MRIPD#7: Magnetic Resonance Imaging-Portfolio Diet Study #7

Sponsor

Unity Health Toronto (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02078635

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), University of Toronto (Other), Laval University (Other), University of Manitoba (Other), University of British Columbia (Other)

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief Summary

Presently in Canada, 29% of deaths are due to cardiovascular disease (CVD), costing $20.9 billion annually. The investigators have, therefore, brought together an unique network of investigators at different stages in their careers with a range of disciplines (nutrition, cardiology, diabetes, imaging, physics, clinical trials, statistics, laboratory medicine, primary care, genetics, psychology, knowledge translation (KT), and epidemiology) and with international recognition , experience and connections, to undertake a multi-centre study which will test the ability of the dietary Portfolio PLUS approach over 3 years to reduce the progression of plaque build-up in the carotid artery as assessed by Magnetic Resonance Imaging (MRI) in individuals with hypercholesterolemia.

The dietary portfolio of cholesterol-lowering foods (viscous fibres, soy protein, plant sterol and nuts) which has been proven in many of their studies to be an effective cholesterol-lowering diet will be further enhanced by increased levels of monounsaturated fats (MUFA) and low glycemic index foods. Will this enhanced dietary strategy (dietary Portfolio PLUS ) reduce the progression of carotid atheromatous lesions, LDL-C and blood pressure while reducing the number of hyperlipidemic individuals requiring statins?

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Hypercholesterolemia Diabetes Metabolic Syndrome Obesity	Behavioral: Portfolio Plus Diet Behavioral: DASH-like (high fibre) dietary advice	N/A

Detailed Description

As Western populations age and as body weight increases, the need for dietary strategies to reduce Coronary Heart Disease (CHD) risk continues. The investigators are now in a position to put together a dietary approach which will be a significant advance over current dietary advice for CHD risk reduction. The investigators believe this study using imaging and functional techniques is now needed to 1) demonstrate an improvement in estimated CHD risk based on anatomical changes rather than serum risk factors. 2) encourage popular uptake and clinical use of this combination dietary strategy and 3) stimulate a larger longer term trial with CHD events.

Participants for this study will be recruited in 4 academic centres across Canada (Quebec, Toronto, Winnipeg and Vancouver). They will be in the low or moderate risk category based on the current Canadian Cardiovascular Society's (CCS) Guidelines 2012 and would normally be considered for initial treatment with lifestyle only. All participants will first be screened by ultrasound for the presence of plaque in the carotid arteries and will then be randomized to one of the 2 treatment arms: Portfolio Plus diet (test) or modified DASH diet (control), both given as routine clinical advice with follow up visits at 3-month intervals for 6 months and then twice yearly for the remainder of the 3 year trial.

Prior to starting either diet, participants will undergo screening ultrasound examination of both right and left carotids to enable selection of those individuals whose intima-media thickness would be 5-30% below the cut point considered by the Mannheim Consensus as relevant arterial thickening to ensure a relatively low risk group, yet with some measurable arterial thickening. The main outcome will be MRI assessment of maximum vessel wall volume. This assessment will be repeated at year 3. It will be emphasized at the outset that both the dietary portfolio and the DASH-like diets have been associated with benefits in terms of cholesterol reduction to provide equal encouragement for those randomized to the test and control groups. Portfolio and DASH-like dietary advice will consist of half hour individual sessions with the dietitian at baseline, 3, and 6 months and then at 6-month intervals. Prior to starting each diet, instruction will be given on achieving the dietary goals.

At follow-up visits, the participants' completed 7-day diet records will be discussed and the original advice reinforced. Every effort will be made to obtain study blood samples and carotid imaging data from all subjects at the designated times regardless of adherence to the dietary aspects of the study protocol. All subjects will be included in the intention-to-treat analysis.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

The Canada-wide Human Nutrition Trialists' Network

Actual Primary Completion Date :

Oct 7, 2014

Actual Study Completion Date :

Oct 7, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Portfolio Plus Diet Participants will be advised to follow a low glycemic index dietary portfolio. Specifically, the advice will be to limit saturated fat (to <7% of total calories and cholesterol to <200 mg/d) plus inclusion of viscous fibres, soy protein, plant sterols and nuts, 5% extra monounsaturated fat and selection of low glycemic index foods; emphasizing current recommendations for fruit and vegetable intakes (5-10 servings/d)	Behavioral: Portfolio Plus Diet Foods on the Portfolio Plus plan will contribute 9 g/1000 kcal viscous fibre as β-glucan (oats, barley, oat bran bread and soups) and psyllium (cereal), 1 g plant sterol/1000 kcal diet (in sterol margarine), 22.5 g soy protein/1000 kcal (soy burgers, dogs, links, other soy meat analogues, soy milks, yogurts and cheese) and additional sources of plant proteins from pulses (eg. lentils, chickpeas, beans, etc); and 22.5 g almonds or equivalent of other nuts/1000 kcal and increase MUFA (as olive and canola oils, avocados, nuts, margarine and salad dressings). The glycemic index will be reduced from 83 to 70 GI units (bread scale) Other Names: Dietary Portfolio of cholesterol-lowering foods Enhanced portfolio Portfolio eating plan
Active Comparator: DASH-like (high fibre) diet The DASH-like dietary advice will emphasize a diet of whole grains, low-fat dairy and current recommendations for fruit and vegetables (5-10 servings/day)	Behavioral: DASH-like (high fibre) dietary advice Dietary advice will be given to encourage intake of whole grain foods (brown rice, whole wheat breads, muffins and breakfast cereals); to reduce red meat consumption, choose low fat dairy foods and a control margarine Other Names: high fibre diet

Arm

Intervention/Treatment

Experimental: Portfolio Plus Diet

Participants will be advised to follow a low glycemic index dietary portfolio. Specifically, the advice will be to limit saturated fat (to <7% of total calories and cholesterol to <200 mg/d) plus inclusion of viscous fibres, soy protein, plant sterols and nuts, 5% extra monounsaturated fat and selection of low glycemic index foods; emphasizing current recommendations for fruit and vegetable intakes (5-10 servings/d)

Behavioral: Portfolio Plus Diet

Foods on the Portfolio Plus plan will contribute 9 g/1000 kcal viscous fibre as β-glucan (oats, barley, oat bran bread and soups) and psyllium (cereal), 1 g plant sterol/1000 kcal diet (in sterol margarine), 22.5 g soy protein/1000 kcal (soy burgers, dogs, links, other soy meat analogues, soy milks, yogurts and cheese) and additional sources of plant proteins from pulses (eg. lentils, chickpeas, beans, etc); and 22.5 g almonds or equivalent of other nuts/1000 kcal and increase MUFA (as olive and canola oils, avocados, nuts, margarine and salad dressings). The glycemic index will be reduced from 83 to 70 GI units (bread scale)

Other Names:

Dietary Portfolio of cholesterol-lowering foods

Enhanced portfolio

Portfolio eating plan

Active Comparator: DASH-like (high fibre) diet

The DASH-like dietary advice will emphasize a diet of whole grains, low-fat dairy and current recommendations for fruit and vegetables (5-10 servings/day)

Behavioral: DASH-like (high fibre) dietary advice

Dietary advice will be given to encourage intake of whole grain foods (brown rice, whole wheat breads, muffins and breakfast cereals); to reduce red meat consumption, choose low fat dairy foods and a control margarine

Other Names:

high fibre diet

Outcome Measures

Primary Outcome Measures

Change from baseline of the maximum vessel wall volume of the carotid arteries [At baseline and year 3]
Assessed by MRI

Secondary Outcome Measures

Intra-plaque hemorrhage (IPH) [At baseline and year 3]
Assessed by MRI
Intra-plaque lipid (lipid-rich necrotic core) [baseline and year 3]
Assessed by MRI
blood pressure and pulse rate [At months 0, 3, 6, 12, 18, 24, 30, 36]
initiation of statin therapy [baseline and year 3]
According to current CCS guidelines

Other Outcome Measures

LDL-cholesterol [At months, 0, 3, 6, 12, 18, 24, 30, 36]
HDL-cholesterol [months 0, 3, 6, 12, 18, 24, 30, 36]
C-reactive protein (CRP) [At months 0, 12, 24, and 36]
The Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36) [Months 0 and 36]
Survey on quality of life.
Genetic whole genome testing [month 0]
One time sample collection of buffy coat white cells for future analysis
satiety of the test and control diet [Months 0, 3, 6, 12, 18, 24, 30, 36]
Participants will assess their level of satiety on the test/control diet at each visit using a 9-point bipolar semantic scale ranging from -4 (being starved/ feeling weak and faint with hunger) to +4 (being Painfully full) with 0 being neutral (ie don't mind eating a little more or less).
Palatability of the test / control diets [Months 3, 6, 12, 18, 24, 30, and 36]
The palatability of the diet will by measured using a numerical scale of 1 to 10 (1= strongly dislike and 10 = like very much).

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eligible participants will be:

Adult males that are within 30% of their target LDL-cholesterol for the low or moderate risk category according to the 2012 Canadian Cardiovascular Society Guidelines.
Postmenopausal women that are within 30% of their target LDL-cholesterol for the low or moderate risk category according to the 2012 Canadian Cardiovascular Society Guidelines.

Participants will have the following characteristics:

BMI 25-40 kg/m2 with body weight that has remained constant (within ±2kg) over the last 3 months preceding the onset of the study.
Measurable arterial thickening at screening (carotid intima-media thickness of >1.0mm)
Plus at least 1 of the following 3 criteria:
are treated with statins
are statin intolerant
have refused statin treatment after consultation with the appropriate physician

Exclusion Criteria:

Individuals with the following conditions will be excluded:

major cardiovascular event
stroke or
myocardial infarction
Cardiac conditions that compromise normal function
mitral valve disease
heart failure
angina
familial hypercholesterolemia
secondary causes of hypercholesterolemia
hypothyroidism (unless treated and on a stable dose of L-thyroxine)
renal or liver disease
diabetes
serum triglycerides >4.5 mmol/L
uncontrolled blood pressure
major disability
disorders requiring continuous medical attention and treatment
chronic heart failure
liver disease
renal failure
cancer (except non-melanoma skin cancer--basal cell, squamous cell)
chronic infections (bacterial or viral)
chronic inflammatory diseases ( lupus, ulcerative colitis)
other autoimmune diseases (eg celiac disease or gluten sensitivity)
major surgery <6 months prior to randomization
conditions that make them unsuitable for MRI (e.g. have metal implants or are claustrophobic)
alcohol consumption >2 drinks/ day

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Healthy Heart Lipid Clinic, St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
2	Richardson Center for Functional Foods and Nutraceuticals and the St. Boniface Hospital Cardiovascular Center, University of Manitoba	Winnipeg	Manitoba	Canada	R3T 6C5
3	Risk Factor Modification Centre, St. Michael's Hospital	Toronto	Ontario	Canada	M5C 2T2
4	Institute of Nutraceuticals and Functional Foods and the Quebec Heart and Lung Institute, Laval University	Quebec City	Quebec	Canada	G1V 4G2

Sponsors and Collaborators

Unity Health Toronto
Canadian Institutes of Health Research (CIHR)
University of Toronto
Laval University
University of Manitoba
University of British Columbia

Investigators

Principal Investigator: David J Jenkins, MD, St. Michael's Hospital / University of Toronto
Study Director: Benoit Lamarche, PhD, Laval University
Study Director: Peter Jones, PhD, University of Manitoba
Study Director: Jiri Frohlich, MD, University of British Columbia