FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2024/06/069119 [Registered on: 18/06/2024] Trial Registered Prospectively
Last Modified On: 17/06/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Process of Care Changes 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Can Alternate Day Fasting Help Reverse Liver Disease? Insights from the FAST Trial 
Scientific Title of Study   Effect of alternate day fasting over standard medical management alone to reverse non-alcoholic steatohepatitis, A randomized controlled trial. FAST trial 
Trial Acronym  FAST Trial 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Babu Lal Meena 
Designation  Assistant Professor Hepatology 
Affiliation  Institite of Liver and Biliary Sciences 
Address  ILBS, Pocket D1, Vasant Kunj, New Delhi.

South
DELHI
110070
India 
Phone  9781100898  
Fax    
Email  drbabupgi@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Babu Lal Meena 
Designation  Assistant Professor Hepatology 
Affiliation  Institite of Liver and Biliary Sciences 
Address  ILBS, Pocket D1, Vasant Kunj, New Delhi.

South
DELHI
110070
India 
Phone  9781100898  
Fax    
Email  drbabupgi@gmail.com  
 
Details of Contact Person
Public Query  
Name  Babu Lal Meena 
Designation  Assistant Professor Hepatology 
Affiliation  Institite of Liver and Biliary Sciences 
Address  ILBS, Pocket D1, Vasant Kunj, New Delhi.

South
DELHI
110070
India 
Phone  9781100898  
Fax    
Email  drbabupgi@gmail.com  
 
Source of Monetary or Material Support  
Institute of Liver and Biliary Sciences, Pocket D1, Vasant Kunj, New Delhi, India, Pinched-110070 
 
Primary Sponsor  
Name  Intitute of Liver and BIliary Sciences 
Address  Pocket D1, Vasant Kunj, New Delhi. India. Pincode-110070.  
Type of Sponsor  Other [Deemed to be university] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Babu Lal Meena  ILBS Delhi  Room No 3311. 3rd floor, Department of Hepatology, Second phase, Institute of Liver and Biliary Sciences. Pocket D1, Vasant Kunj, New Delhi. India, Pincode-110070.
South
DELHI 		 9781100898

drbabupgi@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Intitutional ethics committee   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K760||Fatty (change of) liver, not elsewhere classified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Alternate day fasting with SMT in the intervention arm.  Alternate day fasting with SMT in the intervention arm. Control arm, SMT only.  
Comparator Agent  Not applicable.  We will compare alternate-day fasting with standard medical management(SMT). The intervention arm subjects will follow the Alternate day fasting with SMT, whereas in the control arm only SMT will be continued. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  NASH patients, Age 18-65 years. BMI 25-40kg/m3, and CAP more than 290. Stable weight in the last 3 months prior to enrolling in the study(less than 5kg weight variation). Imaging showed steatotic liver disease, liver stiffness less than 14kPa measured by fibroscan. Histologically proven NASH/MASH, fibrosis up to F3. Subjects willing to participate in the study 
 
ExclusionCriteria 
Details  Liver stiffness more than 14kPa measured by fibroscan or Fibrosis more than F3. Diabetes with HbA1c more than 8.5%. Patients with another co-existing active liver disease e.g. hepatitis B or C, alcoholic liver disease. Patients with cirrhosis, HCC, or other malignancy. Chronic kidney disease, cardiovascular disorders, uncontrolled hypertension. Chronic infections, chronic inflammatory diseases. Patients on weight loss medications e.g semaglutide. Pregnant or lactating women and those planning a pregnancy. A patient who is not willing to participate in the study, or failed to provide the consent 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
The primary outcome measure is a reversal of NASH over a 24-week duration.  24weeks 
 
Secondary Outcome  
Outcome  TimePoints 
a. Improvement in the quality of life index
b. Reversal of stage of fibrosis
c. No progression of fibrosis
d. Reversal of fat content
e. Quality of life: cardiorespiratory performance
f. Anthropometry
g. Improvement in glycaemic status
h. Decreased liver fat content as measured by fibroscan
i. Change in bone mineral density as measured by DEXA scan
j. Change in faecal microbiota. 		 1, 3 6 months 
 
Target Sample Size   Total Sample Size="90"
Sample Size from India="90" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3/ Phase 4 
Date of First Enrollment (India)   01/07/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   Metabolic liver disease is one of the important causes of morbidity and mortality. Nonalcoholic fatty liver is one of the highly prevalent diseases. NAFLD can progress to NASH and cirrhosis and may cause cirrhosis-related complications. No guideline described the valid treatment for the NASH spectrum of the disorder. Lifestyle modification in the form of dietary intervention and exercise is one of the important strategies for managing NASH. Several lifestyle strategies have been described in the literature. Alternate day fasting is one of the novel modalities that not only restricts the calorie intake but also has other metabolic effect in fatty liver disease and improves the disease state.  However, the role of alternate-day fasting has not been described in patients with NASH. Whether this novel treatment modality has a more beneficial role as compared to standard medical management alone in the reversal of cirrhosis is not known. Hence, we plan this study to explore the new avenue of NASH management. It is hypothesized that alternate-day fasting may have metabolic benefits on the liver, independent of caloric restriction and weight loss, this may also improve NAFLD histology. Induced by extended periods without food, fasting shifts the metabolic circuitry to increase hepatic lipid oxidation, decrease lipogenesis, and use ketones as the primary energy source. Apart from serving as a fuel, ketones enhance the efficacy of mammalian targets of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways and improve the liver’s ability to break down excess triglycerides. Alternate day fasting changes in the microbiome leading to increasing beta-oxidation, improving insulin resistance, and decreasing hepatic lipogenesis.  Furthermore, fasting may be an efficacious non-pharmacological strategy for improving insulin resistance and hepatic steatosis and inflammation without difficulty achieving weight loss and caloric restrictions.
Hence we plan this study to evaluate the role of alternate day fasting. 

Aim and Objective – To compare the role of alternate-day fasting over standard medical management alone to reverse NASH. 

Primary objective: The primary outcome measure is a reversal of NASH over a 24-week duration.

Secondary objectives: Improvement in the quality of life index, Reversal of stage of fibrosis, No progression of fibrosis, Reversal of fat content, Quality of life: cardiorespiratory performance, Anthropometry, Improvement in glycaemic status, Decreased liver fat content as measured by fibroscan, Change in bone mineral density as measured by DEXA scan, Change in faecal microbiota.

 

Methodology 

Study population: This study will be carried out at the Department of Hepatology, Institute of Liver and Biliary Sciences. Patients with NASH attending the ILBS Delhi OPD will be screened for eligibility.

Study design: Open-label, parallel-group, randomized, controlled study. This study is a randomised controlled trial which is designed as per the CONSORT guideline. Patients will be divided into two groups, alternate-day fasting with standard medical management, and standard medical management alone. Subjects will be recruited from the hepatology OPD of the Institute of Liver and Biliary Sciences. New Delhi.

Study design: A randomized controlled trial. Two groups; group A-Alternate day fasting and Group B- Standard medical management

Study period: 1 year after IEC approval.

Inclusion criteria:

NASH patients, Age 18-65 years. BMI 25-40kg/m3, and CAP more than 290. Stable weight in the last 3 months prior to enrolling in the study(<5kg weight variation). Imaging showed steatotic liver disease, liver stiffness <14kPa measured by fibroscan. Histologically proven NASH/MASH, fibrosis up to F3. Subjects willing to participate in the study

Exclusion criteria:

·      Liver stiffness >14kPa measured by fibroscan or Fibrosis >F3. Diabetes with HbA1c>8.5%. Patients with another co-existing active liver disease e.g. hepatitis B or C, alcoholic liver disease. Patients with cirrhosis, HCC, or other malignancy. Chronic kidney disease, cardiovascular disorders, uncontrolled hypertension. Chronic infections, chronic inflammatory diseases. Patients on weight loss medications e.g semaglutide. Pregnant or lactating women and those planning a pregnancy. A patient who is not willing to participate in the study, or failed to provide the consent

Sample size with justification: Assuming that reversal of the NASH in standard treatment is 20% and in the intervention arm it is 50% (that is 30% more than the SMT), with alpha error as 5% and power 80% we need to enrol 76 cases (38 in each). Further assuming a 15% drop outs rate we need to enrol 90 cases. 45 in each group, the allocation will be done randomly by block randomization method, taking block size 10. Considering the drop rate of 20% over the six months, we planned to recruit 36 patients on each arm.

Experimental design

Block randomization will be performed with a computer-generated random number sequence. An independent statistician will generate the allocation sequence, and the study coordinator will assign the subjects to a controlled dietary intervention trial for 24 weeks as the subjects enrolled. Subjects will be randomised using the stratified random sample to groups: group A) Intervention group, and group B) Control group.

Intervention:

Individuals with alternate-day fasting groups will be advised to pre-fixed meal intake to fulfil the 25% of the daily calorie requirement on fasting day(for 24 hours), and then ad libitum calorie intake on the feed day(24 hrs). The control group will be advised to consume 80% of the daily dietary requirement without any restrictions on lifestyle patterns. Mifflin equation to be used to calculate the daily calorie requirement. Feed and fast days will begin at midnight. Feeding times will be fixed. Intake of energy-free beverages e.g. tea, coffee, and sugar-free gums will be permitted. Participants will be ensured to consume plenty of water. Exercise for 150minutes in a week will be advised to the both groups. Exercise in ADF group will be enforced preferably on the feed days.

Monitoring and assessment:

Patients will be evaluated at the 2weeks, 4 weeks initially then every monthly. In the follow up anthropometric examination will be done at each visit. Liver function tests and fibroscan will be done at 3 and six months of the follow-up. Dietary follow up will be ensured by maintaining the daily food diary. A daily whatsapp reminder will be sent to the patients about the feed or fast day. 

Statistical Analysis:

The results will be reported as counts and percentages for categorical variables, and as mean ± SD (range) for continuous normally distributed variables and median (interquartile range [IQR]) for ordinal categorical variables and for continuous non-normally distributed variables. The chi-square test will be used for cross-tabulations. Continuous variables will be compared between the groups by using the Student’s t-test or the Mann-Whitney test, depending on the data distribution.

Adverse effects:

The adverse effects will be classified as none, remote, possible, probable or not assessable based on the relation with the intervention.

Stopping rule of study:

The study will be stopped in case of life-threatening adverse event judged to be related to the protocol intervention at the department review meeting.

Expected outcome of the project:

Establishment of an effective treatment protocol for patients with NASH. 

Ethical issues in the study and plans to address these issues:

We foresee no ethical issue in the current study as the protocol involves treating the ongoing morbid condition. The treatment involves home-based dietary intervention for the treatment of the patients. The study is easy to conduct and requires no extra intervention or cost burden to the patient.

 
Close