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Trial registered on ANZCTR


Registration number
ACTRN12616000309482
Ethics application status
Approved
Date submitted
17/12/2015
Date registered
9/03/2016
Date last updated
21/04/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of a Mediterranean diet with adequate dairy foods on cardio-metabolic and cognitive health outcomes
Scientific title
The effect of a Mediterranean Diet, with adequate dairy foods, to meet Australian recommendations, on cardiometabolic and cognitive health outcomes in men and women at high risk of cardiovascular disease.
Secondary ID [1] 287793 0
no secondary ID
Universal Trial Number (UTN)
Trial acronym
MedDairy
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular health 296679 0
Cardiometabolic health 296680 0
Wellbeing and cognitive performance 296681 0
Condition category
Condition code
Diet and Nutrition 296909 296909 0 0
Other diet and nutrition disorders
Cardiovascular 296910 296910 0 0
Hypertension
Mental Health 296911 296911 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised cross-over dietary intervention trial with two 8-week dietary phases (Mediterranean diet and low fat diet) separated by an 8 week washout period. Total duration of the trial is 24 weeks.

At baseline, volunteers will meet with the dietitian, for approximately 30 minutes, and receive instructions regarding their dietary prescription for the next 8 weeks. Volunteers will be prescribed their allocated diet, receive a recipe book (The Mediterranean Diet, Catherine Itsiopoulos, Pan Macmillan Australia Pty Ltd) and a sample menu (if MedDairy group) to help guide food choices. Volunteers will be given advice on eating out strategies to assist with compliance to their allocated diet. They will be issued a diet checklist to ensure they are complying with the diet. During the MedDairy phase, volunteers will receive foods characteristic of the MedDiet (olive oil, canned fish, nuts etc.) to assist with compliance. All volunteers will be asked to maintain their usual exercise pattern. Volunteers will be asked to return fortnightly to see the dietitian (for 15-30 minutes), have their weight measured return checklists, collect study foods and discuss any problems that may have arisen during the intervention. During the washout periods between diet phases, volunteers will be asked to return to following their habitual diet.

Mediterranean DAIRY diet (MedDairy)
The MedDiet is characterised by a variety of foods including wholegrain cereals, nuts, legumes, olive oil, red wine, small amounts of red meat, low intakes of dairy (mainly yoghurt and cheese), fish, red wine, fruits and vegetables. For this study the MedDairy diet will be based on the PREDIMED-EVOO diet however volunteers will consume 3-4 serves of low-fat and regular dairy products including cheese, milk and yoghurt. To ensure we meet the Australian recommendations for dairy foods, we are recommending 3-4 serves of dairy foods per day.

Guidelines for following the MedDairy diet are adapted from Estruch R et al 2013 NEJM, include:
Abundant use of extra virgin olive oil for cooking and dressing vegetables and salad
3-4 daily servings of reduced fat milk (1 cup), yoghurt (200g) and tzatziki dip (200g), regular fat cheese (40g hard/semi-soft cheese, 120 g soft cheese)
2-3 or more daily servings of fresh fruits including 100% natural juices
3 or more weekly servings of legumes (75g per serve)
3 or more weekly servings of fish and seafood (at least one serving of oily fish) (100g per serve)
3 or more weekly serving of nuts (7.5g hazelnuts, 15g walnuts, 7.5g almonds) or seeds (30g per serve)
Ad-libitum consumption of wholegrain cereal products (bread, pasta, rice, cereal), nuts, fish, eggs and raw and cooked vegetables.
Select white meats (poultry without skin) instead of red meats or processed meats (burgers, sausages, deli meats)
Limit consumption of cured ham, red meat (remove all visible fat) to 1 or less serve/week
Remove chicken skin
Cook regularly (at least twice a week) with tomato, garlic and onion
Dress vegetables, pasta, rice and other dishes with tomato, garlic and onion
Eliminate or limit the consumption of cream, butter, margarine and discretionary foods

Low-fat diet (LFD)
The LFD will be based on the PREDIMED control diet (Estruch R et al 2013 NEJM) following American Heart Association in combination with local recommendations for the Heart Foundation of Australia. Volunteers will maintain the basis of their habitual diet however will be asked to modify their intake to choose low fat foods. Specifically : cook with little fat, remove / skim fats from foods, choose and purchase low fat foods
Intervention code [1] 293191 0
Prevention
Intervention code [2] 293192 0
Lifestyle
Comparator / control treatment
The comparator treatment is a low fat diet.
Control group
Active

Outcomes
Primary outcome [1] 296517 0
Blood pressure will be determined by automatic oscillatory using a Digital Blood Pressure Monitor (UA-767PC). Blood pressure will be measured at each clinic visit by staff. On each occasion 4 readings will be taken, spaced 3 minutes apart. The first reading will be discarded and the mean of the 3 readings will be recorded. Volunteers will also monitor blood pressure twice daily at home for 6 days. Blood pressure will be measured every day for 1 week, immediately after waking, and before going to bed. On each occasion 4 readings will be taken, spaced 3 minutes apart. The first reading is discarded and the mean of the next 3 readings is taken.
Timepoint [1] 296517 0
Clinic measured blood pressure will be assessed at baseline and 8, 16 and 24 weeks.
Home measured blood pressure will be measured 6 days prior to baseline, during weeks 7-8, 15-16 and 23-24.
Secondary outcome [1] 318645 0
% body fat, assessed by dual Energy X-ray absorptiometry (DEXA)
Timepoint [1] 318645 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [2] 318649 0
The fecal microbiome will be collected using the Omnigene GUT collection system. Volunteers will defecate in a plastic take-away container and then using the kit will sample a small amount of the stool, place it in the tube provided, screw the cap onto the tube and store in the collection envelope until delivered to the clinical trials facility. This is an easy non-invasive process.
Timepoint [2] 318649 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [3] 318652 0
Mood will be assessed using the Profile of Mood State (POMS) questionnaire (McNair 1971) which contains 65 words/statements that describe feelings people have in the past week including current day. .
Timepoint [3] 318652 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [4] 318653 0
Addenbrooke’s Cognitive Examination Revised (ACE-R):
The ACE-R is a brief cognitive test battery that has been validated for use to detect early cognitive dysfunction through scoring five difference cognitive domains (memory, attention/orientation, fluency, language and visuospatial). The maximum score is 100 (higher score reflects better cognitive performance) (Mioshi et al. 2006). This will be used at screening to rule out dementia and Alzheimer’s disease and as an outcome measure as it is sensitive in detecting very mild-cognitive impairment.
Timepoint [4] 318653 0
Assessed at screening, baseline and 8, 16 and 24 weeks.
Secondary outcome [5] 318654 0
Waist and hip circumference (in centimeters) will be measured according to the ISAK International Standards for Anthropometric Assessment. Waist/hip ratio will be calculated by dividing waist/hip circumference.
Timepoint [5] 318654 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [6] 318665 0
Insulin resistance calculated from serum insulin and glucose. Insulin resistance will be calculated using The Homeostasis Model Assessment (HOMA2) Calculator
Timepoint [6] 318665 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [7] 318666 0
Plasma C-reactive protein (inflammatory marker)
Timepoint [7] 318666 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [8] 319625 0
Mediterranean dietary adherence using 14-point MedDiet tool and weighed food records
Timepoint [8] 319625 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [9] 319626 0
The CAIDE Dementia Risk Score was developed to identify individuals at increased risk for developing dementia (20 years later) based on midlife presence of metabolic and vascular risk factors that would potentially benefit from preventative interventions to reduce their risk (Sindi 2015). The validated risk score is based on multifactorial risk estimation using age, education level, obesity, hypertension, hypercholesterolemia and physical inactivity. Normal risk of dementia is considered a score of 8-9, above normal risk for developing dementia is 10-15 and below normal risk is 0-7. The CAIDE will be assessed in volunteers aged between 45-65 years (validated in this age range).
Timepoint [9] 319626 0
Assessed at baseline and 8, 16 and 24 weeks
Secondary outcome [10] 319627 0
Framingham Risk Score is a gender specific calculator used to estimate an individual’s 10 year risk of developing CVD. The score is based on age/age range, gender, total cholesterol, dyslipidemia, blood pressure hypertension treatment and smoking and diabetes/impaired glucose tolerance. The FRS provides an indication of the possible benefits of prevention which is important for healthcare professionals in tailoring medical and dietetic advice. Individuals with low risk of having CVD in 10 years is 10% or less; intermediate risk is 10-20%, and high risk is 20% or more
Timepoint [10] 319627 0
Assessed at baseline and 8, 16 and 24 weeks.
Secondary outcome [11] 321439 0
ApoE4
A blood sample for Apolipoprotein E-4 allele (APOE4, indicator of increased risk for Alzheimer’s Disease) will be taken and analysed using the TaqMan "registered trademark' SNP Genotyping Assay kit (Applied Biosystems, Warrington, UK) (Koch et al. 2002).
Timepoint [11] 321439 0
Assessed at baseline
Secondary outcome [12] 321440 0
Body mass index, calculated as weight divided by height in metres squared. Weight will be measured using the same set of digital scales, while volunteers are wearing light clothing and no shoes. Height will be measured at time point zero only using a wall-mounted stadiometer (SECA, Hamburg, Germany) with volunteers in stockinged or bare feet.
Timepoint [12] 321440 0
Assessed at baseline, 8, 16 and 24 weeks
Secondary outcome [13] 321441 0
Heart rate, measured by automatic oscillometry while seated
Timepoint [13] 321441 0
Assessed at baseline, 8, 16, 24 weeks
Secondary outcome [14] 321442 0
Clinic measured blood pressure, measured by automatic oscillometry while seated
Timepoint [14] 321442 0
Assessed at baseline, 8, 16, 24 weeks
Secondary outcome [15] 321443 0
Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: visual and verbal memory
Timepoint [15] 321443 0
Assessed at baseline, 8, 16 and 24 weeks
Secondary outcome [16] 321444 0
Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: speed of processing (reaction and attention)
Timepoint [16] 321444 0
Assessed at baseline, 8, 16 and 24 weeks
Secondary outcome [17] 321445 0
Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: executive function
Timepoint [17] 321445 0
Assessed at baseline, 8, 16 and 24 weeks
Secondary outcome [18] 321446 0
Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: social cognition
Timepoint [18] 321446 0
Assessed at baseline, 8, 16 and 24 weeks
Secondary outcome [19] 321447 0
Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: decision making
Timepoint [19] 321447 0
Assessed at baseline, 8, 16 and 24 weeks
Secondary outcome [20] 321503 0
Lean body mass (DEXA)
Timepoint [20] 321503 0
0,8,16, 24 weeks
Secondary outcome [21] 321504 0
Abdominal body fat (DEXA)
Timepoint [21] 321504 0
0,8,16, 24 weeks
Secondary outcome [22] 321505 0
Fat mass (DEXA)
Timepoint [22] 321505 0
0,8,16, 24 weeks
Secondary outcome [23] 321506 0
Plasma total cholesterol
Timepoint [23] 321506 0
0,8,16, 24 weeks
Secondary outcome [24] 321507 0
Plasma low density lipoprotein cholesterol
Timepoint [24] 321507 0
0,8,16, 24 weeks
Secondary outcome [25] 321508 0
Plasma high density lipoprotein cholesterol
Timepoint [25] 321508 0
0,8,16, 24 weeks
Secondary outcome [26] 321509 0
Plasma triglcyerides
Timepoint [26] 321509 0
0,8,16, 24 weeks
Secondary outcome [27] 321510 0
Well-being will be focussed on health related quality of life based on outcomes reported by PREDIMED investigators (Henriquez Sanchez et al. 2012; Ruano et al. 2013) - Physical health-related quality of life will be assessed using the Short Form Health Survey (SF-36V2).
Timepoint [27] 321510 0
Baseline, 8, 16, 24 weeks
Secondary outcome [28] 321511 0
Well-being will be focussed on health related quality of life based on outcomes reported by PREDIMED investigators (Henriquez Sanchez et al. 2012; Ruano et al. 2013)- mental related quality of life will be assessed using the Short Form Health Survey (SF-36V2).
Timepoint [28] 321511 0
Baseline, 8, 16, 24 weeks
Secondary outcome [29] 321512 0
Well-being will be focussed on health related quality of life based on outcomes reported by PREDIMED investigators (Henriquez Sanchez et al. 2012; Ruano et al. 2013)- social health-related quality of life will be assessed using the Short Form Health Survey (SF-36V2).
Timepoint [29] 321512 0
Baseline, 8, 16, 24 weeks
Secondary outcome [30] 321513 0
Mood state will be assessed using the Profile of Mood State Questionnaire (POMS)
Timepoint [30] 321513 0
Baseline, 8, 16, 24 weeks

Eligibility
Key inclusion criteria
Free-living non-smoking men and women aged between 45 to 75 years with elevated systolic BP between 120mmHg and 140mmHg (high-normal range) and not on antihypertensive medication
with at least 2 risk factors for cardiovascular disease (CVD):
overweight/obese with body mass index 25kg/m2 or above
waist circumference men >94cm, women >80cm
dyslipidemia one of the following (fasted) : total cholesterol 5.5mM or above, triglycerides 2.0mM or above, low density lipoprotein cholesterol (LDL) 3.5 or above, high density lipoprotein cholesterol (HDL) men 0.9 and women 1.0 or below,
impaired glucose tolerance (fasting glucose <7.0mmol/L)
family history of CVD (myocardial infarction or sudden death before 55yrs for men or 65yrs for female 1st degree relatives)
Family history of type 2 diabetes mellitus (T2DM)
Minimum age
45 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Person considered by the investigator to be unwilling, unlikely or unable to comprehend or comply with the study protocol
Previous/current traumatic head/brain injury, neurological or psychiatric conditions
Previous stroke
Use of anti-depressant, anxiety or neurological or psychiatric medication
Current or recent (in the last 6 months) malignancy
Major liver, kidney, respiratory, gastrointestinal disease
Current CVD or angina
Actively trying to lose weight
Pregnancy/lactating
Smoker
Diagnosed T2DM
Allergy/sensitivity to nuts, seafood, dairy foods etc.
Illegal drug use or alcoholism
Weight >135kg (DEXA limitations)
Diagnosis of Alzheimer’s disease or dementia

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An independent holder of the randomisation schedule who will have no contact with the volunteers or be involved in data analysis, will perform treatment allocation .
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Volunteers who meet eligibility criteria will be stratified according to gender and age
and randomly allocated (by a process of minimisation) to one of two dietary
groups to start the intervention.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Nil
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
One-way ANOVA and Chi square will be used to compare baseline demographic, cardiometabolic, cognitive, wellbeing and dietary characteristics between those who completed the study and those who withdrew. Mixed effects models will be used to assess the effects of treatment, and possible carryover or period effects for each of the outcomes separately. Carry over effects will be assessed by comparing baseline values within each group between the two periods using a Group X Period interaction term in multilevel analysis. Treatment-period effects will be explored by comparing the treatment effects using a treatment X period interaction term in multilevel analysis. We will also assess possible seasonal effects by including a term for treatment X season interaction in a secondary analysis with season coded as a binary variable for Autumn or spring versus Winter or Summer.

Diet x Period X Energy intake interaction terms will be used to determine whether there are any changes in diet (total energy, macronutrient intakes) between the two diet phases. All statistical analyses will be conducted using SPSS for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA) and Stata (version 14, Statacorp, College Station, Texas). Data will be presented as means ± standard deviation (SD) for descriptives and as means+/- standard error (SEM) for reporting estimated effects. P < 0.05 is deemed significance.

A sample size of 30 participants has been calculated on the primary outcome of blood pressure assessed as home blood pressure. 30 volunteers will provide >90% power to detect a 2.5 mmHg difference in mean home systolic blood pressure assuming a within-group SD of 14 mm Hg based on our previous studies, a correlation between hourly measures of 0.6, a correlation between mean home systolic blood pressures at each time point of 0.6, and a minimum of 50 blood pressure measurements per volunteer. This calculation is based on a between group comparison of means using a type I error rate of 0.017. A total of 39 volunteers will be recruited to allow for approximate 10% drop out rate.

Recruitment
Recruitment status
Completed
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)
SA
Recruitment postcode(s) [1] 12179 0
5001 - Adelaide

Funding & Sponsors
Funding source category [1] 292326 0
Commercial sector/Industry
Name [1] 292326 0
Dairy Australia
Address [1] 292326 0
Level 5 IBM Centre, 60 City Road, Southbank, Victoria 3006

Country [1] 292326 0
Australia
Primary sponsor type
Individual
Name
Dr Karen Murphy
Address
Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide, South Australia
Country
Australia
Secondary sponsor category [1] 291001 0
Individual
Name [1] 291001 0
Prof Jonathan Hodgson
Address [1] 291001 0
Medicine and Pharmacology Royal Perth Hospital Unit, The University of Western Australia (M500), 35 Stirling Highway, Crawley, Western Australia 6009
Country [1] 291001 0
Australia
Secondary sponsor category [2] 291008 0
Individual
Name [2] 291008 0
Prof Richard Woodman
Address [2] 291008 0
Flinders University of South Australia, Flinders Centre for Epidemiology and Biostatistics, Flinders University, Adelaide, GPO Box 2100, Adelaide 5001, South Australia
Country [2] 291008 0
Australia
Secondary sponsor category [3] 291009 0
Individual
Name [3] 291009 0
Courtney Davis
Address [3] 291009 0
Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia
Country [3] 291009 0
Australia
Secondary sponsor category [4] 291816 0
Individual
Name [4] 291816 0
Dr Hannah Keage
Address [4] 291816 0
School of Psychology, Social Work and Social Policy, University of South Australia, Amy Wheaton Building, Level 2, H2-19, Magill Campus, GPO Box 2471, Adelaide 5001, South Australia
Country [4] 291816 0
Australia
Secondary sponsor category [5] 291817 0
Individual
Name [5] 291817 0
Alexandra Wade
Address [5] 291817 0
Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia
Country [5] 291817 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293793 0
University of South Australia Human Research Ethics Committee
Ethics committee address [1] 293793 0
University of South Australia
Mawson Lakes Campus, Mawson Lakes Boulevard
Mawson Lakes, SA 5095
Ethics committee country [1] 293793 0
Australia
Date submitted for ethics approval [1] 293793 0
27/10/2015
Approval date [1] 293793 0
17/12/2015
Ethics approval number [1] 293793 0
34954

Summary
Brief summary
In a crossover study, we aim to determine whether a Mediterranean diet with adequate dairy foods, consumed over 8 weeks, will improve measures of blood pressure, cardiometablic health, wellbeing and cognitive performance, more than a low fat diet in an high risk population of men and women with for cardiovascular disease (CVD). We believe that volunteers consuming a Mediterranean diet enriched with dairy foods (MedDairy diet), to meet the nutrient reference values for calcium in Australia, will have greater improvements in blood pressure than a low fat diet, based on Heart Foundation recommendations. Low fat diets are recommended for treatment of many chronic diseases such as type 2 diabetes mellitus, heart health and secondary prevention of stroke etc. together with regular physical activity. We know that the MedDiet, rich in bioactive foods and nutrients, has significant effects on longevity as well as reduced total death and death from CVD. Furthermore, given the independent reported health benefits of dairy foods on CVD risk factors including blood pressure, blood lipids etc. a diet combing both a Mediterranean diet and dairy foods (MedDairy diet) may in fact improve indices of cardiovascular health more than a low fat diet.

Trial website
NA
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 61338 0
Dr Karen Murphy
Address 61338 0
Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia
Country 61338 0
Australia
Phone 61338 0
+61 8 8302 2097
Fax 61338 0
Email 61338 0
karen.murphy@unisa.edu.au
Contact person for public queries
Name 61339 0
Dr Karen Murphy
Address 61339 0
Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia
Country 61339 0
Australia
Phone 61339 0
61 8 8302 2097
Fax 61339 0
Email 61339 0
karen.murphy@unisa.edu.au
Contact person for scientific queries
Name 61340 0
Dr Karen Murphy
Address 61340 0
Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia
Country 61340 0
Australia
Phone 61340 0
61 8 8302 2097
Fax 61340 0
Email 61340 0
karen.murphy@unisa.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary