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Trial registered on ANZCTR


Registration number
ACTRN12613000935730
Ethics application status
Approved
Date submitted
14/08/2013
Date registered
26/08/2013
Date last updated
14/08/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Non-alcoholic fatty liver disease Intermittent Fasting Time Intervention
Scientific title
A 24 week randomised controlled cross-over pilot study assessing the effects of an 8 hr time restricted feeding regime or standard dietary advice on hepatic steatosis, visceral fat and biochemical parameters of metabolic syndrome in adults with non-alcoholic fatty liver disease.
Secondary ID [1] 282953 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
NIFTI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
fatty liver 289781 0
visceral adiposity 289863 0
Condition category
Condition code
Oral and Gastrointestinal 290129 290129 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Diet and Nutrition 290130 290130 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects allocated to the intermittent fasting (IF) arm will be instructed to withhold all food and energy containing drinks for 16 hours from 8pm until 12 noon the following day. During this time, water, black tea and black coffee are permitted. Between the hours of noon and 8pm, subjects are able to consume food as desired. Those in the IF intervention proceed for 12 weeks upon which time participants will "cross over" to the standard dietary advice group for an additional 12 weeks (total of 24 weeks). There is no wash-out period per se. This latter 12 weeks to to determine how long the effects of IF last.
The "control" or standard dietary intervention group will proceed for 12 weeks upon which time they "cross over" to have IF for 12 weeks (total 24 weeks). There is no wash out period.
To determine adherence to lifestyle management strategies (IF or control) each subject will complete a 3 day total food diary. The first will be complete at baseline and then every 2 weeks for the total 24 weeks. Participants will also be contacted every 2 weeks by an investigator to give encouragement and answer any questions that may arise. Participants will be given a mobile phone number that they can contact during working hours if they need assistance or have questions between the 2 weekly phone calls.
Intervention code [1] 287664 0
Lifestyle
Comparator / control treatment
The standard therapy arm will be instructed to follow the general lifestyle and diet advice as explained in the non-alcoholic fatty liver disease (NAFLD) information sheet of the Gastroenterological Society of Australia (GESA). This will involve the following.
1.) If overweight patients will be instructed to begin a weight management program with the goal of a gradual 0.25 to 0.5 kg weight loss a week.
2.) If central adiposity present then to aim for a waistline of
80cm (or less) if female or 95cm (or less) if male.
3.) Exercise at least 5 days a week which consists of both aerobic and resistance exercise.
4.) Eat a healthy diet low in fat and calories but high in fibre.
Participants will be asked to refer to the GESA information sheet on fatty liver for further information.
Control group
Active

Outcomes
Primary outcome [1] 290159 0
The co-primary endpoints of this study are to demonstrate IF can: 1.) reduce the volume of visceral fat from baseline by 25% in subjects with NAFLD after 12 weeks. This endpoint will be determined by single abdominal slice CT of visceral fat volume and body composition measurement of abdominal fat weight.
Timepoint [1] 290159 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. Outcomes will be assessed at baseline, 12 and finally at 24 weeks.
Primary outcome [2] 290246 0
2.) reduce hepatic steatosis from baseline by 25% as determined by Fibroscan (controlled attenuation parameter measurement)
Timepoint [2] 290246 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. Fibroscan will be done at baseline, 12 and finally 24 weeks.
Secondary outcome [1] 304034 0
Alanine aminotransferase (ALT) as measured by blood test.
Timepoint [1] 304034 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. ALT will be measured at baseline, 4, 8, 12, 16, 20 and 24 weeks.
Secondary outcome [2] 304196 0
insulin resistance as calculate by Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) using fasting insulin and glucose blood tests.
Timepoint [2] 304196 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. These outcomes will be measured at baseline, 4, 8, 12, 16, 20 and 24 weeks.
Secondary outcome [3] 304197 0
body weight as measured by medical grade scales.
Timepoint [3] 304197 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. This outcome will be measured at baseline, 4, 8, 12, 16, 20 and 24 weeks.
Secondary outcome [4] 304198 0
lipid profile as measured by blood tests for total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides (TG).
Timepoint [4] 304198 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. These outcomes will be measured at baseline, 12 and 24 weeks.
Secondary outcome [5] 304199 0
adipocytokine profile as measured by Enzyme-linked immunosorbent assay (ELISA) for adiponection and leptin.
Timepoint [5] 304199 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. These outcomes will be measured at baseline, 12 and 24 weeks.
Secondary outcome [6] 304200 0
faecal calprotectin as measured by ELISA
Timepoint [6] 304200 0
12 weeks of either IF or standard therapy then each patient switches (crosses over) to the alternative arm for another 12 weeks. This outcome will be measured at baseline, 12 and 24 weeks.

Eligibility
Key inclusion criteria
1.) adults age 18-75 yrs
2.) fatty liver on ultrasound
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.) alcohol intake => 30g/day in men or =>20g/day in women or history of consistent excessive alcohol intake in last 10 years
2.) presence of hepatitis B (HBsAg +ve) or Hepatitis C (HCV PCR +ve), or any other causes of liver disease
3.) Type 2 diabetes mellitus on insulin therapy
4.) pregnant or breast-feeding
5.) cirrhosis as determined either previous liver biopsy or by Fibroscan liver stiffness measurement (LSM > 14kPA) and/or clinical features of decompensated liver disease
6.) current therapy with magnesium or aluminium containing antacids, anticonvulsants, barbiturates, primidone, calcitonin, etidronate, pamidronate, thiazide diuretics, cholestyramine, digoxin, milk thistle, hepatic-enzyme inhibitors, or vitamin E
7.) current therapy with drugs known to cause steatohepatitis: corticosteroids, tamoxifen, amiodarone, methotrexate, high-dose oestrogens
8.) current therapy with thiazolidinediones
9.) inability to provide informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
patients randomly assigned (by computer) to lifestyle intervention or standard care
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
one of the two study investigators will be blinded to what group each subject is in as he will be performing Fibroscan on the subjects.
Subjects will be instructed not to inform this investigator of their group.
Phase
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size determination:
Based on a previous validation study of Continuous Attenuation Parameter (CAP) with Fibroscan for assessing steatosis, where the median value for patients with steatosis was 317 dB/m and 250 for those without minimal steatosis, aiming for a conservative response with a decrease from 317 dB/m to 280 dB/m with an estimated standard deviation of 50, using analysis to compare two means, we would need 29 patients in each group (58 in total) to achieve this endpoint. (used OpenEpi to calculate size: 222.openepi.com/OE2.3/SampleSize/SSMean.htm)

Data analysis: Categorical variables will be analysed using the Chi2 test, continuous variable will be compared using the Mann-Whitney U-test, and linear regression will be performed using Stata 12 software, with a p value <0.05 considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1389 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 7251 0
3940 - Rosebud West
Recruitment postcode(s) [2] 7252 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 287732 0
University
Name [1] 287732 0
Monash University
Address [1] 287732 0
Clayton campus
Wellington Road
Clayton
Victoria 3800
Country [1] 287732 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Clayton campus
Wellington Road
Clayton
Victoria 3800
Country
Australia
Secondary sponsor category [1] 286459 0
None
Name [1] 286459 0
Address [1] 286459 0
Country [1] 286459 0
Other collaborator category [1] 277565 0
Hospital
Name [1] 277565 0
Diagnostic Imaging

Address [1] 277565 0
Radiology department
Monash Medical Centre
246 Clayton Road
Clayton, Victoria 3168
Country [1] 277565 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289687 0
Southern Health Human Research Ethics A
Ethics committee address [1] 289687 0
Research Directorate
Southern Health
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Ethics committee country [1] 289687 0
Australia
Date submitted for ethics approval [1] 289687 0
Approval date [1] 289687 0
14/01/2013
Ethics approval number [1] 289687 0
12298A

Summary
Brief summary
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide affecting 15 to 45% of the adult population. NAFLD is a spectrum from simple fat (NAFLD) to fat and inflammation (non-alcoholic steatohepatitis (NASH). Ten to 25% of NASH cases progress onto advanced hepatic fibrosis and cirrhosis with its complications of end stage liver disease and liver cancer. NAFLD is part of a group of medical conditions called the metabolic syndrome. These include type-2 diabetes, high blood pressure, high cholesterol and abdominal obesity. The presence of NAFLD is also associated with wide ranging health problems including obstructive sleep apnoea, polycystic ovary syndrome, colon polyps, hypothyroidism and vitamin D deficiency.
This project aims to assess whether NAFLD can be improved by undertaking a controlled period of fasting. Previous research has shown that controlled periods of fasting can improve diabetes and cholesterol in these patients but no one has ever looked at NAFLD. This project will involve approximately 60 people in two groups all at Monash Health. Each group will contain 30 people. One group will follow a diet plan that involves a period of controlled fasting during each day from 8pm at night until 12pm the following day, while the other will follow the current Gastoenterological Society of Australia standard treatment guidelines for NAFLD. At 12 weeks, participants will be invited to take part in the other treatment group for a further 12 weeks (a total of 24 weeks). Each study participant will have a series of assessments done at baseline and at various points throughout the study. This will include anthropometric measurements, abdominal fat content via single slice CT scan, Fibroscan for liver steatosis, body composition (fat and lean muscle mass) and blood tests.
After 12 weeks we hope to see a 25% improvement in the amount of abdominal and liver fat from baseline. Other intended improvements may be in blood markers of inflammation and metabolism.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41950 0
Dr Gregory Moore
Address 41950 0
Gastroenterology & Hepatology Unit
Department of Medicine, Monash University
Monash Medical Centre, 246 Clayton Road, Clayton Vic 3168
Country 41950 0
Australia
Phone 41950 0
+61-3-9594-3177
Fax 41950 0
61-3-9594-6250
Email 41950 0
niftistudy@gmail.com
Contact person for public queries
Name 41951 0
Dr Alexander Hodge
Address 41951 0
Gastroenterology & Hepatology Unit
Department of Medicine, Monash University
Monash Medical Centre, 246 Clayton Road, Clayton Vic 3168
Country 41951 0
Australia
Phone 41951 0
+61-3-9594-3177
Fax 41951 0
61-3-9594-6250
Email 41951 0
niftistudy@gmail.com
Contact person for scientific queries
Name 41952 0
Dr Alexander Hodge
Address 41952 0
Gastroenterology & Hepatology Unit
Department of Medicine, Monash University
Monash Medical Centre, 246 Clayton Road, Clayton Vic 3168
Country 41952 0
Australia
Phone 41952 0
+61-3-9594-3177
Fax 41952 0
61-3-9594-6250
Email 41952 0
niftistudy@gmail.com

No information has been provided regarding IPD availability
Summary results
No Results