Effects of Time-restricted Eating Supported by Mobile Technology in Patients With Non-alcoholic Fatty Liver Disease: Randomized Controlled Trial

Study Overview
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Brief Summary
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In non-alcoholic fatty liver disease (NAFLD), it is established that calorie restriction is the most essential dietary modification. The time-restricted diet is successful lowering total calorie consumption and insulin resistance, and is anticipated to be beneficial for patients with NAFLD. Therefore, this study aims to conduct a prospective study to determine the effect of time-restricted diet via a mobile application on the amount of intrahepatic fat and 10-year cardiovascular disease risk in patients with NAFLD.

Official Title
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Effects of Time-restricted Eating Supported by Mobile Technology in Patients With Non-alcoholic Fatty Liver Disease: Randomized Controlled Trial

Conditions
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Non-Alcoholic Fatty Liver Disease, Time Restricted Feeding, Mobile Technology

Intervention / Treatment
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* Behavioral: Mobile application and wearable device
* Behavioral: Time-restricted eating


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 19 years who are willing and able to complete all procedures Hepatic steatosis by imaging (ultrasound, computed tomography, magnetic resonance imaging, and controlled attenuation parameter (≥260 dB/m)) Exclusion Criteria: Body mass index (BMI) <23 Other causes of chronic liver disease (HBV, HCV), autoimmune diseases or chronic cholestatic liver disease Medications which cause liver disease or secondary hepatic steatosis (Tamoxifen, systemic corticosteroids, methotrexate, tetracycline, estrogens, valproic acid, and statin (registration is possible if statin is delivered in a consistent dosage within 12 weeks) Significant alcohol intake (>210g/week for men, >140g/week for women) Severe medical comorbidities (ischemic heart disease, 3rd degree atrioventricular block, chronic obstructive pulmonary disease, severe hypertension (blood pressure > 200/120 mmHg) Psychiatric illnesses which limit ability to exercise safely Diagnosed with diabetes on medication or insulin Participation in a weight-loss program within 12 weeks MRI contraindications

Ages Eligible for Study
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Minimum Age: 19 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mobile application-supported both calorie restriction and time-restricted eating (mCR/TRE)<br>This arm receives wearable device and mobile application-supported nutritional counseling for four months. The nutritional counseling consists of both calorie restriction (500kcal below estimated energy requirement) and time-restricted eating (an 8-hour period (from 10 a.m. to 6 p.m.) each day). | Behavioral: Mobile application and wearable device<br>* Mobile application-supported nutritional counseling includes education, monitoring, interaction, and physical activity<br>Behavioral: Time-restricted eating<br>* Time-restricted eating (an 8-hour period (from 10 a.m. to 6 p.m.) each day)<br>|
| Active Comparator: Mobile application-supported calorie restriction (mCR)<br>This arm receives wearable device and mobile application-supported nutritional counseling for four months. The nutritional counseling consists of only calorie restriction (500kcal below estimated energy requirement). | Behavioral: Mobile application and wearable device<br>* Mobile application-supported nutritional counseling includes education, monitoring, interaction, and physical activity<br>|
| No Intervention: Calorie restriction (CR)<br>Standard of care. This arm receives a brief counseling of calorie restriction. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hepatic steatosis (%) | Change in hepatic steatosis (%) on Magnetic Resonance Imaging (MRI) Proton Density Fat fraction (PDFF) of the Liver | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 10-year atherosclerotic cardiovascular disease (ASCVD) risk | Evaluate the mean change in atherosclerotic cardiovascular disease (ASCVD) risk score (%) (high ASCVD risk score means high risk of ASCVD) | 16 weeks | 
| Change in liver fibrosis (kPa) by Magnetic Resonance Elastography (MRE) | Evaluate the mean change in liver fibrosis (kPa) on Magnetic Resonance Elastography (MRE) of the Liver | 16 weeks | 
| Change in body weight (kg) | Evaluate the mean change in body weight (kg) | 16 weeks | 
| Change in systolic blood pressure (mmHg) | Evaluate the mean change in systolic blood pressure (mmHg) | 16 weeks | 
| Change in low-density lipoprotein level (mg/dL) | Evaluate the mean change in low-density lipoprotein level (mg/dL) | 16 weeks | 
| Change in serum alanine aminotransferase level (IU/L) | Evaluate the mean change in serum alanine aminotransferase level (IU/L) | 16 weeks | 
| Change in hemoglobin A1c level (%) | Evaluate the mean change in hemoglobin A1c level (%) | 16 weeks | 
| Change in insulin sensitivity | Evaluate the mean change in homeostatic model assessment for insulin resistance (HOMA-IR) | 16 weeks | 
| Change in urine microalbumin (mcg/min) | Evaluate the mean change in urine microalbumin (mcg/min) | 16 weeks | 
| Change in body muscle mass (kg) | Evaluate the mean change in body muscle mass (kg) as measured by bioelectrical impedance analysis (InBody) | 16 weeks | 
| Change in liver fibrosis by liver stiffness (kPa) | Evaluate the mean change in liver fibrosis by liver stiffness (kPa) under FibroScan® | 16 weeks | 
| Change in liver steatosis by controlled attenuation parameter (dB/m) | Evaluate the mean change in liver steatosis by controlled attenuation parameter (dB/m) under FibroScan® | 16 weeks | 
| Change in body weight (kg) at 6 months after the intervention | Evaluate the mean change in body weight (kg) at 24 weeks after the end of 16-week intervention period | 40 weeks | 
| Change in body weight (kg) at 12 months after the intervention | Evaluate the mean change in body weight (kg) at 48 weeks after the end of 16-week intervention period | 64 weeks |