Nonalcoholic Fatty Liver Disease - Intermittent Calorie Restriction (FLICR) Study

NCT ID: NCT05309642

Last Updated: 2024-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-07

Study Completion Date

2023-12-06

Brief Summary

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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

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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.

Conditions

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Nonalcoholic Fatty Liver Nonalcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomly allocated two groups; ICR (intermittent calorie restriction) group and SoC (standard-of-care) group
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ICR Arm

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.

Group Type ACTIVE_COMPARATOR

Intermittent calorie restriction

Intervention Type BEHAVIORAL

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.

Soc Arm

The SoC group will receive 80% of standard calorie (1,200-1,500 kcal/day or reducing 500-1000 kcal/day from standard calorie).

Group Type PLACEBO_COMPARATOR

Standard of care

Intervention Type BEHAVIORAL

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.

Interventions

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Intermittent 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.

Intervention Type BEHAVIORAL

Standard 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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ewha Womans University Mokdong Hospital

OTHER

Sponsor Role lead

Responsible Party

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Hwi Young Kim

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hwi Young Kim, Professor

Role: PRINCIPAL_INVESTIGATOR

Ewha Womans University College of Medicine

Locations

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Ewha Womans University College of Medicine

Seoul, Yangcheon-gu, South Korea

Site Status

Countries

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South Korea

References

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Holmer M, Lindqvist C, Petersson S, Moshtaghi-Svensson J, Tillander V, Brismar TB, Hagstrom H, Stal P. Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial. JHEP Rep. 2021 Feb 17;3(3):100256. doi: 10.1016/j.jhepr.2021.100256. eCollection 2021 Jun.

Reference Type BACKGROUND
PMID: 33898960 (View on PubMed)

Younossi ZM, Corey KE, Lim JK. AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology. 2021 Feb;160(3):912-918. doi: 10.1053/j.gastro.2020.11.051. Epub 2020 Dec 9.

Reference Type BACKGROUND
PMID: 33307021 (View on PubMed)

Schubel R, Nattenmuller J, Sookthai D, Nonnenmacher T, Graf ME, Riedl L, Schlett CL, von Stackelberg O, Johnson T, Nabers D, Kirsten R, Kratz M, Kauczor HU, Ulrich CM, Kaaks R, Kuhn T. Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial. Am J Clin Nutr. 2018 Nov 1;108(5):933-945. doi: 10.1093/ajcn/nqy196.

Reference Type BACKGROUND
PMID: 30475957 (View on PubMed)

Retterstol K, Svendsen M, Narverud I, Holven KB. Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: A randomized controlled study. Atherosclerosis. 2018 Dec;279:52-61. doi: 10.1016/j.atherosclerosis.2018.10.013. Epub 2018 Oct 17.

Reference Type BACKGROUND
PMID: 30408717 (View on PubMed)

Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, Chim AM, Chan CK, Leung JK, Chu WC, Woo J, Chan HL. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol. 2018 Dec;69(6):1349-1356. doi: 10.1016/j.jhep.2018.08.011. Epub 2018 Aug 22.

Reference Type BACKGROUND
PMID: 30142427 (View on PubMed)

Cai H, Qin YL, Shi ZY, Chen JH, Zeng MJ, Zhou W, Chen RQ, Chen ZY. Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial. BMC Gastroenterol. 2019 Dec 18;19(1):219. doi: 10.1186/s12876-019-1132-8.

Reference Type BACKGROUND
PMID: 31852444 (View on PubMed)

Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012 Nov 21;11:98. doi: 10.1186/1475-2891-11-98.

Reference Type BACKGROUND
PMID: 23171320 (View on PubMed)

Carter S, Clifton PM, Keogh JB. Effect of Intermittent Compared With Continuous Energy Restricted Diet on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Noninferiority Trial. JAMA Netw Open. 2018 Jul 6;1(3):e180756. doi: 10.1001/jamanetworkopen.2018.0756.

Reference Type BACKGROUND
PMID: 30646030 (View on PubMed)

Lee HA, Moon H, Kim Y, Lee JK, Lee HA, Kim HY. Effects of Intermittent Calorie Restriction in Nondiabetic Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease. Clin Gastroenterol Hepatol. 2025 Jan;23(1):114-123.e13. doi: 10.1016/j.cgh.2024.06.051. Epub 2024 Aug 23.

Reference Type DERIVED
PMID: 39181426 (View on PubMed)

Lee HA, Moon H, Kim Y, Lee HA, Kim HY. Effect of 12-week intermittent calorie restriction compared to standard of care in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Trials. 2023 Aug 2;24(1):490. doi: 10.1186/s13063-023-07444-4.

Reference Type DERIVED
PMID: 37533096 (View on PubMed)

Other Identifiers

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FLICR

Identifier Type: -

Identifier Source: org_study_id

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