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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] 287371 0
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 296049 0
Nonalcoholic Steatohepatitis 296050 0
Cardiovascular Disease 296051 0
Type 2 Diabetes 296052 0
Condition category
Condition code
Diet and Nutrition 296320 296320 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 296434 296434 0 0
Other metabolic disorders
Oral and Gastrointestinal 296435 296435 0 0
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] 292716 0
Lifestyle
Intervention code [2] 292808 0
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] 295973 0
Insulin Resistance as measured by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Timepoint [1] 295973 0
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] 317082 0
Hepatic Steatosis as measured by Magnetic Resonance Spectroscopy (MRS)
Timepoint [1] 317082 0
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] 317382 0
Liver Function tests as measured by blood tests - ALT, ALP, GGT
Timepoint [2] 317382 0
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] 317383 0
Inflammatory cytokine markers will measured (Leptin, Adiponectin, high sensitivity C-Reactive Protein) using serum blood analysis
Timepoint [3] 317383 0
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] 317384 0
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] 317384 0
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] 317385 0
Liver stiffness– measured via Fibroscan (Registered Trademark) and CAP (Controlled Attenuation Parameter).
Timepoint [5] 317385 0
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] 317386 0
Anthropometric measures analysed with a calibrated stand on scales.
Timepoint [6] 317386 0
The effects of the intervention on anthropometry will be assessed at 6 and 12 weeks from the beginning of the intervention.
Secondary outcome [7] 317387 0
Effects of Mediterranean Diet diet on blood pressure will be measured using sphygmomanometer
Timepoint [7] 317387 0
The effects of the intervention on blood pressure will be assessed at 12 weeks from the beginning of the intervention.
Secondary outcome [8] 317388 0
Quality of life measures via AQoL-8D and SF 36 questionnaire
Timepoint [8] 317388 0
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] 317584 0
Body composition analysis with bioelectrical impedance analysis (BIA).
Timepoint [9] 317584 0
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] 317585 0
DEXA will be offered to all participants at La Trobe University to assess changes in fat and lean muscle mass.
Timepoint [10] 317585 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
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

Funding & Sponsors
Funding source category [1] 291933 0
University
Name [1] 291933 0
La Trobe University
Address [1] 291933 0
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] 291933 0
Australia
Primary sponsor type
University
Name
La Trobe University
Address
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
Secondary sponsor category [1] 290602 0
None
Name [1] 290602 0
Address [1] 290602 0
Country [1] 290602 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293434 0
Alfred Health Research and Ethics Committee
Ethics committee address [1] 293434 0
Alfred Health, 55 Commercial Road, Prahran, Melbourne, 3181, Victoria
Ethics committee country [1] 293434 0
Australia
Date submitted for ethics approval [1] 293434 0
06/03/2014
Approval date [1] 293434 0
17/04/2014
Ethics approval number [1] 293434 0
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 59914 0
A/Prof Audrey Tierney
Address 59914 0
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 59914 0
Australia
Phone 59914 0
+61 (0) 3 9479 5253
Fax 59914 0
+61 (0) 3 9479 5768
Email 59914 0
A.Tierney@latrobe.edu.au
Contact person for public queries
Name 59915 0
A/Prof Audrey Tierney
Address 59915 0
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 59915 0
American Samoa
Phone 59915 0
+61 (0) 3 9479 5253
Fax 59915 0
+61 (0) 3 9479 5768
Email 59915 0
A.Tierney@latrobe.edu.au
Contact person for scientific queries
Name 59916 0
A/Prof Audrey Tierney
Address 59916 0
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 59916 0
Australia
Phone 59916 0
+61 (0) 3 9479 5253
Fax 59916 0
+61 (0) 3 9479 5768
Email 59916 0
A.Tierney@latrobe.edu.au

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