Mediterranean diet | Other: Late Time-Restricted Feeding Plus Hypocaloric Mediterranean Diet<br>* 18 patients with NAFLD will be asked to follow a late 14:10 (14 hours fasting and 10 hours feeding) time-restricted (eating between 12:00-22:00) and individualized Mediterranean diet plan with caloric restriction (energy deficit of 500 kcal/day) for 12 weeks<br>|
| Active Comparator: Hypocaloric Mediterranean Diet Without Time Restriction In Feeding<br>Hypocaloric Mediterranean diet without time restriction in feeding | Other: Hypocaloric Mediterranean Diet Without Time Restriction In Feeding<br>* 18 patients with NAFLD will be asked to follow an individualized Mediterranean diet plan with caloric restriction (energy deficit of 500 kcal/day) without time restriction in feeding (eating throughout the day) for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood glucose concentrations | Clinically significant change in blood glucose concentrations (mg/dL) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Clinically significant change in body weight (kg) | 12 weeks | 
| Change in blood insulin concentrations | Clinically significant change in blood insulin concentrations (μU/L) | 12 weeks | 
| Change in Controlled Attenuation Parameter (CAP) | Clinically significant change in CAP (dB/m) | 12 weeks | 
| Change in blood lipids levels | Clinically significant change in triglycerides (mg/dL), total cholesterol (mg/dL), low-density lipoprotein (mg/dL) and high-density lipoprotein (mg/dl) | 12 weeks | 
| Change in Chronic Liver Disease Questionnaire (CLDQ) | Clinically significant change in health status within individuals with NAFLD. The CLDQ includes 29 items in the following domains: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. Overall CLDQ scores calculated for each domain range from 1 (most impaired) to 7 (minimum frequency of symptoms). The total score is calculated as the average score of the 29 items. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Time-Restricted Feeding, Mediterranean Diet