Clinical trial NCT02078635: Magnetic Resonance Imaging-Portfolio Diet Study #7
Official title: The Canada-wide Human Nutrition Trialists' Network
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Cardiovascular Diseases
Hypercholesterolemia
Diabetes
Metabolic Syndrome
Obesity
Keywords: Arterial plaque
portfolio diet
dietary modification
dietary trials
Canadian Network
knowledge synthesis and translation
Magnetic resonance imaging
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: University of Toronto
name: Laval University
name: University of Manitoba
name: University of British Columbia
First posted: 2014-03-05
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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?

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.

Eligibility criteria: Inclusion Criteria:

Eligible participants will be:

1. 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.
2. 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

Primary outcomes:
measure: Change from baseline of the maximum vessel wall volume of the carotid arteries
timeFrame: At baseline and year 3
Secondary outcomes:
measure: Intra-plaque hemorrhage (IPH)
timeFrame: At baseline and year 3
measure: Intra-plaque lipid (lipid-rich necrotic core)
timeFrame: baseline and year 3
measure: blood pressure and pulse rate
timeFrame: At months 0, 3, 6, 12, 18, 24, 30, 36
measure: initiation of statin therapy
timeFrame: baseline and year 3
Other outcomes:
measure: LDL-cholesterol
timeFrame: At months, 0, 3, 6, 12, 18, 24, 30, 36
measure: HDL-cholesterol
timeFrame: months 0, 3, 6, 12, 18, 24, 30, 36
measure: C-reactive protein (CRP)
timeFrame: At months 0, 12, 24, and 36
measure: The Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36)
timeFrame: Months 0 and 36
measure: Genetic whole genome testing
timeFrame: month 0
measure: satiety of the test and control diet
timeFrame: Months 0, 3, 6, 12, 18, 24, 30, 36
measure: Palatability of the test / control diets
timeFrame: Months 3, 6, 12, 18, 24, 30, and 36
Locations:
city: Vancouver
country: Canada
facility: Healthy Heart Lipid Clinic, St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Richardson Center for Functional Foods and Nutraceuticals and the St. Boniface Hospital Cardiovascular Center, University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Risk Factor Modification Centre, St. Michael's Hospital
state: Ontario
city: Quebec City
country: Canada
facility: Institute of Nutraceuticals and Functional Foods and the Quebec Heart and Lung Institute, Laval University
state: Quebec
Study officials:
affiliation: St. Michael's Hospital / University of Toronto
name: David J Jenkins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laval University
name: Benoit Lamarche, PhD
role: STUDY_DIRECTOR
affiliation: University of Manitoba
name: Peter Jones, PhD
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: Jiri Frohlich, MD
role: STUDY_DIRECTOR
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