Effectiveness and Adherence of Modified Alternate-day Calorie Restriction (MACR) in Non-Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease Clinical Trial

Official title:

A Randomized Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction (MACR) in Improving Activity of Non-Alcoholic Fatty Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03791203
• Other study ID #: 304/PPSP/61313173
• Status: Completed
• Phase: N/A
• Start date: August 1, 2015
• Est. completion date: October 1, 2017

Study information

• Verified date: December 2018
• Source: University of Science Malaysia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. Currently, there are no studies had been focusing the effect of Modified Alternate Day Calorie Restriction in NAFLD patient focusing on changes in liver steatosis and fibrosis.

Description:

Disease activity and progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) and cirrhosis can be highly variable, where 2-3% will eventually progress to end-stage liver diseases. With the rising prevalence of metabolic syndrome and obesity, NAFLD has become the most frequent form of chronic liver disease in the West but also in Asia.

There are good evidence that weight loss is effective in improving liver histology in NAFLD, for example, 31 obese patients with NASH was randomised into intensive lifestyle changes over 48 weeks versus structured basic education only, and the intensive lifestyle group showed significant improvements in steatosis, necrosis, and inflammation. Intense calorie restriction is the recommended form of dietary strategy for management of NAFLD. Even though such intense dietary strategy has proven to be effective, some patients find it difficult to adhere and maintain.

On the other hand, intermittent fasting achieves more consistent weight loss by improving adherence, as intermittent fasting only requires calorie restriction every other day compared to conventional form of daily calorie restriction. Alternate day calorie restriction can be divided into two components, a 'feed day' and a 'fast day' where food is consumed ad libitum for 24 hours period alternating with either complete or partial (modified) calorie restriction for the next 24 hours. MACR, the dietary strategy employed in the investigator's study, restricts 70% of an individual's daily requirement of calorie per day. There are other forms of intermittent fasting, for example, 2-4 days of ad libitum feeding alternating with 2-4 days of calorie restriction.

Currently, there are no approved pharmacological therapies for NAFLD, and many guidelines advocate recommendation with a focus on controlling risk factors and lifestyle interventions that include dietary and physical activities. No specific NAFLD trials have evaluated the effectiveness of modified form of intermittent fasting in the control of NAFLD activity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: October 1, 2017
• Est. primary completion date: July 31, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Have elevated ALT or AST level (ALT >41 or AST>34 IU/L)

• No evidence of other forms of liver diseases

• For those with diabetes mellitus and dyslipidaemia, they must be on a stable therapy for at least 6 months prior to study enrolment

Exclusion Criteria:

• Significant alcohol consumption (> 1 standard drink per day)

• Pregnancy

• Involvement in an active weight loss program or taking weight loss medications

• Substance abuse and significant psychiatric problems.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

Behavioral:
• Calorie restriction (MACR)
This was a randomized, single-blind controlled trial with modified alternate-day calorie restriction (MACR) as the active intervention and normal habitual diet as control at Hospital University of Sains Malaysia.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Science Malaysia

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline shear wave elastography (SWE) at 8 weeks	Through the intercostal approach, SWE measurements were performed in the right liver lobe, at the supine position with the right arm in maximal abduction. The sonographer, assisted by an ultrasonic time-motion image, located a liver portion of at least 6 cm thick, free of large vascular structures. Once the measurement area had been located, the sonographer pressed the probe button to start an acquisition. Patients were asked to hold their breath for about five seconds, while the stiffness of the region of interest was measured and 10 measurements were made for each patient and the median average value of those measurements was recorded in kilopascals (kPa: metric).	Change from baseline at 8-week
Primary	Change from baseline liver steatosis at 8 weeks	Ultra-sonographic measurements including liver steatosis and shear wave elastography (SWE) were performed with the SuperSonic Imagine's Aixplorer® Ultrasound machine (Super Sonic Image, Aix-en Provence, France). All measurements were performed by a single sonographer where the inter-observer agreement level with another experienced sonographer was 85%.	Change from baseline at 8-week
Primary	Concentration of high-density lipoprotein (HDL)	Blood samples (8-10 hours of fasting blood samples) were collected from participants at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L.	Change from baseline at 8-week
Primary	Concentration of low-density lipoprotein (LDL)	Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L.	Change from baseline at 8-week
Primary	Concentration of triglycerides (TG)	Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L.	Change from baseline at 8-week
Primary	Concentration of total cholesterol (TC)	Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L.	Change from baseline at 8-week
Primary	Concentration of fasting blood sugar (FBS)	Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L.	Change from baseline at 8-week
Primary	Concentration of alanine aminotransferase (ALT)	Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in U/L.	Change from baseline at 8-week
Primary	Concentration of aspartate aminotransferase (AST)	Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in U/L.	Change from baseline at 8-week
Secondary	Dietary plan adherence	Adherence data were assessed each week as percentage of adherence	At 8-week