Effect of Intermittent Calorie Restriction on MASLD Patients With Abnormal Glucose Metabolism

NCT04283942 | Completed Results

• 1 other identifier: B2019-256R
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to observe the effect of 5:2 intermittent calorie restriction (fasting 2 days each week) on liver fat content in MASLD patients with abnormal blood glucose.

Conditions

Fatty Liver Disease; Type 2 Diabetes; Impaired Glucose Regulation

Keywords

Metabolic dysfunction-associated steatotic liver disease; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change of Liver Fat Content in %

  Change of liver fat content in %.

  From baseline to week 12

Secondary Outcomes (12)

• Change of Weight

  From baseline to week 12

• Change of Blood Glucose: Fasting Blood Glucose

  From baseline to week 12

• Change of Blood Glucose: 2h Postload Blood Glucose

  From baseline to week 12

• Change of HbA1c

  From baseline to week 12

• Change of Liver Enzymes: Alanine Aminotransferase

  From baseline to week 12

Other Outcomes (6)

• Change of Fat Mass

  From baseline to week 12

• Change of Lean Mass

  From baseline to week 12

• Change of Abdominal Adipose Tissue Area

  From baseline to week 12

Study Arms (2)

Intermittent Calorie Restriction (ICR)

EXPERIMENTAL

Participants in ICR group were instructed to ensure 2 successive days of fasting-mimicking and 5 days of recovery per week. On fasting-mimicking days, the participants were instructed to consume approximately 500 kcal/day and they were provided with plant-based meal replacement (ZhenBaiNian nutrition bar, Beijing Wanlaikang Nutrition and Health Food Science and Technology Research Institute Co., Ltd, China) to improve adherence and ensured adequate intake of micronutrients. In the rest 5 days of recovery per week, participants were allowed to consume their usual diet.

Behavioral: Intermittent calorie restriction (ICR)

Control (Continuous calorie restriction, CCR)

OTHER

Participants in control group were instructed to consume the prescribed calories (25 kcal / kg × \[height (cm) - 100\] kg) every day by eating conventional food without time restriction.

Behavioral: Continuous calorie restriction (CCR)

Interventions

Intermittent calorie restriction (ICR) BEHAVIORAL

Participants in ICR group were instructed to ensure 2 successive days of fasting-mimicking and 5 days of recovery per week. On fasting-mimicking days, the participants were instructed to consume approximately 500 kcal/day and they were provided with plant-based meal replacement to improve adherence and ensured adequate intake of micronutrients. In the rest 5 days of recovery per week, participants were allowed to consume their usual diet. Participants will receive dietary counseling from experienced nutritionists and eat a balanced diet (macronutrient distribution of approximately 10-15% protein, 55-65% carbohydrate and 20-30% fat).They are required to write daily dietary log. Besides, they are required to maintain their exercise routines and record their daily steps using a unified pedometer (Redmi Smart Band, Xiaomi Corporation, China). The use of drugs affecting blood glucose and LFC will be avoided.

Also known as: Intermittent fasting

Intermittent Calorie Restriction (ICR)

Continuous calorie restriction (CCR) BEHAVIORAL

Participants in CCR group were instructed to consume the prescribed calories (25 kcal / kg × \[height (cm) - 100\] kg) every day by eating conventional food without time restriction. Participants will receive dietary counseling from experienced nutritionists and eat a balanced diet (macronutrient distribution of approximately 10-15% protein, 55-65% carbohydrate and 20-30% fat).They are required to write daily dietary log. Besides, they are required to maintain their exercise routines and record their daily steps using a unified pedometer (Redmi Smart Band, Xiaomi Corporation, China). The use of drugs affecting blood glucose and LFC will be avoided.

Also known as: Daily calorie restriction

Control (Continuous calorie restriction, CCR)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70
• Diagnosed as fatty liver by ultrasound or magnetic resonance imaging
• BMI ≥ 24 kg/m2
• abnormal glucose metabolism: (meeting at least one):
• Impaired glucose regulation: fasting blood glucose ≥ 100 mg/dL, postprandial blood glucose ≥ 140 mg/dL or HbA1c ≥ 5.7%
• Diabetes mellitus: diabetic symptoms + plasma glucose concentration ≥ 200 mg/dL at any time or fasting plasma glucose concentration ≥ 100 mg/dL or OGTT 2 h plasma glucose concentration ≥ 200 mg/dL

You may not qualify if:

• Type 1 diabetes, gestational diabetes and other special types of diabetes
• Poor blood glucose control, HbA1c \> 8.5% within 3 months
• Taking antidiabetic drugs in the past month
• Serum ALT \> 6 times of normal upper limit
• Excessive alcohol consumption (alcohol intake: men \> 140 g, women \> 70 g in the past 6 months)
• Other liver diseases: such as acute and chronic viral hepatitis, drug-induced hepatitis, immune hepatitis, liver cirrhosis, liver cancer, etc
• Taking drugs that may affect MASLD in the past three months, such as vitamin E
• Biliary obstructive diseases
• Other diseases affecting glucose and lipid metabolism: hyperthyroidism, hypothyroidism, Cushing's syndrome, etc
• Chronic kidney disease (serum creatinine ≥ 2.0 mg/dL)
• Life expectancy of no more than 5 years
• Already pregnant or plan to be pregnant in the near future
• Mental illness
• Other conditions affecting follow-up
• Have participated in other clinical trials in the past 4 weeks

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, China

Location

Related Publications (17)

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  PMID: 26707365 BACKGROUND

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• Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014 Dec;60(6):2099-108. doi: 10.1002/hep.27406. Epub 2014 Oct 29.

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• Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002 Apr 18;346(16):1221-31. doi: 10.1056/NEJMra011775. No abstract available.

  PMID: 11961152 BACKGROUND

• Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F, Roverato A, Guaraldi G, Lonardo A. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016 May;31(5):936-44. doi: 10.1111/jgh.13264.

  PMID: 26667191 BACKGROUND

• Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, Tataranni PA. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes. 2002 Jun;51(6):1889-95. doi: 10.2337/diabetes.51.6.1889.

  PMID: 12031978 BACKGROUND

• Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology. 2014 Mar;59(3):1174-97. doi: 10.1002/hep.26717. Epub 2014 Jan 16.

  PMID: 24002776 BACKGROUND

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• Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, Emick D, Lok AS, Conjeevaram HS. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol. 2005 May;100(5):1072-81. doi: 10.1111/j.1572-0241.2005.41334.x.

  PMID: 15842581 BACKGROUND

• Sundfor TM, Svendsen M, Tonstad S. Intermittent calorie restriction-a more effective approach to weight loss? Am J Clin Nutr. 2018 Nov 1;108(5):909-910. doi: 10.1093/ajcn/nqy288. No abstract available.

  PMID: 30475966 BACKGROUND

• Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377):eaai8700. doi: 10.1126/scitranslmed.aai8700.

  PMID: 28202779 BACKGROUND

• Cheng CW, Villani V, Buono R, Wei M, Kumar S, Yilmaz OH, Cohen P, Sneddon JB, Perin L, Longo VD. Fasting-Mimicking Diet Promotes Ngn3-Driven beta-Cell Regeneration to Reverse Diabetes. Cell. 2017 Feb 23;168(5):775-788.e12. doi: 10.1016/j.cell.2017.01.040.

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• Johari MI, Yusoff K, Haron J, Nadarajan C, Ibrahim KN, Wong MS, Hafidz MIA, Chua BE, Hamid N, Arifin WN, Ma ZF, Lee YY. A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease. Sci Rep. 2019 Aug 2;9(1):11232. doi: 10.1038/s41598-019-47763-8.

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• 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.

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• Sun X, Li F, Yan H, Chang X, Yao X, Yang X, Wu S, Suo Y, Zhu X, Wang C, Gao J, Wang H, Chen Y, Xia M, Bian H, Gao X. Intermittent compared with continuous calorie restriction for treatment of metabolic dysfunction-associated steatotic liver disease: a randomized clinical trial. Am J Clin Nutr. 2025 Jan;121(1):158-166. doi: 10.1016/j.ajcnut.2024.10.012. Epub 2024 Oct 22.

  PMID: 39447676 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Hua Bian
• Organization: Zhongshan Hospital, Fudan University

zhongshan_bh@126.com

+86 64041990

Study Officials

• Hua Bian

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

• Xin Gao

  Shanghai Zhongshan Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Director

Model Details: Patients were randomly divided into intermittent calorie restriction group and control group for 12 weeks of intervention. Both groups will be followed up 4 weeks after intervention. ICR group: during the 2-day fasting-mimicking period each week, the food based on plant ingredients will be served (4 pieces of nutrition bars / day, 1:2:1 for breakfast, lunch and dinner, 124.4kcal/piece, 497.2kcal / day in total). In the rest 5 days each week, subjects are allowed ad libitum to their usual food. Control group: continuous calorie restriction (CCR). Under the guidance of nutritionist, subjects have to learn the method of food calories calculation. For each day, the daily calories intake is limited to 25 kcal / kg × standard weight \[kg, estimated by height (cm) - 100\].

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 25, 2020
• Study Start: July 30, 2020
• Primary Completion: July 25, 2021
• Study Completion: July 25, 2021
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)