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Trial registered on ANZCTR

Registration number

ACTRN12615001010583

Ethics application status

Approved

Date submitted

29/08/2015

Date registered

28/09/2015

Date last updated

22/09/2016

Type of registration

Retrospectively registered

Titles & IDs

Public title

MEDINA: Mediterranean Dietary Intervention Study in Nonalcoholic Fatty Liver Disease (NAFLD) patients

Scientific title

The effects of a Mediterranean Dietary Intervention on insulin resistance and hepatic steatosis in patients with Nonalcoholic Fatty Liver Disease (NAFLD).

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

MEDINA

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Non Alcoholic Fatty Liver Disease

Nonalcoholic Steatohepatitis

Cardiovascular Disease

Type 2 Diabetes

Condition category

Condition code

Diet and Nutrition

Other diet and nutrition disorders

Metabolic and Endocrine

Other metabolic disorders

Oral and Gastrointestinal

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

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Mediterranean Dietary Intervention versus standard diet.
This involves randomizing patients to either a Mediterranean Diet intervention arm versus a standard diet (low fat, moderate Carbohydrate) intervention. An Accredited Practicing Dietitian (APD) will provide a dietary consult for intervention patients to follow a Med Diet protocol or patients following a standard protocol (low fat, Australian Guide to Healthy Eating). A food hamper representing typical Mediterranean Diet foods (for example olive oil, nuts, natural Greek yoghurt, legumes) will be provided to the intervention group and a supermarket voucher will be provided for the standard group to purchase low fat, moderate carbohydrate food products to achieve the dietary goals. These will be provided at baseline, 6 weeks and 12 weeks.
Meal plans and recipe books are all provided at baseline to the relevant diet group. The intervention will be run over a 12 week period with a further 6 and 12month follow up to assess duration of effect and feasibility of sustaining the diet.
The dietary intervention and standard diet consults will be delivered by an APD through a face-to-face consultation initially and face-to-face consultations at mid-intervention (6 weeks) and post-intervention timepoints. There are regular phone call reviews to check dietary compliance at weeks 2, 4 and 9.
A dietitian will administer the intervention and to monitor adherence food diaries, food frequency questionnaire, plasma fatty acids and urinary hydroxytyrosol will be used as measures for compliance.

Intervention code [1]

Lifestyle

Intervention code [2]

Treatment: Other

Comparator / control treatment

The standard diet is modeled on the Australian Guide to Healthy Eating and the Heart Foundation's Guidelines of a low fat, moderate carbohydrate diet.

Control group

Active

Outcomes

Primary outcome [1]

Insulin Resistance as measured by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

Timepoint [1]

The effects of the intervention on insulin resistance will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [1]

Hepatic Steatosis as measured by Magnetic Resonance Spectroscopy (MRS)

Timepoint [1]

The effects of the intervention on hepatic steatosis will be assessed at 12 weeks from the beginning of the intervention.
Please note, this measure will not be assessed at 6 weeks due to cost of MRS, therefore we will measure at baseline and end-intervention.

Secondary outcome [2]

Liver Function tests as measured by blood tests - ALT, ALP, GGT

Timepoint [2]

The effects of the intervention on liver function will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [3]

Inflammatory cytokine markers will measured (Leptin, Adiponectin, high sensitivity C-Reactive Protein) using serum blood analysis

Timepoint [3]

The effects of the intervention on inflammatory cytokines will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [4]

Number of participants that exhibit an improvement in lipid profile by 20% from baseline - assessing total cholesterol, LDL, HDL, Triglycerides from serum levels in blood OR lipid profile - assessing total cholesterol, LDL, HDL, Triglycerides from serum levels in blood.

Timepoint [4]

The effects of the intervention on blood lipid levels will be assessed at 6 weeks and 12 weeks from the beginning of the intervention.

Secondary outcome [5]

Liver stiffness– measured via Fibroscan (Registered Trademark) and CAP (Controlled Attenuation Parameter).

Timepoint [5]

The effects of the intervention on liver stiffness will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [6]

Anthropometric measures analysed with a calibrated stand on scales.

Timepoint [6]

The effects of the intervention on anthropometry will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [7]

Effects of Mediterranean Diet diet on blood pressure will be measured using sphygmomanometer

Timepoint [7]

The effects of the intervention on blood pressure will be assessed at 12 weeks from the beginning of the intervention.

Secondary outcome [8]

Quality of life measures via AQoL-8D and SF 36 questionnaire

Timepoint [8]

The effects of the intervention on quality of life will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [9]

Body composition analysis with bioelectrical impedance analysis (BIA).

Timepoint [9]

The effects of the intervention on body composition as measured by BIA will be assessed at 6 and 12 weeks from the beginning of the intervention.

Secondary outcome [10]

DEXA will be offered to all participants at La Trobe University to assess changes in fat and lean muscle mass.

Timepoint [10]

The effects of the intervention on body composition as measured by DEXA will be assessed at 12 weeks (post intervention) from the beginning of the intervention and compared to pre-intervention DEXA.

Eligibility

Key inclusion criteria

Participants will be included if they are >18years, BMI 20-40kg/m2, Patients must have had at least one elevated serum aminotransferase (ALT) level (>20U/L female,
>30 U/L male) during the past 6 months and at screening have a level between >1.5 and <5 times Upper Limit of Normal (ULN) in the absence of another cause of liver disease. Diagnosis of NAFLD upon u/s.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Participants will be excluded if: they are non-English speaking; refusal or inability to give informed consent; average weekly alcohol ingestion >140g males or females; a current or past history of cardiovascular, cerebrovascular or peripheral vascular disease; presence of clinically relevant pulmonary, gastro-intestinal, renal, haematological, neurological, psychiatric, systemic or any acute infectious disease or signs of acute illness; Women who are pregnant or currently breastfeeding; Psychosocial or gastrointestinal (malabsorptive conditions e.g. coeliac disease) contraindications included bulimia nervosa, substance abuse, clinically significant depression, or current psychiatric care. Recent (within 3months of screening visit) change in dose/regimen or introduction of Vitamin E, Vitamin C or high dose Vitamin D, fish oil or probiotics. Participation in any other clinical study targeting diet and lifestyle factors.

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)

Participants who consent to participate in the study will be randomised (using a computer generated stratified approach generated by a statistician) into the MD (intervention) group or the standard care (control) group. The person determining the subjects eligbility was not involved in the computer generation of stratification and randomization.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Stratified allocation based on gender, presence of diabetes and cirrhosis

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Intention-to-treat (ITT) will be used to analyse the primary and secondary endpoints. Kaplan-Meier (K-M) plots and Cox’s proportional hazard models will be used to analyse and compare rates of events between control and treatment groups. Proportional hazard assumptions will be examined to ensure the validity of the conclusion drawn. For quantitative endpoints (e.g., HOMA-IR), t-test and linear regression will be used to compare the two groups. If normality assumption is not fulfilled, non-parametric tests such as Wilcoxon rank-sum (Mann-Whitney) test will be used instead. All statistical analyses will be performed using 5% significance levels. When multiple hypothesis testings are performed (e.g. with SNP data), Bonferroni correction will be used to adjust the significance levels.
Power & Sample size: The sample size has been powered to observe a change in insulin resistance as defined by HOMA-IR of 1.0 unit in the 12 week intervention period. With an 80% significance to p<0.05, we aim to recruit 47 participants per arm (94 in total) allowing for a 20% drop out rate. We envisage that to recruit this number of participants will take 24 months.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

10/03/2015

Actual

14/04/2015

Date of last participant enrolment

Anticipated

11/04/2017

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

University

Name [1]

La Trobe University

Address [1]

Discipline of Dietetics and Human Nutrition
Department of Rehabilitation, Nutrition and Sport
School of Allied Health
College of Science, Health and Engineering
La Trobe University
Bundoora
Victoria 3086

Country [1]

Australia

Primary sponsor type

University

Name

La Trobe University

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Health Research and Ethics Committee

Ethics committee address [1]

Alfred Health, 55 Commercial Road, Prahran, Melbourne, 3181, Victoria

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/03/2014

Approval date [1]

17/04/2014

Ethics approval number [1]

76/14

Summary

Brief summary

The aim of this study is to determine if the Mediterranean Diet (MD) compared to standard care (low fat diet), can reduce the severity of NAFLD and other symptoms often associated with NAFLD namely the Metabolic Syndrome (MetS). The components of the MetS which this study aims to monitor and potentially reduce includes: high blood pressure, increased waist circumference, elevated triglycerides (bad fats in the blood), reduced HDL cholesterol (good fats in the blood) and elevated glucose levels. These symptoms are referred to as the Metabolic Syndrome (MS).

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Audrey Tierney

Address

Health Sciences Building 3, Room 438
Discipline of Dietetics and Human Nutrition
Department of Rehabilitation, Nutrition and Sport
School of Allied Health
College of Science, Health and Engineering
La Trobe University
Bundoora
Victoria 3086

Country

Australia

Phone

+61 (0) 3 9479 5253

Fax

+61 (0) 3 9479 5768

[email protected]

Contact person for public queries

Name

Audrey Tierney

Address

Country

American Samoa

Phone

+61 (0) 3 9479 5253

Fax

+61 (0) 3 9479 5768

[email protected]

Contact person for scientific queries

Name

Audrey Tierney

Address

Country

Australia

Phone

+61 (0) 3 9479 5253

Fax

+61 (0) 3 9479 5768

[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
Plain language summary	No		Not analysed as yet

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Non Alcoholic Fatty Liver Disease (MEDINA): Study protocol.	2016	https://dx.doi.org/10.1186/s12876-016-0426-3
Embase	Impact of a Mediterranean diet on hepatic and metabolic outcomes in non-alcoholic fatty liver disease: The MEDINA randomised controlled trial.	2022	https://dx.doi.org/10.1111/liv.15264
Embase	Adherence to a Mediterranean diet may improve serum adiponectin in adults with nonalcoholic fatty liver disease: The MEDINA randomized controlled trial.	2023	https://dx.doi.org/10.1016/j.nutres.2023.09.005

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

Trial Review

Documents added manually

Documents added automatically