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Trial registered on ANZCTR


Registration number
ACTRN12612000841875
Ethics application status
Not yet submitted
Date submitted
7/08/2012
Date registered
10/08/2012
Date last updated
10/08/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Non-alcoholic Fatty Liver Disease Dietary Trial
Scientific title
For a patient with non-alcoholic fatty liver disease, will an isocaloric Mediterranean diet as compared to standard care with a low-fat diet, improve hepatic steatosis and cardiovascular risk factors?
Secondary ID [1] 280984 0
Nil
Universal Trial Number (UTN)
U1111-1133-0372
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic fatty liver disease 287104 0
Presence of cardiovascular risk factors 287105 0
Condition category
Condition code
Oral and Gastrointestinal 287429 287429 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cardiovascular 287430 287430 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Mediterranean diet, the composition of which is high fat, high monounsaturated fat, controlled saturated fat, moderate carbohydrate. The diet will be administered to the patient group for a period of 12 weeks. The diet will be isocaloric, to avoid inducing weight loss in the intervention population, which has known beneficial effects on the primary outcome measure of hepatic steatosis.
The composition of the Mediterranean diet will be based on analysis of the 1960's Cretan Mediterranean diet:
40% of energy as carbohydrate;
35-40% of energy as fat with <10-15% of energy as saturated fat, <0.5% trans fatty acids;
20% of energy as protein.
The total energy content of the diet will be individualised based on standard energy estimation equations. A pre-prepared diet, based on that level of energy (to the nearest 500kJ) will then be used to educate the subject. Subjects will be given lists of appropriate foods within each food group, they will be told how many serves of each group they need to consume per day and per week, and they will be given detailed information about what constitutes a 'serve' of each food. This will be combined with an individualised 'sample meal plan' which will be based on the usual patterns of intake of the subject. This is consistent with methods used by Dietitians in the administration of medical nutrition therapy and is designed to increase compliance, rather than imposing a pre-determined pattern of eating (eg. 3 meals per day), which may be highly inconsistent with the subjects normal eating patterns.
Intervention code [1] 285428 0
Treatment: Other
Intervention code [2] 285453 0
Lifestyle
Comparator / control treatment
A standard care diet (low-fat, high carbohydrate, controlled saturated fat) will be administered to a control group for a period of three months. The diet is isocaloric, to avoid inducing weight loss in the group.
The standard care diet is based on the ‘Therapeutic Lifestyle Changes’ diet (which is one of the regimes recommended by the American heart association). This is a low fat, high carbohydrate diet with the following composition:
50-55% of energy as carbohydrate;
25% of energy as fat;
15-20% of energy as protein.
As per the treatment diet, energy content will be individualised based on standard estimation equations and a pre-prepared diet will be used for education. Education will include number and size of serves of each food group and lists of 'allowed' foods. Sample meal plans will be individualised for the patient.
Control group
Active

Outcomes
Primary outcome [1] 287693 0
Percentage of hepatic steatosis as assessed using magnetic resonance spectroscopy (MRS)
Timepoint [1] 287693 0
Baseline and 12 weeks (3 months)
Secondary outcome [1] 298647 0
Severity of liver injury will be assessed using liver enzymes (ALT, AST, GGT), serum markers of hepatocyte apoptosis and necrosis (CK-18) and non-invasive assessment of hepatic fibrosis using Fibroscan and Hepascore.
Timepoint [1] 298647 0
Baseline - all assessments listed above
4 weeks - blood markers only
8 weeks - blood markers only
12 weeks - all assessments listed above
Secondary outcome [2] 298648 0
Arterial stiffness (ie. subclinical vascular disease) will be assessed using applanation tonometry (SphygmoCor TM) to measure the aortic augmentation index and pulse wave velocity
Timepoint [2] 298648 0
Baseline
12 weeks
Secondary outcome [3] 298649 0
Cardiovascular risk profile will be assessed using Framingham Risk Score
Timepoint [3] 298649 0
Baseline
12 weeks

Eligibility
Key inclusion criteria
NAFLD diagnosis with hepatic steatosis (>5.5% as determined by MRS).
Weight stability; variation of <5% within the preceding 3-month period.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Secondary causes of NAFLD.
Other causes of liver disease deficiency.
Type 2 diabetes mellitus with A1C >8.5% or requiring insulin.
Mean alcohol consumption > 20 g/day or 140 g per week in females, >30 g/day or 210 g/week in males.
Decompensated liver cirrhosis.
Renal failure.
Malignancy aside from skin cancer.
Current tobacco use.
Conditions preventing required assessment or informed consent.
Use of weight loss medications.
Lipid lowering medications.
Fish oil supplement use within the past 3 months.
Pregnancy or lactation.
Patients unwilling/unable to maintain stable body weight and/or comply with specifically prescribed dietary intake.

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)
Subjects will be recruited from existing NAFLD clinics within the clinical sites. Subjects within the clinics will be provided with patient information outlining the trial and it's general aims and asked to volunteer.
Volunteers will be assessed against the inclusion and exclusion criteria. Allocations will occur via a schedule held by the departmental research assistant (on passworded computer file) and this information will be obtained from the assistant after the researchers have determined eligibility.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will undergo all baseline measures and then allocation to a group will be via block-randomisation, with stratification for type 2 diabetes. Subjects will then be educated about their new dietary regime. All subjects will be unaware of the two dietary types and therefore will not know what type of diet they are following. To allow them to follow the regime they will be given details of the 'allowed' foods within each food group, the number of serves of the food group they will need to consume per day and per week, and the amount of the food that constitutes 'one serve'.
Investigators will be aware of the allocation in order to provide correct education and monitor compliance to the prescribed regime.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285768 0
Hospital
Name [1] 285768 0
Research fund of the Hepatology Unit at Sir Charles Gairdner Hospital
Country [1] 285768 0
Australia
Primary sponsor type
Individual
Name
Catherine Properzi
Address
Edith Cowan University
PhD Student
C/o - Building 19.129
270 Joondalup Drive
Joondalup, WA, 6027
Country
Australia
Secondary sponsor category [1] 284595 0
Individual
Name [1] 284595 0
Associate Professor Leon Adams
Address [1] 284595 0
c/o Hepatology Unit
Level 6, G Block
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands, WA, 6009
Country [1] 284595 0
Australia
Other collaborator category [1] 277002 0
Individual
Name [1] 277002 0
Dr Therese O'Sullivan
Address [1] 277002 0
Edith Cowan University
Building 19.129
270 Joondalup Drive
Joondalup WA, 6027
Country [1] 277002 0
Australia
Other collaborator category [2] 277003 0
Individual
Name [2] 277003 0
Associate Professor Jill Sherriff
Address [2] 277003 0
Curtin School of Public Health
Building 400
Kent Street
Bentley, WA, 6102
Country [2] 277003 0
Australia
Other collaborator category [3] 277004 0
Hospital
Name [3] 277004 0
Sir Charles Gairdner Hospital
Address [3] 277004 0
Hepatology Department
Hospital Ave
Nedlands, WA, 6009
Country [3] 277004 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 287778 0
Sir Charles Gairdner Hospital HREC
Ethics committee address [1] 287778 0
Ethics committee country [1] 287778 0
Date submitted for ethics approval [1] 287778 0
29/08/2012
Approval date [1] 287778 0
Ethics approval number [1] 287778 0
2012-113

Summary
Brief summary
This study will describe the usual dietary nutrient profile of a
patient group with NAFLD and associations with a range of indicators of liver disease severity and cardiovascular risk.
After a 3-month dietary intervention with a Mediterranean-style test diet vs. a low-fat control diet, the influence on measures of cardiovascular risk and liver fat, will be assessed. Patients will maintain their weight during this 3-month period to allow for assessment of the influence of diet, independently of the known effects of weight loss.
By re-examining the same markers of liver disease severity and cardiovascular risk, the effects of the intervention and control diets will provide insight into whether there is a superior nutrient profile to improve cardiovascular risks and/or liver fat in this patient group. This will also determine if there is a role dietary therapy in NAFLD for patients who are unable lose or maintain weight loss.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34545 0
Address 34545 0
Country 34545 0
Phone 34545 0
Fax 34545 0
Email 34545 0
Contact person for public queries
Name 17792 0
Catherine Properzi
Address 17792 0
c/o
ECU
19.129
270 Joondalup Drive
Joondalup, WA, 6027
Country 17792 0
Australia
Phone 17792 0
+61 407519406
Fax 17792 0
Email 17792 0
[email protected]
Contact person for scientific queries
Name 8720 0
Catherine Properzi
Address 8720 0
c/o
ECU
19.129
270 Joondalup Drive
Joondalup, WA, 6027
Country 8720 0
Australia
Phone 8720 0
+61 407519406
Fax 8720 0
Email 8720 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Properzi C, O'Sullivan TA, Sherriff JL et al. (201... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAd Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial.2018https://dx.doi.org/10.1002/hep.30076
EmbaseHow fragile are Mediterranean diet interventions? A research-on-research study of randomised controlled trials.2021https://dx.doi.org/10.1136/bmjnph-2020-000188
N.B. These documents automatically identified may not have been verified by the study sponsor.