Clinical trial NCT03791203: Effectiveness and Adherence of Modified Alternate-day Calorie Restriction (MACR) in Non-Alcoholic Fatty Liver Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: Non-alcoholic fatty liver disease
Lead sponsor: Universiti Sains Malaysia
Sponsor class: OTHER
First posted: 2019-01-02
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants who fulfilled the selection criteria were randomly assigned to the modified alternate-day calorie restriction (MACR) group or the control group after a 2 week run-in period. During the 2 weeks, participants were required to keep their body weight stable by maintaining their usual eating habits and their daily activities. Randomization was performed using a random number generator with recruitment aimed for three MACR participants for every control participant by principal investigator.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline shear wave elastography (SWE) at 8 weeks
timeFrame: Change from baseline at 8-week
measure: Change from baseline liver steatosis at 8 weeks
timeFrame: Change from baseline at 8-week
measure: Concentration of high-density lipoprotein (HDL)
timeFrame: Change from baseline at 8-week
measure: Concentration of low-density lipoprotein (LDL)
timeFrame: Change from baseline at 8-week
measure: Concentration of triglycerides (TG)
timeFrame: Change from baseline at 8-week
measure: Concentration of total cholesterol (TC)
timeFrame: Change from baseline at 8-week
measure: Concentration of fasting blood sugar (FBS)
timeFrame: Change from baseline at 8-week
measure: Concentration of alanine aminotransferase (ALT)
timeFrame: Change from baseline at 8-week
measure: Concentration of aspartate aminotransferase (AST)
timeFrame: Change from baseline at 8-week
Secondary outcomes:
measure: Dietary plan adherence
timeFrame: At 8-week
Other outcomes:
Locations:
Study officials:
affiliation: Universiti Sains Malaysia
name: Yeong Yeh Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: