ANZCTR - Registration

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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]

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

Presence of cardiovascular risk factors

Condition category

Condition code

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Cardiovascular

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]

Treatment: Other

Intervention code [2]

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]

Percentage of hepatic steatosis as assessed using magnetic resonance spectroscopy (MRS)

Timepoint [1]

Baseline and 12 weeks (3 months)

Secondary outcome [1]

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]

Baseline - all assessments listed above
4 weeks - blood markers only
8 weeks - blood markers only
12 weeks - all assessments listed above

Secondary outcome [2]

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]

Baseline
12 weeks

Secondary outcome [3]

Cardiovascular risk profile will be assessed using Framingham Risk Score

Timepoint [3]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Research fund of the Hepatology Unit at Sir Charles Gairdner Hospital

Address [1]

Level 6, G Block
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands, WA, 6009

Country [1]

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]

Individual

Name [1]

Associate Professor Leon Adams

Address [1]

c/o Hepatology Unit
Level 6, G Block
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands, WA, 6009

Country [1]

Australia

Other collaborator category [1]

Individual

Name [1]

Dr Therese O'Sullivan

Address [1]

Edith Cowan University
Building 19.129
270 Joondalup Drive
Joondalup WA, 6027

Country [1]

Australia

Other collaborator category [2]

Individual

Name [2]

Associate Professor Jill Sherriff

Address [2]

Curtin School of Public Health
Building 400
Kent Street
Bentley, WA, 6102

Country [2]

Australia

Other collaborator category [3]

Hospital

Name [3]

Sir Charles Gairdner Hospital

Address [3]

Hepatology Department
Hospital Ave
Nedlands, WA, 6009

Country [3]

Australia

Ethics approval

Ethics application status

Not yet submitted

Ethics committee name [1]

Sir Charles Gairdner Hospital HREC

Ethics committee address [1]

Ethics committee country [1]

Date submitted for ethics approval [1]

29/08/2012

Approval date [1]

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Catherine Properzi

Address

c/o
ECU
19.129
270 Joondalup Drive
Joondalup, WA, 6027

Country

Australia

Phone

+61 407519406

Fax

[email protected]

Contact person for scientific queries

Name

Catherine Properzi

Address

c/o
ECU
19.129
270 Joondalup Drive
Joondalup, WA, 6027

Country

Australia

Phone

+61 407519406

Fax

[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

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Properzi C, O'Sullivan TA, Sherriff JL et al. (201... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial.	2018	https://dx.doi.org/10.1002/hep.30076
Embase	How fragile are Mediterranean diet interventions? A research-on-research study of randomised controlled trials.	2021	https://dx.doi.org/10.1136/bmjnph-2020-000188

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically