Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis
Conditions
Keywords
Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis, MRI-PDFF, MR-Elastography, Intermittent Calorie Restriction, Liver metabolite, Gut microbiome
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.
Interventions
BEHAVIORALIntermittent calorie restriction
Recipes will be provided with suggestions of meals that would not exceed the calorie restriction. For the remaining 5 days of the week, they will receive instructions and recipes that follows the Korean Dietary Reference Intakes (KDRIs), with an intake limit of 2,000 kcal/day for women and 2,500 kcal/day for men. The percentage of energy (E%) from different macronutrients in the recipes will be 45-60 E% carbohydrates, 25 E% fat and 10-20 E% protein.
BEHAVIORALStandard of care
They will receive individualized guidance from a hepatologist on how to choose a healthy diet, to reduce the intake of sweets and saturated fatty acids, increase sources of unsaturated fat, avoid large portions, and to regularly eat 3 meals per day. Each participant will be provided a written summary of the dietary advice.
Sponsors
Ewha Womans University Mokdong Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomly allocated two groups; ICR (intermittent calorie restriction) group and SoC (standard-of-care) group
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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%. 2. Age between 19 and 75 years 3. Capability to understand the study and the individual consequences of participation 4. Signed and dated declaration of agreement in the forefront of the study
Exclusion criteria
1. Daily alcohol consumption \>30 g in men and \>20 g in women 2. 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 3. Liver cirrhosis 4. Hepatocellular carcinoma 5. Medications which cause liver disease or secondary NAFLD (e.g. Tamoxifen, systemic Corticosteroids, Methotrexate, Tetracycline, Estrogens, Valproic acid) 6. Changes in body weight \> 5% in the last 3 months 7. Intake of medical treatment for NAFLD/NASH in the last 6 months (except for vitamin E) 8. Diabetes 9. Pregnancy 10. Patients after organ transplantations 11. Missing or lacking consent capability
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in liver metabolite | Baseline, 12 weeks | Measure the change of diglycerides (DG), FA, phosphatidylethanolamines (PE), phosphatidylcholines (PC), methionine, SAMe, and methylthioadenosine |
| 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 anthropometrics | Baseline, 12, and 24 weeks | BMI (kg/m2) |
| Changes in hormone | Baseline, 12 weeks | Measure the change of leptin, adiponectin, ghrelin, GLP-1, apelin, and osteopontin |
| Changes in visceral adipose tissue (VAT) | Baseline, 12, and 24 weeks | Measure the change of VAT with fat CT |
| 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. |
| 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 body composition analysis (BCA) | Baseline, 12, and 24 weeks | Measure the change of BCA with Inbody |
Countries
South Korea
Outcome results
None listed