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Effect of Intermittent Calorie Restriction on NAFLD Patients With Disorders of Glucose Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04283942
Recruitment Status : Completed
First Posted : February 25, 2020
Last Update Posted : August 10, 2022
Sponsor:
Information provided by (Responsible Party):
Hua Bian, Shanghai Zhongshan Hospital

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 NAFLD patients with abnormal blood glucose.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease (NAFLD) Disorders of Glucose Metabolism Type 2 Diabetes Impaired Glucose Regulation Behavioral: Intermittent calorie restriction Behavioral: 25kcal/kg/d diet Not Applicable

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 non-alcoholic fatty liver disease (NAFLD) patients remains unclear. What's more, in order to investigate whether the mechanism of glucose-lowering effect of ICR is related to the decrease of liver fat content, we intend to carry out this study in NAFLD 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 NAFLD patients with abnormal blood glucose. 50 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: 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 × standard weight [kg, male: height (cm) - 105, female: height (cm) - 100]. 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). The effects of ICR on body weight, blood glucose and body fat distribution will also be evaluated. Both groups will be followed up on their changes of weight 4 weeks after intervention.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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: under the guidance of nutritionist, subjects have to learn the method of food calories calculation. For each day, the daily calories intake = 25 kcal / kg × standard weight [kg, estimated by height (cm) - 100].

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Intermittent Calorie Restriction on Non-alcoholic Fatty Liver Disease Patients With Disorders of Glucose Metabolism
Actual Study Start Date : July 30, 2020
Actual Primary Completion Date : July 25, 2021
Actual Study Completion Date : July 25, 2021


Arm Intervention/treatment
Experimental: Intermittent Calorie Restriction (ICR)
Eat only instant nutrition bar in two consecutive days each week, 4 sticks / day, 1 for breakfast, 2 for lunch, 1 for dinner. And the total caloric intake is 497.2kcal/day. In the rest 5 days each week, subjects are allowed ad libitum to their usual food.
Behavioral: Intermittent calorie restriction
Intermittent calorie restriction is a new strategy of reducing weight and improving health. The most common ICR methods include alternative day calorie restriction (ACR) and 5:2 intermittent fasting (fasting 2 days each week). The food consumption in non-fasting day is not limited. We plan to apply the 5:2 intermittent fasting. Intermittent caloric restriction can effectively reduce weight, improve body composition (i.e., reduce fat content while maintaining lean body weight), reduce risk factors of cardiovascular disease (including reducing blood pressure, improving blood lipid level, reducing oxidative stress), and also facilitate blood glucose control (by increasing insulin sensitivity and improving the function of islet β cells).
Other Name: Intermittent fasting

Control
Followed by NAFLD guidelines' recommendation of 25 kcal / kg / day, we only ask them to adjust their daily diet. No experimental foods or drugs are supplied.
Behavioral: 25kcal/kg/d diet
For each day, the daily calories intake = 25 kcal / kg × standard weight [kg, estimated by height (cm) - 100].




Primary Outcome Measures :
  1. Change of liver fat content in % [ Time Frame: 12 weeks ]
    Change of liver fat content in %


Secondary Outcome Measures :
  1. Change of weight [ Time Frame: 12 weeks ]
    Change of weight in kilograms

  2. Change of blood glucose: fasting blood glucose [ Time Frame: 12 weeks ]
    Change of fasting blood glucose in mmol/L

  3. Change of blood glucose: 2h postload blood glucose [ Time Frame: 12 weeks ]
    Change of 2h postload blood glucose in mmol/L

  4. Change of HbA1c [ Time Frame: 12 weeks ]
    Change of HbA1c in %

  5. Change of liver enzymes: alanine aminotransferase [ Time Frame: 12 weeks ]
    Change of alanine aminotransferase in U/L

  6. Change of liver enzymes: aspartate aminotransferase [ Time Frame: 12 weeks ]
    Change of aspartate aminotransferase in U/L

  7. Change of liver enzymes: γ-glutamyl transpeptidase [ Time Frame: 12 weeks ]
    Change of γ-glutamyl transpeptidase in U/L

  8. Change of lipid profile: total cholesterol [ Time Frame: 12 weeks ]
    Change of total cholesterol in mmol/L

  9. Change of lipid profile: triglyceride [ Time Frame: 12 weeks ]
    Change of triglyceride in mmol/L

  10. Change of lipid profile: high-density lipoprotein-cholesterol [ Time Frame: 12 weeks ]
    Change of high-density lipoprotein-cholesterol in mmol/L

  11. Change of lipid profile: low-density lipoprotein-cholesterol [ Time Frame: 12 weeks ]
    Change of low-density lipoprotein-cholesterol in mmol/L

  12. Change of lipid profile: free fatty acid [ Time Frame: 12 weeks ]
    Change of free fatty acid in mmol/L


Other Outcome Measures:
  1. Change of body fat percentage [ Time Frame: 12 weeks ]
    measured by InBody520, body fat percentage in % adipose tissue [SAT])

  2. Change of skeletal muscle mass [ Time Frame: 12 weeks ]
    measured by InBody520, skeletal muscle mass in kilograms

  3. Change of abdominal adiposity [ Time Frame: 12 weeks ]
    measured by MRI, visceral adipose tissue and subcutaneous adipose tissue, all in square centimetres.

  4. Change of liver stiffness measure of liver transient elastography [ Time Frame: 12 weeks ]
    Change of liver stiffness measure of liver transient elastography, in kPa

  5. Change of insulin sensitivity [ Time Frame: 12 weeks ]
    Change of HOMA-IR (fasting glucose in mmol/L x fasting insulin in μU/mL)/22.5)

  6. Change of fasting insulin [ Time Frame: 12 weeks ]
    Change of fasting insulin in μU/mL

  7. Change of brain functional MRI [ Time Frame: 12 weeks ]
    Brain functional MRI will be used to evaluate the neural activity of the brain



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-70
  2. diagnosed as fatty liver
  3. BMI≥24 kg/m2
  4. The diagnostic criteria for abnormal glucose metabolism are as follows (meeting at least one):

    1. Impaired glucose regulation: fasting blood glucose ≥ 5.6 mmol / L, postprandial blood glucose ≥ 7.8 mmol / L or HbA1c ≥ 5.7%.
    2. Diabetes mellitus: diabetic symptoms + plasma glucose concentration ≥ 11.1 mmol / L at any time or fasting plasma glucose concentration ≥ 7.0 mmol / L or OGTT 2 h plasma glucose concentration ≥ 11.1 mmol / L.

Exclusion Criteria:

  1. Type 1 diabetes, gestational diabetes and other special types of diabetes
  2. Poor blood glucose control, HbA1c > 8.5% within 3 months
  3. Had antidiabetic drugs in the past month
  4. Serum ALT was more than 6 times of normal upper limit
  5. Excessive alcohol consumption (definition: in the past 6 months, alcohol intake: men > 140g, women > 70g)
  6. Other liver diseases: such as acute and chronic viral hepatitis, drug-induced hepatitis, immune hepatitis, liver cirrhosis, liver cancer, etc
  7. Had drugs that may affect NAFLD in the past three months, such as vitamin E
  8. Biliary diseases: biliary obstructive diseases, etc
  9. Other diseases affecting glycolipid metabolism: hyperthyroidism, hypothyroidism, Cushing's syndrome, etc
  10. Chronic kidney disease (serum creatinine ≥ 2.0mg/dl)
  11. Life expectancy of no more than 5 years
  12. Already pregnant or plan to be pregnant in the near future
  13. Mental illness
  14. Other conditions affecting follow-up
  15. Participated in other clinical trials in the past 4 weeks
  16. Absent of informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04283942


Locations
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China
Zhongshan Hospital, Fudan University
Shanghai, China
Sponsors and Collaborators
Shanghai Zhongshan Hospital
Investigators
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Principal Investigator: Hua Bian Shanghai Zhongshan Hospital
Study Director: Xin Gao Shanghai Zhongshan Hospital
Publications:

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Responsible Party: Hua Bian, Director, Shanghai Zhongshan Hospital
ClinicalTrials.gov Identifier: NCT04283942    
Other Study ID Numbers: B2019-256R
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: August 10, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hua Bian, Shanghai Zhongshan Hospital:
Non-Alcoholic Fatty Liver Disease
Type 2 Diabetes
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Diabetes Mellitus
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases