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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04283942
• Other study ID #: B2019-256R
• Status: Completed
• Phase: N/A
• Start date: July 30, 2020
• Est. completion date: July 25, 2021

Study information

• Verified date: September 2023
• Source: Shanghai Zhongshan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 25, 2021
• Est. primary completion date: July 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria

• Age 18-70
• Diagnosed as fatty liver by ultrasound or magnetic resonance imaging
• BMI = 24 kg/m2
• abnormal glucose metabolism: (meeting at least one):

1. Impaired glucose regulation: fasting blood glucose = 100 mg/dL, postprandial blood glucose = 140 mg/dL or HbA1c = 5.7%

2. 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 Exclusion Criteria

• 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
• Absent of informed consent

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Fatty Liver
• Fatty Liver Disease
• Impaired Glucose Regulation
• Liver Diseases
• Type 2 Diabetes

Intervention

Behavioral:
• Intermittent calorie restriction (ICR)
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)
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.

Locations

Country	Name	City	State
China	Zhongshan Hospital, Fudan University	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (16)

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* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of fat mass	measured by bioimpedance analyzer, fat mass in kilograms.	12 weeks
Other	Change of lean mass	measured by bioimpedance analyzer, skeletal muscle mass in kilograms.	12 weeks
Other	Change of abdominal adiposity	measured by MRI, including visceral adipose tissue and subcutaneous adipose tissue, all in square centimetres.	12 weeks
Other	Change of liver stiffness measure of liver transient elastography	Change of liver stiffness measure of liver transient elastography, in kPa.	12 weeks
Other	Change of insulin sensitivity	Change of HOMA-IR (fasting glucose in mmol/L x fasting insulin in µU/mL)/22.5).	12 weeks
Other	Change of fasting insulin	Change of fasting insulin in µU/mL.	12 weeks
Other	Change of brain functional MRI	Brain functional MRI will be used to evaluate the neural activity of the brain.	12 weeks
Primary	Change of liver fat content in %	Change of liver fat content in %.	12 weeks
Secondary	Change of weight	Change of weight in kilograms.	12 weeks
Secondary	Change of blood glucose: fasting blood glucose	Change of fasting blood glucose in mmol/L.	12 weeks
Secondary	Change of blood glucose: 2h postload blood glucose	Change of 2h postload blood glucose in mmol/L.	12 weeks
Secondary	Change of HbA1c	Change of HbA1c in %.	12 weeks
Secondary	Change of liver enzymes: alanine aminotransferase	Change of alanine aminotransferase in U/L.	12 weeks
Secondary	Change of liver enzymes: aspartate aminotransferase	Change of aspartate aminotransferase in U/L.	12 weeks
Secondary	Change of liver enzymes: ?-glutamyl transpeptidase	Change of ?-glutamyl transpeptidase in U/L.	12 weeks
Secondary	Change of lipid profile: total cholesterol	Change of total cholesterol in mmol/L.	12 weeks
Secondary	Change of lipid profile: triglyceride	Change of triglyceride in mmol/L.	12 weeks
Secondary	Change of lipid profile: high-density lipoprotein-cholesterol	Change of high-density lipoprotein-cholesterol in mmol/L.	12 weeks
Secondary	Change of lipid profile: low-density lipoprotein-cholesterol	Change of low-density lipoprotein-cholesterol in mmol/L.	12 weeks
Secondary	Change of lipid profile: free fatty acid	Change of free fatty acid in mmol/L.	12 weeks