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Trial registered on ANZCTR

Registration number

ACTRN12616001046493

Ethics application status

Approved

Date submitted

2/08/2016

Date registered

5/08/2016

Date last updated

21/04/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Effect of a Mediterranean diet with fresh lean Australian pork on blood pressure, cardiovascular risk factors and cognition, mood and wellbeing in high risk individuals.

Scientific title

Effect of a Mediterranean diet with fresh lean Australian pork on blood pressure, cardiovascular risk factors and cognition, mood and wellbeing in high risk individuals.

Secondary ID [1]

none

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Cardiovascular Health

Cardiometabolic Health

Wellbeing and cognitive performance

Condition category

Condition code

Diet and Nutrition

Other diet and nutrition disorders

Cardiovascular

Hypertension

Mental Health

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. Outcome measures will be recorded at the start and end of each 8 week phase (ie baseline, week8, week 16, week 24).

At baseline volunteers will meet with the dietitian, for approximately 30mintues, and received instructions regarding their dietary prescription for the next 8 weeks. Volunteers will be prescribed their allocated diet, receive recipes and their sample menu (during Mediterranean diet) 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 MedDiet phase, volunteers will receive lean fresh Australian pork plus 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 Diet (MedDiet) with pork.
The MedDiet is characterised by a variety of foods including wholegrain cereals, nuts, legumes, extra virgin olive oil, red wine, small amounts of red meat, low intakes of dairy (mainly yoghurt and cheese), fish, fruits and vegetables. The MedDiet will be based on the PREDIMED-EVOO diet as described by Estruch R et al (NEJM 2013) and fresh lean pork will be included as an alternative option for protein food.

Guidelines for following the MedDiet are adapted from Estruch R et al 2013 NEJM, include:
Abundant use of extra virgin olive oil for cooking and dressing vegetables and salads
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, cheese 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

Adherence to the MedDiet will be assessed using a 14-point adherence score assessed fortnightly. Compliance to the MedDiet will be assessed from weighed food records conducted at the beginning and end of each dietary phase and through daily checklists. All volunteers will see the dietitian fortnightly who will discuss strategies to maintain compliance to the MedDiet.

Intervention code [1]

Prevention

Intervention code [2]

Lifestyle

Comparator / control treatment

The comparator treatment is a low fat diet.

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.

Guidelines include:
Purchase low fat foods
Choosing lean cuts of meat and trimming all visible fat from meats and remove skin from chicken
Maintain habitual pork consumption
Eat fish instead of meat 2-3 times per week
Avoid processed meats including bacon, beef and lamb
Cooking with less fat avoiding use oil, butter or fat-based sauces (canola spray is recommended)
Employ low fat cooking methods
Remove excess fat from foods (i.e. skim fat from top of casseroles/stews etc.)
Use spreads sparingly
Limit take-away, fried and commercial foods
Limit consumption of nuts
Avoid, cakes, pies, pastries, chips etc.

Adherence to the LFD will be assessed using a 9-point adherence score assessed fortnightly. Compliance to the LFD will be assessed from weighed food records conducted at the beginning and end of each dietary phase. All volunteers will see the dietitian fortnightly who will discuss strategies to maintain compliance to both dietary interventions

Control group

Active

Outcomes

Primary outcome [1]

Blood pressure will be determined by automatic oscillatory using a Digital Blood Pressure Monitor. Volunteers will monitor blood pressure three times a day, at home, for 6 days generating 54 data points of blood pressure readings where the average will be taken.

Timepoint [1]

Home measured blood pressure will be measured 6 days prior to baseline, during weeks 7-8, 15-16 and 23-24.

Secondary outcome [1]

% body fat, assessed by dual X-ray absorptiometry (DEXA)

Timepoint [1]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [2]

Heart Rate, measured by automatic oscillometry.

Timepoint [2]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [3]

Body Mass Index, calculated as weight divided by height in meters squared. Weight will be measured using digital scales while volunteers are wearing minimal clothing and no shoes. Height will be measured at baseline using a wall-mounted stadiometer.

Timepoint [3]

Assessed at screenig and at baseline and 8,16 and 24 weeks.

Secondary outcome [4]

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 waits/hip circumference.

Timepoint [4]

Assessed at baseline and 8,16 and 24 weeks. Waist will be assessed at screening.

Secondary outcome [5]

Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: visual and verbal memory.

Timepoint [5]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [6]

Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: speed of processing (reaction and attention)

Timepoint [6]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [7]

Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: executive function

Timepoint [7]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [8]

Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: social cognition

Timepoint [8]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [9]

Cognitive performance will be assessed using the CANTAB 'registered trademark' computerised test battery: decision making

Timepoint [9]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [10]

Addenbrooke's Cognitive Examination Revised (ACE-R) is a brief cognitive test battery that has been validated for use to detect early cognitive dysfunction through scoring five different cognitive domains (memory, attention/orientation, fluency, language and visouspatial). (Mioshi et al 2006) This will be used at screening to rule out dementia and Alzhemier's disease and as an outcome measure as it is sensitive in detecting very mild-cognitive impairment.

Timepoint [10]

Assessed at screening, baseline and 8,16 and 24 weeks.

Secondary outcome [11]

Mood will be assessed using the Profile of Mood State (POMS) questionnaire (McNair 1971).

Timepoint [11]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [12]

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 CAIDE will be assessed in volunteers aged between 45-65 years (validated in this age range)

Timepoint [12]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [13]

Framingham Risk Score is a gender specific calculator used to estimate an individual's 10 year risk of developing cardiovasular disease.

Timepoint [13]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [14]

Physical health-related quality of life will be assessed using the Short Form Health Survey (SF36V2)

Timepoint [14]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [15]

Insulin Resistance calculated from serum insulin and glucose. Insulin resistance will be calculated using the Homeostasis Model Assessment (HOMA2) Calculator.

Timepoint [15]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [16]

Plasma C-reactive protein (inflammatory marker)

Timepoint [16]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [17]

Plasma total Cholesterol levels

Timepoint [17]

Assessed at screening then baseline and 8,16 and 24 weeks.

Secondary outcome [18]

Plasma low denstiy lipoprotein (LDL) cholesterol levels

Timepoint [18]

Assessed at screening then baseline and 8,16 and 24 weeks.

Secondary outcome [19]

Plasma high density lipoprotein (HDL) cholesterol levels

Timepoint [19]

Assessed at screening then baseline and 8,16 and 24 weeks.

Secondary outcome [20]

Plasma triglyceride levels

Timepoint [20]

Assessed at screenig then baseline and 8,16 and 24 weeks.

Secondary outcome [21]

Apolipoprotein E-4 allele (APOE4, indicator of increased risk for Alzheimer's Disease) as assessed from blood sample using the TaqMan 'registered trademark' SNP Genotyping Assay Kit (Applied Biosystems, Warrington, UK) (Koch et al 2002)

Timepoint [21]

Assessed at baseline

Secondary outcome [22]

Fat Mass (DEXA)

Timepoint [22]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [23]

Lean Mass (DEXA)

Timepoint [23]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [24]

Abdominal Body fat (DEXA)

Timepoint [24]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [25]

Faecal Microbiome profile. The omnigene GUT collection system will provide an easy non-invasive stool collection kit for volunteers to use at home.

Timepoint [25]

Assessed at baseline and 8,16 and 24 weeks.

Secondary outcome [26]

Mediterranean Dietary Adherence using the 14-point MedDiet adherence tool and weighed food records.

Timepoint [26]

Assessed at screening and then at baseline and every fortnight of the MedDiet phase (total 6 occasions).

Secondary outcome [27]

Low Fat Dietary Adherence using the 9-point low fat diet adherence tool (Estruch et al 2013).

Timepoint [27]

Baseline and every fortnight of the low fat diet phase (total 5 occasions)

Secondary outcome [28]

Plasma levels of glucose will be assessed using standard methods via venepuncture. Finger prick glucose will be taken using a lancet and measured using a glucometer at screening.

Timepoint [28]

Assessed at screening then baseline and at week 8, 16 and 24.

Secondary outcome [29]

Serum levels of insulin

Timepoint [29]

Assessed at baseline and at week 8, 16 and 24.

Secondary outcome [30]

Energy and macro and micronutrient intakes will be calculated from 6 day weighed food records entered into Foodworks Professional Software program.

Timepoint [30]

Assessed at baseline and at week 8, 16 and 24.

Secondary outcome [31]

In-clinic assessed blood pressure will be determined by automatic oscillatory using a Digital Blood Pressure Monitor. On each occasion 3 readings will be taken spaced at least 1 minute apart, and the average of the readings will be used.

Timepoint [31]

At screening, then at baseline and at weeks 8, 16 and 24.

Secondary outcome [32]

Mental health-related quality of life; will be assessed using the Short Form Health Survey (SF36V2)

Timepoint [32]

At baseline, week 8, 16 and 24.

Secondary outcome [33]

Social health-related quality of life will be assessed using the Short Form Health Survey (SF36V2)

Timepoint [33]

At baseline, week 8, 16, and 24.

Eligibility

Key inclusion criteria

Free-living non-smoking men and women, aged between 45-75 years with elevated SBP equal to or above 120mmHg (high-normal range) and not on antihypertensive medication,
who habitually consume 1 or less serves of fresh pork per week
WITH at least 2 risk factors for CVD:

1. overweight/obese with BMI equal to or above 25kg/m2
2. waist circumference men greater than94cm, women greater than 80cm
3. dyslipidemia one of the following: total cholesterol equal to or greater than 5.5mM, triglycerides equal to or greater than 2.0mM, LDL equal to or greater than 3.5, HDL men equal to or less than 0.9 women less than 1.0,
4. impaired glucose tolerance (fasted glucose between 6.1-7.8mmol/L)
5. Family history of CVD (MI or sudden death before 55yrs for men or 65yrs for female 1st degree relatives)
6. Family history of type 2 diabetes mellitus (T2DM)

Minimum age

45 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Person considered by the investigator to be unwilling, unlikely or unable to comprehend or comply with the study protocol
2. Unable to consume pork
3. Previous/current traumatic head/brain injury, neurological or psychiatric conditions
4. Previous stroke
5. Use of anti-depressant, anxiety or neurological or psychiatric medication
6. Current or recent (in the last 6 months) malignancy
7. Major liver, kidney, respiratory, gastrointestinal disease
8. Current CVD or angina
9. Actively trying to lose weight
10. Pregnancy/lactating
11. Smoker (within the last 6months)
12. Diagnosed T2DM
13. Allergy/sensitivity to nuts, seafood, etc. relevant to the dietary protocol
14. Illegal drug use or alcoholism
15. Weight >135kg (DEXA limitations)
16. Diagnosis of Alzheimer’s Disease, 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 commence the intervention.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Crossover

Other design features

Two 8-week dietary phases will be separated by an 8-week washout period where the volunteer will return to their habitual diet before commencing their crossover diet.

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 2.5mmHg reduction in blood pressure is clinically relevant. Whilst this reduction seems small for the individual, at the population level this reduction translates to a 7-8% to up to 15% risk reduction in stroke, hypertension and CVD. With a PREDIMED-nuts diet together with other dietary bioactives, we could see as much as a 4-5 mmHg reduction in blood pressure particularly in an ‘at-risk’ population.

To account for an approximate 10% drop-out rate based on our past trials, we will recruit an additional 9 volunteers. Total volunteers to be recruited is 39.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/09/2016

Actual

25/01/2017

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)

Recruitment postcode(s) [1]

5001 - Adelaide

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Pork CRC Pty Ltd

Address [1]

Po Box 466
Willaston
South Australia 5118

Country [1]

Australia

Primary sponsor type

University

Name

University of South Australia

Address

GPO Box 2471, Adelaide 5001, South Australia

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Dr Karen Murphy

Address [1]

Alliance for Research in exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia

Country [1]

Australia

Secondary sponsor category [2]

Individual

Name [2]

Prof. Jonathan Hodgson

Address [2]

Medicine and Pharmacology Royal Perth Hospital Unit, The University of Western Australia (M500), 35 Stirling Highway, Crawley, Western Australia 6009

Country [2]

Australia

Secondary sponsor category [3]

Individual

Name [3]

Dr Hannah Keage

Address [3]

School of Psychology, Social Work, and Social Policy, University of South Australia, May Wheaton Building, Level 2, H2-19, Magill Campus, GPO Box 2471, Adelaide 5001, South Australia

Country [3]

Australia

Secondary sponsor category [4]

Individual

Name [4]

Courtney Davis

Address [4]

Alliance for Research in exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia

Country [4]

Australia

Secondary sponsor category [5]

Individual

Name [5]

Alexandra Wade

Address [5]

Alliance for Research in exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia

Country [5]

Australia

Secondary sponsor category [6]

Individual

Name [6]

Prof Richard Woodman

Address [6]

Flinder University of South Australia, Flinders Centre for Epidemiology and Biostatistics, Flinders University, Adelaide, GPO Box 2100, Adelaide 5001, South Australia

Country [6]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Universtiy of south Australia Human research Ethics Committee

Ethics committee address [1]

University of South Australia
Mawson Lakes Campus, Mawson Boulevard, Mawson Lakes, SA 5095

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/06/2016

Approval date [1]

02/08/2016

Ethics approval number [1]

35662

Summary

Brief summary

The aim of this project is to determine the effect of a Mediterranean diet with lean fresh pork in comparison with a low fat diet on risk factors for CVD and cognitive function, mood and wellbeing in a randomised crossover dietary intervention trial in a population of men and women at risk of CVD.
The primary outcome is home measured blood pressure (BP).
Secondary outcomes include the Framingham heart risk score, dementia risk score, mood, wellbeing, cognitive performance (memory, executive function, speed of processing visual spatial and attention), blood lipids, insulin, glucose, insulin resistance, C Reactive Protein, erythrocyte fatty acids, apolipoprotein E4, body mass index, abdominal adiposity and body composition, weight, waist:hip ratio, gut microbiome profile, clinic blood pressure, dietary intake data and Mediterranean dietary adherence and low fat dietary adherence.

This is a randomised crossover dietary intervention trial with 39 men and women aged 45-75 years at high risk of CVD. They will be included if they have systolic blood pressure greater than 120mmHg PLUS at least two risk factors for CVD including : BMI >25kg/m2 (overweight), abdominal adiposity, impaired glucose tolerance, dyslipidemia, family history of CVD or type 2 diabetes. Half the group will be randomly allocated to commence with either a Mediterranean diet with pork (MedDiet) or a lowfat diet (control current best practice) for 8weeks, then move to a washout diet for 8 weeks (habitual diet) then move to the other diet for the remaining 8weeks.
At the start and end of each 8 week dietary phase volunteers will have all outcomes measured. 

Following an overnight fast, volunteers will attend their clinic visit and will have the following outcomes measured prior to breakfast:
Height,
weight
Waist/hip circumference
Blood pressure
40mL blood sample
DEXA scan to assess body composition
Following a light standard continental breakfast;
Cognitive performance will be measured.
Volunteers will meet with the dietitian and receive instructions regarding their dietary prescription for the next 8 weeks. They will be issued a diet checklist to ensure they are complying with the diet and receive some food staples.
During this appointment volunteers will return items that were issued to them 1 week prior;  their blood pressure monitors and 6day readings, together with their 3day weighed food record, faecal specimen and questionnaires.

All volunteers will be asked to maintain their usual exercise pattern throughout the study.. Volunteers will be asked to return fortnightly during each diet phase to see the dietitian.

Trial website

NA

Trial related presentations / publications

Nil

Public notes

Nil

Contacts

Principal investigator

Name

Dr Karen Murphy

Address

Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia

Country

Australia

Phone

+61 8 8302 1033

Fax

[email protected]

Contact person for public queries

Name

Karen Murphy

Address

Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia

Country

Australia

Phone

+61 8 83021033

Fax

[email protected]

Contact person for scientific queries

Name

Karen Murphy

Address

Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, GPO Box 2471, Adelaide 5001, South Australia

Country

Australia

Phone

+61 8 83021033

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

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Including pork in the Mediterranean diet for an Australian population: Protocol for a randomised controlled trial assessing cardiovascular risk and cognitive function.	2017	https://dx.doi.org/10.1186/s12937-017-0306-x
Embase	A mediterranean diet with fresh, lean pork improves processing speed and mood: Cognitive findings from the medpork randomised controlled trial.	2019	https://dx.doi.org/10.3390/nu11071521
Embase	Effects of Mediterranean diet supplemented with lean pork on blood pressure and markers of cardiovascular risk: Findings from the MedPork trial.	2019	https://dx.doi.org/10.1017/S0007114519001168

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

Trial Review

Documents added manually

Documents added automatically