Nonalcoholic Fatty Liver Disease - Intermittent Calorie Restriction (FLICR) Study
- Conditions
- Nonalcoholic SteatohepatitisNonalcoholic Fatty Liver
- Interventions
- Behavioral: Standard of careBehavioral: Intermittent calorie restriction
- Registration Number
- NCT05309642
- Lead Sponsor
- Ewha Womans University Mokdong Hospital
- Brief Summary
Several diets have been proposed to reduce liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD), and various effects on liver steatosis have been observed. The objective of this trial is to compare the effects of intermittent calorie restriction (ICR) (5:2 diet) and standard-of-care (SoC) on reduction of hepatic steatosis.
- Detailed Description
This is an open-label randomised controlled trial of patients with NAFLD. Patients are recruited in the Liver Outpatient Clinic of the Ewha Womans University Mokdong Hospital. The department of Nutritional Science and Food Management, Ewha Womans University will collaborate for this study.
About 72 patients (36 patients with body mass index \[BMI\] ≥25 kg/m2 and 36 patients with BMI \<25 kg/m2) will be enrolled in a 1:1 ratio to 12 weeks treatment with either 5:2 diet (ICR group, 18 patients in each BMI group), or general lifestyle advice from a hepatologist (standard of care; SoC group, 18 patients in each BMI group).
Beginning in week 3 (Visit 2), an ICR group and a SoC group are generated through randomisation. Both arms will be accompanied for a duration of 12 weeks. After 12 weeks from the completion of the experimental phase (wash-out period), there will be the "end of follow up" visit.
The whole duration of the study is 26 weeks (2 weeks lead-in, 12 weeks intervention and 12 weeks post-intervention investigation).
Magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) and MR-Elastography are conducted at the screening visit and at weeks 12.
There will be 5 visits at the study center (screening, randomization, week 8, end of treatment and end of study) and 10 phone visits (week 4, 5, 6, 7, 8, 10, 11, 12, 13, 14). At each visit clinical events, anthropometric index and standard laboratory parameters will be collected. Participants will fill in questionnaires capturing quality of life.
Adverse events will be recorded. Phone visits are used to survey the safety of patients.
Non-adherence to ICR for 20% of the total study period has been selected as cut off to define treatment failure at per-protocol analysis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 72
- NAFLD diagnosed by (1) Histologic assessment with a fat accumulation of more than 5% of the liver's weight in a biopsy, or (2) Radiologic assessment with a MRI-PDFF ≥8%.
- Age between 19 and 75 years
- Capability to understand the study and the individual consequences of participation
- Signed and dated declaration of agreement in the forefront of the study
- Daily alcohol consumption >30 g in men and >20 g in women
- Other causes of chronic liver disease (HBV, HCV, HDV, HEV, HIV), autoimmune diseases or chronic cholestatic liver disease, drug induced liver injury, hereditary haemochromatosis, Wilson disease, α-1-Antitrypsin deficiency
- Liver cirrhosis
- Hepatocellular carcinoma
- Medications which cause liver disease or secondary NAFLD (e.g. Tamoxifen, systemic Corticosteroids, Methotrexate, Tetracycline, Estrogens, Valproic acid)
- Changes in body weight > 5% in the last 3 months
- Intake of medical treatment for NAFLD/NASH in the last 6 months (except for vitamin E)
- Diabetes
- Pregnancy
- Patients after organ transplantations
- Missing or lacking consent capability
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Soc Arm Standard of care The SoC group will receive 80% of standard calorie (1,200-1,500 kcal/day or reducing 500-1000 kcal/day from standard calorie). ICR Arm Intermittent calorie restriction On 2 non-consecutive days per week, participants in the ICR (5:2 diet) group will be instructed to consume 500 kcal/day for women and 600 kcal/day for men.
- Primary Outcome Measures
Name Time Method Impact of ICR on liver steatosis by MRI-PDFF Baseline, 12 weeks The primary outcome of interest is a change in MRI-PDFF value of a least 30% with ICR
- Secondary Outcome Measures
Name Time Method Changes in visceral adipose tissue (VAT) Baseline, 12, and 24 weeks Measure the change of VAT with fat CT
Genetic analysis Baseline Polymorphism of PNPLA3, TM6SF2, TM4SF5, SREBF2, MBOAT7-TMC4, HSD17B13 and adenine insertion (A-INS) will be analyzed by NGS (Next Generation Sequencing)
Changes in anthropometrics Baseline, 12, and 24 weeks BMI (kg/m2)
Changes in gut microbiota Baseline, 12 weeks Evaluation of 16S rRNA gene sequencing
Changes in liver fibrosis by MR-Elastography Baseline, 12 weeks Measure the change of liver fibrosis with MR-Elastography
Changes in body composition analysis (BCA) Baseline, 12, and 24 weeks Measure the change of BCA with Inbody
Changes in hormone Baseline, 12 weeks Measure the change of leptin, adiponectin, ghrelin, GLP-1, apelin, and osteopontin
Changes in liver metabolite Baseline, 12 weeks Measure the change of diglycerides (DG), FA, phosphatidylethanolamines (PE), phosphatidylcholines (PC), methionine, SAMe, and methylthioadenosine
Changes in quality of life score Baseline, 12, and 24 weeks Measure the change of Quality of Life score with Chronic Liver Disease-NAFLD questionnaire (CLDQ). The CLDQ uses 29 items in four domains, each scored on a Likert scale from 1 (all of the time) to 7 (none of the time) representing the frequency of clinical symptoms and emotional problems in the last two weeks. Results are reported in the six subscale scores (abdominal symptoms, fatigue, systemic symptoms, activity, emotional functioning, worry) and a CLDQ overall score.
Trial Locations
- Locations (1)
Ewha Womans University College of Medicine
🇰🇷Seoul, Yangcheon-gu, Korea, Republic of