Non-Alcoholic Fatty Liver DiseaseNCT03791203
Effectiveness and Adherence of Modified Alternate-day Calorie Restriction (MACR) in Non-Alcoholic Fatty Liver Disease
A study testing Calorie restriction (MACR) in people with Non-Alcoholic Fatty Liver Disease, run by Universiti Sains Malaysia.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Calorie restriction (MACR)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2015to 1 Oct 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
About this study
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
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.
Read the 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.
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Being tested
- Calorie restriction (MACR)
- Keywords
- Non-alcoholic fatty liver disease
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Calorie restriction (MACR)Behavioural
Also called Modified Alternate-day 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.
| Study group | Role | What they receive |
|---|---|---|
| Calorie restriction (MACR) | Experimental | Participants restricted 70% of their energy needs over 24 hours on a calorie restriction day alternate with a feeding day for the next 24 hours, where they were allowed eating (ad libitum). The calorie restriction and feeding days begun at 9 am each day, and on the calorie restriction day, meals were consumed between 2 pm and 8 pm to ensure that they underwent the same duration of calorie restriction. On each calorie restriction day, they were allowed energy-free beverages and sugar-free gum and encouraged to drink plenty of water. Diet plans were self-selected using detailed individualized food portion lists, meal plans, and recipes. Participants received phone calls from the investigator and four 2-weekly appointments with a dietitian. Adverse experiences were assessed every 2 weeks. Receives: Behavioral: Calorie restriction (MACR) |
| Control group | No intervention | Participants in the control group continued their usual habitual diet for 8 weeks. No specific dietary advice or educations were provided throughout the entire trial. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Change from baseline at 8-week
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%.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
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.
Measured: Change from baseline at 8-week
Secondary outcomes (1)
Dietary plan adherence
Adherence data were assessed each week as percentage of adherence
Measured: At 8-week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2019
- Study start1 Aug 2015
- Primary completion31 Jul 2017
- Study completion1 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiti Sains Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Muhammad Izzad Bin Johari, Universiti Sains Malaysia
- Investigators
- Yeong Yeh Lee, MD, PhD, Principal investigator, Universiti Sains Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03791203
- Sponsor's protocol ID
- 304/PPSP/61313173
- Status last verified
- Dec 2018
- First submitted
- 16 Dec 2018
- Last updated
- 2 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03791203
- Acronym / sponsor ID
- 304/PPSP/61313173
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Keywords
- Non-alcoholic fatty liver disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Universiti Sains MalaysiaUniversity, hospital or other
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 1 Oct 2017 (actual)
- First posted
- 2 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Calorie restriction (MACR) | Experimental | Behavioral: Calorie restriction (MACR)Participants restricted 70% of their energy needs over 24 hours on a calorie restriction day alternate with a feeding day for the next 24 hours, where they were allowed eating (ad libitum). The calorie restriction and feeding days begun at 9 am each day, and on the calorie restriction day, meals were consumed between 2 pm and 8 pm to ensure that they underwent the same duration of calorie restriction. On each calorie restriction day, they were allowed energy-free beverages and sugar-free gum and encouraged to drink plenty of water. Diet plans were self-selected using detailed individualized food portion lists, meal plans, and recipes. Participants received phone calls from the investigator and four 2-weekly appointments with a dietitian. Adverse experiences were assessed every 2 weeks. |
| Control group | No intervention | –Participants in the control group continued their usual habitual diet for 8 weeks. No specific dietary advice or educations were provided throughout the entire trial. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Calorie restriction (MACR)Also: Modified Alternate-day 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. | Behavioural | Calorie restriction (MACR) |
Primary outcome
Change from baseline shear wave elastography (SWE) at 8 weeks
Time frame: Change from baseline at 8-week
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 liver steatosis at 8 weeks
Time frame: Change from baseline at 8-week
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%.
Concentration of high-density lipoprotein (HDL)
Time frame: Change from baseline at 8-week
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.
Concentration of low-density lipoprotein (LDL)
Time frame: Change from baseline at 8-week
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.
Concentration of triglycerides (TG)
Time frame: Change from baseline at 8-week
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.
Concentration of total cholesterol (TC)
Time frame: Change from baseline at 8-week
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.
Concentration of fasting blood sugar (FBS)
Time frame: Change from baseline at 8-week
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.
Concentration of alanine aminotransferase (ALT)
Time frame: Change from baseline at 8-week
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.
Concentration of aspartate aminotransferase (AST)
Time frame: Change from baseline at 8-week
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.
1 secondary outcome
Dietary plan adherence
Time frame: At 8-week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yeong Yeh Lee, MD, PhD principal investigator
Universiti Sains Malaysia
Questions about this trial
What is this clinical trial studying?
A study testing Calorie restriction (MACR) in people with Non-Alcoholic Fatty Liver Disease, run by Universiti Sains Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline shear wave elastography (SWE) at 8 weeks (time frame: Change from baseline at 8-week). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2019.