AzTrials
AzTrials

Fatty Liver DiseaseNCT04283942

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

A study testing Intermittent calorie restriction (ICR) and Continuous calorie restriction (CCR) in people with Fatty Liver Disease and Type 2 Diabetes, run by Shanghai Zhongshan Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Intermittent calorie restriction (ICR) and Continuous calorie restriction (CCR)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteChina
Study dates
30 Jul 2020to 25 Jul 2021
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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
  • Absent of informed consent

Trial locations and contacts

1 site in 1 country.

China1 site
  • Zhongshan Hospital, Fudan University

    Shanghai

Other trials in China

About this study

Official title: Effect of Intermittent Calorie Restriction on Metabolic Dysfunction-Associated Steatotic Liver Disease Patients With Abnormal Glucose Metabolism

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.

Read the detailed description

Intermittent caloric restriction (ICR) can effectively reduce weight and facilitate blood glucose control, but whether it can be applied for clinical treatment to metabolic dysfunction-associated steatotic liver disease (MASLD) patients remains unclear. We intend to carry out this study in MASLD patients with abnormal glucose metabolism. It is an open-labeled randomized trial 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. 60 patients will be randomly divided into ICR group and control group for 12 weeks of 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. The daily calories intake for control group should be: 25 kcal / kg × [height (cm) - 100] kg. Daily food diary is required in both groups. During the experiment, all subjects should maintain their exercise routine. The use of drugs affecting blood glucose and fatty liver should be avoided. After 12 weeks of intervention, the changes of liver fat content were evaluated by magnetic resonance spectroscopy (MRS) and Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF). The effects of ICR on body weight, blood glucose and body fat will also be evaluated. Both groups will be followed up on their changes of weight 4 weeks after intervention.

Being tested
Intermittent calorie restriction (ICR), Continuous calorie restriction (CCR)
Keywords
Metabolic dysfunction-associated steatotic liver disease, Type 2 Diabetes
Medical subject headings
Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intermittent calorie restriction (ICR)Behavioural

    Also called Intermittent fasting

    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.

  • Continuous calorie restriction (CCR)Behavioural

    Also called Daily calorie restriction

    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.

Study groups in NCT04283942
Study groupRoleWhat they receive
Intermittent Calorie Restriction (ICR)ExperimentalParticipants 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.
Receives: Behavioral: Intermittent calorie restriction (ICR)
Control (Continuous calorie restriction, CCR)OtherParticipants 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.
Receives: Behavioral: Continuous calorie restriction (CCR)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of Liver Fat Content in %

    Change of liver fat content in %.

    Measured: From baseline to week 12

Secondary outcomes (12)
  1. Change of Weight

    Change of weight in kilograms.

    Measured: From baseline to week 12

  2. Change of Blood Glucose: Fasting Blood Glucose

    Change of fasting blood glucose in mg/dL.

    Measured: From baseline to week 12

  3. Change of Blood Glucose: 2h Postload Blood Glucose

    Change of 2h postload blood glucose in mg/dL.

    Measured: From baseline to week 12

  4. Change of HbA1c

    Change of HbA1c in %.

    Measured: From baseline to week 12

  5. Change of Liver Enzymes: Alanine Aminotransferase

    Change of alanine aminotransferase in U/L.

    Measured: From baseline to week 12

  6. Change of Liver Enzymes: Aspartate Aminotransferase

    Change of aspartate aminotransferase in U/L.

    Measured: From baseline to week 12

  7. Change of Liver Enzymes: γ-glutamyl Transpeptidase

    Change of γ-glutamyl transpeptidase in U/L.

    Measured: From baseline to week 12

  8. Change of Lipid Profile: Total Cholesterol

    Change of total cholesterol in mg/dL.

    Measured: From baseline to week 12

  9. Change of Lipid Profile: Triglyceride

    Change of triglyceride in mg/dL.

    Measured: From baseline to week 12

  10. Change of Lipid Profile: High-density Lipoprotein-cholesterol

    Change of high-density lipoprotein-cholesterol in mg/dL.

    Measured: From baseline to week 12

  11. Change of Lipid Profile: Low-density Lipoprotein-cholesterol

    Change of low-density lipoprotein-cholesterol in mg/dL.

    Measured: From baseline to week 12

  12. Change of Lipid Profile: Free Fatty Acid

    Change of free fatty acid in mg/dL.

    Measured: From baseline to week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2020
  2. Study start30 Jul 2020
  3. Primary completion25 Jul 2021
  4. Study completion25 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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 \[kg, estimated by height (cm) - 100\].
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04283942
Sponsor's protocol ID
B2019-256R
Status last verified
Jun 2024
First submitted
21 Feb 2020
Last updated
23 Sep 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Feb 22.

    PubMed 26707365
  • Fan JG, Kim SU, Wong VW. New trends on obesity and NAFLD in Asia. J Hepatol. 2017 Oct;67(4):862-873. doi: 10.1016/j.jhep.2017.06.003. Epub 2017 Jun 19.

    PubMed 28642059
  • Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol. 2013 Aug;28 Suppl 1:11-7. doi: 10.1111/jgh.12036.

    PubMed 23855290
  • 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.

    PubMed 25164003
  • Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002 Apr 18;346(16):1221-31. doi: 10.1056/NEJMra011775. No abstract available.

    PubMed 11961152
  • 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.

    PubMed 26667191
  • 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.

    PubMed 12031978
  • 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.

    PubMed 24002776
  • Musso G, Gambino R, Tabibian JH, Ekstedt M, Kechagias S, Hamaguchi M, Hultcrantz R, Hagstrom H, Yoon SK, Charatcharoenwitthaya P, George J, Barrera F, Hafliethadottir S, Bjornsson ES, Armstrong MJ, Hopkins LJ, Gao X, Francque S, Verrijken A, Yilmaz Y, Lindor KD, Charlton M, Haring R, Lerch MM, Rettig R, Volzke H, Ryu S, Li G, Wong LL, Machado M, Cortez-Pinto H, Yasui K, Cassader M. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014 Jul 22;11(7):e1001680. doi: 10.1371/journal.pmed.1001680. eCollection 2014 Jul.

    PubMed 25050550
  • 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.

    PubMed 15842581
  • 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.

    PubMed 30475966
  • 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.

    PubMed 28202779
  • 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.

    PubMed 28235195
  • 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.

    PubMed 31375753
  • 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.

    PubMed 30475957

Questions about this trial

What is this clinical trial studying?

A study testing Intermittent calorie restriction (ICR) and Continuous calorie restriction (CCR) in people with Fatty Liver Disease and Type 2 Diabetes, run by Shanghai Zhongshan Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of Liver Fat Content in % (time frame: From baseline to week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04283942, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in