Canola Oil Multi-Centre Intervention Trial II

Study Overview
=================
Brief Summary
-----------------
The objectives of the study are to examine the health benefits of dietary canola oils on body composition, specifically on android fat, and weight management. COMIT II will also include analysis of FAEs to elucidate the mechanisms by which canola oil may be modifying body composition. Measurement of endothelial function, inflammatory, adiposity, and insulin sensitivity biomarkers will be done to determine the positive health impact of the changes in body composition achieved through canola oil consumption.

Detailed Description
-----------------
The proposed multi-center clinical trial would engage the same collaborative team that successfully operationalized COMIT I, namely, the Richardson Centre for Functional Foods and Nutraceuticals (RCFFN) at the University of Manitoba (Winnipeg, Manitoba, Canada), the L'Institut Des Nutraceutiques et des Aliments Fonctionnels (INAF) at Laval University (Quebec City, Quebec, Canada), the Department of Nutritional Sciences at The Pennsylvania State University (University Park, Pennsylvania, USA), the Risk Factor Modification Centre at St. Michael's Hospital (Toronto, Ontario, Canada). St. Boniface Hospital Research (Winnipeg, Manitoba, Canada) will be an additional clinical trial site. The proposed COMIT II research program will proceed as a double blind, randomized crossover study consisting of three treatment phases of six weeks, each separated by a 6-week washout period. Participants will consume a fixed composition of a precisely controlled basal, weight-maintaining diet (35% energy from fat, 50% carbohydrate and 15% protein) supplemented with the following treatment oils: (a) regular canola oil, (b) high stability/ high oleic canola oil and (c) a typical Western diet fat intake as a control treatment comprised largely of saturated fat with substantial levels of omega-6 linoleic acid, common to current North American intakes. Treatment oils will be isocalorically incorporated into fruit smoothies made with milk and consumed at breakfast and supper. The clinical segment of COMIT II is expected to be completed by the mid to end of the second year, with sample analyses to be completed by the end of year three.

Official Title
-----------------
Effects of Oleic Acid Enriched and Regular Canola Oil on Body Composition and Lipid Metabolism in Participants With Metabolic Syndrome

Conditions
-----------------
Cardiovascular Disease, Diabetes, Metabolic Syndrome

Intervention / Treatment
-----------------
* Other: Regular Canola Oil
* Other: High Oleic Canola Oil
* Other: Western Type Diet - Common Dietary Oils


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Waist circumference ≥94 cm for men and ≥80 cm for women Participants must meet at least one of the following secondary inclusion criteria: Fasting blood glucose of ≥ 5.6 mmol/L Triglycerides (TG) ≥1.7 mmol/L HDL cholesterol (HDL) <1 mmol/L (males) or <1.3 mmol/L (females) Blood pressure ≥130 mmHg (systolic) and/or ≥85 mmHg (diastolic). Exclusion Criteria: Kidney, or liver disease, or unstable thyroid disease Diabetes mellitus Smokers Those consuming >1 alcoholic beverage a day for women and >2 for men. Any participant taking medication known to affect lipid metabolism or endothelial function

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regular Canola Oil<br>60% oleic acid | Other: Regular Canola Oil<br> <br> |
| Experimental: High Oleic Canola Oil<br>70% oleic acid | Other: High Oleic Canola Oil<br> <br> |
| Active Comparator: Western Type Diet - Common Dietary Oils<br>Ghee, Safflower oil, Coconut oil, & flax oil | Other: Western Type Diet - Common Dietary Oils<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal imaging of visceral and subcutaneous abdominal fat | Using a Dual Energy X-Ray Absorptiometry machine to analyze body composition, including measuring visceral adiposity. Units (fat mass) measured are cm3 and lbs. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of fatty acid ethanolamides and precursors | Analysis of FAEs in the blood after consumption of treatment oils. UPLC-MS/MS will be used for FAE measurement. | 6 weeks | 
| Total lipid profiles including total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglyceride, and free fatty acid levels | Analysis of blood levels after consumption of treatment oils. Abbott Spectrum CCX Analyzer utilizing enzymatic reagents will be used to analyzed these measurements. | 6 weeks | 
| Plasma insulin level | Assessment of the change in insulin levels after consumption of treatment oils. This measurement will be analyzed by commercially available ELISA kits | 6 weeks | 
| Plasma glucose level | Assessment of changes in fasting glucose levels after consumption of treatment oils. This measurement will be analyzed by Abbott Spectrum CCX Analyzer | 6 weeks | 
| Plasma C-reactive protein level | Analysis of inflammatory marker levels after consumption of treatment oils will be conducted by ELISA kits | 6 weeks | 
| Plasma cytokines level | Analysis of inflammatory marker levels after consumption of treatment oils will be conducted by ELISA kits | 6 weeks | 
| Plant sterols and precursors of cholesterol | Analysis of plasma levels after consumption of treatment oils as indicators of cholesterol absorption and synthesis. These analysis will be conducted by gas chromatography | 6 weeks | 
| Proprotein convertase subtilisin/kexin type 9 (PCSK9) | PCSK9 will be measured as a surrogate marker of bile acid synthesis via Ultra Performance Liquid Chromatography-MS/MS | 6 weeks | 
| Endothelial function | Assessment of arterial wall resistance and arterial elasticity after consumption of treatment oils It will be assessed using flow mediated dilation | 6 weeks | 
| Fatty acid synthesis rates i.e. monounsaturated fatty acids and long chain polyunsaturated fatty acids | Heavy water enrichment of each fatty acid methyl ester after consumption of treatment oils will be measured using a gas chromatography with combustion isotope-ratio mass spectrometry | 6 weeks | 
| Single nucleotide polymorphisms in candidate genes related to body composition and fatty acid and FAE metabolism | Assessment of the potential influence of each SNP in an individual's response to consumption of treatment oils will be conducted using 7500 Fast Real-Time PCR System | 6 weeks | 
| Gene expression of candidate genes related to body composition and fatty acid and FAE metabolism | Assessment of levels of gene expression after consumption of treatment oils will be measured using real-time quantitative PCR | 6 weeks | 
| Activity Monitoring | Assessment of 24 hour physical activity including steps taken, raw acceleration, activity counts, energy expenditures, physical activity intensity, body position, and sleep/wake measurements after consumption of treatment oils will be measured using ActiGraph GT3X+ activity monitor | 6 weeks | 
| Lipocalin-2 | Fecal and serum lipocalin-2 will be analyzed for subgroup of participants using ELISA kit | 6 weeks | 
| Lipopolysaccharide (LPS) | Serum LPS will be analyzed for subgroup of participants using the LAL assay | 6 weeks |