Efficacy of 12-week Daytime Restricted Eating on Hepatic Steatosis of Obesity

Official title

Efficacy of 12-week Daytime Restricted Eating on Hepatic Steatosis of Obesity: Randomized, Open-label, Parallel Group, Controlled Superiority Trial _ CHRONOSTEATOSIS

Overview

The objective of this study is to demonstrate that an \< or equal to 8-hour time-restricted eating (i.e., fasting for at least 16 hours every day), not focusing on reducing caloric intake, reduces intra-hepatic fat in patients with obesity and Metabolic dysfunction-Associated Steatotic liver Disease (MASLD).

Detailed description

Obesity is a growing health problem. The increase in obesity is driving the growing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD, formerly called non-alcoholic fatty liver disease or NAFLD).

Chronobiology has revealed new risk factors for metabolic disease including MASLD. Proof-of-concept studies showed that time-restricted eating (TRE), a dietary intervention that involves longer fasting periods (typically \> 12 h per day) without caloric restriction, reprograms metabolism favorably. The state of the art now justifies clinical trials on clinical populations.

The aim of this randomized, parallel group, controlled study is to test the efficacy of Time Restricted Eating (TRE) implemented with dietary coaching and a dedicated mobile application compared to usual care. The primary endpoint is the evolution of liver fat content quantified by Magnetic Resonance Imaging (MRI).

Patients presenting all inclusion criteria without non-inclusion ciriteria will be included and a Magnetic Resonnance Imaging of the liver will be programmed. Randomization will be performed within 3 months post inclusion after MRI results are obtained. Only patients showing Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) \> or equal to 8% will be randomized. Other patients will be withdrawn from study before randomization.

After randomization, both groups will benefit from the standard of care for obesity management and metabolic assessment. Both groups will benefit from dietary counselling to achieve a balanced diet (no calorie restriction) and increase physical activity as recommended. This counselling will be performed by weekly phone calls of a centralized dietetician during a period of 12 weeks. Both groups of patients will use a mobile application to daily register time of first food intake and of time of last food intake (through time-stamped photos of first and last feedings). This will allow to know length of the patient's eating period per 24 hours.

Difference between the 2 groups of patients is only that, in the experimental arm (TRE), patients will additionnaly be instructed to reduce time of daily food intake to a window of 8 hours per day or less and thus increase daily fasting to at least 16 hours. This coaching will be performed during the weekly phone calls of a centralized dietetician.

Interventions

• Behavioral Time Restricted Eating
  Coaching of the patient by a dietetician for reduction of time of daily food intake to a window of 8 hours per day or less and thus increase of daily fasting to at least 16 hours, in addition to usual dietary counselling to achieve a balanced diet (no calorie restriction) and increase physicial activity as recommended (current guidelines).
• Behavioral Usual care only
  Usual care: dietary counselling to achieve a balanced diet (no calorie restriction) and increase physicial activity as recommended (current guidelines).

Primary outcome measures

• Liver fat content quantified by Magnetic Resonance Imaging Proton Density Fat Fraction [Time frame: 12 weeks post randomization]

Secondary outcome measures (12)

• Average lenght of the eating period per 24 hours [Time frame: 12 weeks post randomization]
• Liver steatosis and Stiffness as assessed by the Fibroscan [Time frame: 12 weeks post randomization]
• Hepatic outcomes evaluated through aspartates aminotransferases (ASAT) blood level before randomization and at 12 weeks post randomization. [Time frame: 12 weeks post randomization]
• Physical activity level measured by accelerometry with a watch accelerometer [Time frame: 12 weeks post randomization]
• Anthropometric outcomes assessed by body weight. [Time frame: 12 weeks post randomization]
• Anthropometric outcomes assessed by impedancemetry [Time frame: 12 weeks pour randomization]
• Anthropometric outcomes assessed by Magnetic Resonance Imaging of the liver [Time frame: 12 weeks post randomization]
• Blood pressure [Time frame: 12 weeks post randomization]
• Metabolic outcomes related to energy balance evaluated through glycated hemoglobin (HbA1c) blood level before randomization and at 12 weeks post randomization. [Time frame: 12 weeks post randomization]
• Metabolic outcomes related to energy balance or insulin signaling/resistance assessed through indirect calorimetry [Time frame: 12 weeks post randomization]
• Depression assessed using the PHQ-9 questionnaire [Time frame: 12 weeks post randomization]
• Anxiety assessed using the GAD-7 questionnaire [Time frame: 12 weeks post randomization]

Eligibility criteria

Inclusion criteria

• Body mass index (BMI) between 30.0 and 49.9 kg/m2
• Age between 18 and 65 years (limits included)
• Sedentary (light-intensity physical activity less than 1 hour per week) or moderately active (moderate exercise 1 to 2 hours per week). Self-declared criteria.
• Weight stable for at least 3 months prior to the beginning of the study (gain or loss <4 kg). Self-declared criteria.
• Able to give written informed consent
• Self-reported eating interval > 12 hours per day
• Subject who owns a smartphone with access to the internet, and agrees to use it in the study
• Affiliation with French social security system or beneficiary from such system
• Fibroscan® Controlled Attenuation Parameter (CAP) > 300 dB/ms
• Hepatitis B and C serologies negative (or showing past-infection or protective immunization)

Exclusion criteria

• Alcohol intake > 20 g/day
• Night-shift workers or rotating shift workers
• Smoking
• Patient with diabetes if HbA1c not at target (<7%) and/or using a non-authorized medication)
• Chronic liver disease other than MASLD
• Severe hepatic disease (cirrhosis, hepatocellular carcinoma)
• Severe cardiac disease (Chronic heart failure classified as being in New York Heart Association (NYHA) Class III or IV)
• Severe Kidney disease with CKD-EPI<30 mL/min/1,73m2
• Initiation of hormonal treatment during the study period
• Medications affecting weight or energy balance
• Magnetic Resonance Imaging (MRI) not possible due to patient's anthropometric characteristics. Any of the following:

• abdominal and/or thoracic circumference with arms greater than 200 cm
• Sagittal diameter (or abdominal height, i.e. the distance between the dorsum and the apex of the abdomen, which was measured in the supine position at the midpoint between the iliac crest and the last rib) over 70 cm
• body weight over 160 kg
• MRI not possible due to the following (an MRI safety screening form will have to be filled for inclusion): presence of a pacemaker or cardiac defibrillator or cardiovascular catheter or neurostimulator or an implantable electronic pump for automated drug injection or an electronically-controlled implantable chamber. Ocular metallic foreign bodies
• History of severe eating disorders: Binge Eating Disorder, Bulimia Nervosa; Night eating syndrome
• Minors
• Adults under guardianship, trusteeship or under safeguard of justice
• Other clinical trial participation that could interfere with the study
• Pregnant women or women trying to be pregnant
• Nursing mothers
• Any treatment triggering hepatic steatosis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 9 centers

• CHU Angers — Angers
• CHU Bordeaux — Bordeaux
• CHU Dijon-Bourgogne — Dijon
• CHU Lyon — Lyon
• CHU Marseille — Marseille
• CHU Montpellier — Montpellier
• CHU Nantes — Nantes
• Hôpital Européen Georges Pompidou — Paris
• … and 1 more center

Identifiers

NCT: NCT07378072 · RC21_0569

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗