Clinical trial NCT04283942: Effect of Intermittent Calorie Restriction on MASLD Patients With Abnormal Glucose Metabolism
Official title: Effect of Intermittent Calorie Restriction on Metabolic Dysfunction-Associated Steatotic Liver Disease Patients With Abnormal Glucose Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fatty Liver Disease
Type 2 Diabetes
Impaired Glucose Regulation
Keywords: Metabolic dysfunction-associated steatotic liver disease
Type 2 Diabetes
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2020-02-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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 \[kg, estimated by height (cm) - 100\].
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of Liver Fat Content in %
timeFrame: From baseline to week 12
Secondary outcomes:
measure: Change of Weight
timeFrame: From baseline to week 12
measure: Change of Blood Glucose: Fasting Blood Glucose
timeFrame: From baseline to week 12
measure: Change of Blood Glucose: 2h Postload Blood Glucose
timeFrame: From baseline to week 12
measure: Change of HbA1c
timeFrame: From baseline to week 12
measure: Change of Liver Enzymes: Alanine Aminotransferase
timeFrame: From baseline to week 12
measure: Change of Liver Enzymes: Aspartate Aminotransferase
timeFrame: From baseline to week 12
measure: Change of Liver Enzymes: γ-glutamyl Transpeptidase
timeFrame: From baseline to week 12
measure: Change of Lipid Profile: Total Cholesterol
timeFrame: From baseline to week 12
measure: Change of Lipid Profile: Triglyceride
timeFrame: From baseline to week 12
measure: Change of Lipid Profile: High-density Lipoprotein-cholesterol
timeFrame: From baseline to week 12
measure: Change of Lipid Profile: Low-density Lipoprotein-cholesterol
timeFrame: From baseline to week 12
measure: Change of Lipid Profile: Free Fatty Acid
timeFrame: From baseline to week 12
Other outcomes:
measure: Change of Fat Mass
timeFrame: From baseline to week 12
measure: Change of Lean Mass
timeFrame: From baseline to week 12
measure: Change of Abdominal Adipose Tissue Area
timeFrame: From baseline to week 12
measure: Change of Liver Stiffness Measure of Liver Transient Elastography
timeFrame: From baseline to week 12
measure: Change of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index
timeFrame: From baseline to week 12
measure: Change of Fasting Insulin
timeFrame: From baseline to week 12
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Hua Bian
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Zhongshan Hospital
name: Xin Gao
role: STUDY_DIRECTOR
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