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

NCT05309642 | Completed

• 1 other identifier: FLICR
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Nonalcoholic Fatty Liver; Nonalcoholic Steatohepatitis

Keywords

Nonalcoholic Fatty Liver; Nonalcoholic Steatohepatitis; MRI-PDFF; MR-Elastography; Intermittent Calorie Restriction; Liver metabolite; Gut microbiome

Outcome Measures

Primary Outcomes (1)

• Impact of ICR on liver steatosis by MRI-PDFF

  The primary outcome of interest is a change in MRI-PDFF value of a least 30% with ICR

  Baseline, 12 weeks

Secondary Outcomes (9)

• Changes in liver fibrosis by MR-Elastography

  Baseline, 12 weeks

• Changes in anthropometrics

  Baseline, 12, and 24 weeks

• Changes in body composition analysis (BCA)

  Baseline, 12, and 24 weeks

• Changes in visceral adipose tissue (VAT)

  Baseline, 12, and 24 weeks

• Changes in quality of life score

  Baseline, 12, and 24 weeks

Study Arms (2)

ICR Arm

ACTIVE COMPARATOR

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.

Behavioral: Intermittent calorie restriction

Soc Arm

PLACEBO COMPARATOR

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

Behavioral: Standard of care

Interventions

Intermittent calorie restriction 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.

ICR Arm

Standard of care 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.

Soc Arm

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ewha Womans University Mokdong Hospital: lead

Study Sites (1)

Ewha Womans University College of Medicine

Seoul, Yangcheon-gu, 07985, South Korea

Location

Related Publications (10)

• 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.

  PMID: 33898960 BACKGROUND

• 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.

  PMID: 33307021 BACKGROUND

• 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.

  PMID: 30475957 BACKGROUND

• 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.

  PMID: 30408717 BACKGROUND

• 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.

  PMID: 30142427 BACKGROUND

• 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.

  PMID: 31852444 BACKGROUND

• 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.

  PMID: 23171320 BACKGROUND

• 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.

  PMID: 30646030 BACKGROUND

• 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.

  PMID: 39181426 DERIVED

• 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.

  PMID: 37533096 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Hwi Young Kim, Professor

  Ewha Womans University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomly allocated two groups; ICR (intermittent calorie restriction) group and SoC (standard-of-care) group

Study Record Dates

• First Submitted: March 12, 2022
• First Posted: April 4, 2022
• Study Start: March 7, 2022
• Primary Completion: December 6, 2023
• Study Completion: December 6, 2023
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)