Canola Oil Multicentre Intervention Trial (COMIT) (COMIT)

• ClinicalTrials.gov Identifier: NCT01233778
• Recruitment Status: Completed
• First Posted: November 3, 2010
• Last Update Posted: March 15, 2013
• Sponsor: Penn State University
• Collaborator: University of Manitoba
• Information provided by (Responsible Party): Penny Kris-Etherton, Penn State University

Tracking Information

• First Submitted Date: November 1, 2010
• First Posted Date: November 3, 2010
• Last Update Posted Date: March 15, 2013
• Study Start Date: October 2010
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2010)

• Endothelial Health [ Time Frame: End of diet period 1 (week 4) ]
  Study subjects will undergo endothelial health assessment by EndoPAT analysis. The EndoPat procedure will occur while the subject is lying down in a relaxed state. Throughout the study, the inflation pressure of the EndoPAT device will be electronically set to 10mm Hg below diastolic BP. Testing begins with 10 min of rest. Following rest, baseline pulse amplitude is measured from each fingertip for 5 min. Next, arterial flow is interrupted for 5 min by a cuff placed on the forearm at an occlusion pressure of 250 mmHg. Following occlusion release, pulse amplitude recording continues for 5 min.
• Endothelial Health [ Time Frame: End of diet period 2 (week 12) ]
  Study subjects will undergo endothelial health assessment by EndoPAT analysis. The EndoPat procedure will occur while the subject is lying down in a relaxed state. Throughout the study, the inflation pressure of the EndoPAT device will be electronically set to 10mm Hg below diastolic BP. Testing begins with 10 min of rest. Following rest, baseline pulse amplitude is measured from each fingertip for 5 min. Next, arterial flow is interrupted for 5 min by a cuff placed on the forearm at an occlusion pressure of 250 mmHg. Following occlusion release, pulse amplitude recording continues for 5 min.
• Endothelial Health [ Time Frame: End of diet period 3 (week 20) ]
  Study subjects will undergo endothelial health assessment by EndoPAT analysis. The EndoPat procedure will occur while the subject is lying down in a relaxed state. Throughout the study, the inflation pressure of the EndoPAT device will be electronically set to 10mm Hg below diastolic BP. Testing begins with 10 min of rest. Following rest, baseline pulse amplitude is measured from each fingertip for 5 min. Next, arterial flow is interrupted for 5 min by a cuff placed on the forearm at an occlusion pressure of 250 mmHg. Following occlusion release, pulse amplitude recording continues for 5 min.
• Endothelial Health [ Time Frame: End of diet period 4 (week 28) ]
  Study subjects will undergo endothelial health assessment by EndoPAT analysis. The EndoPat procedure will occur while the subject is lying down in a relaxed state. Throughout the study, the inflation pressure of the EndoPAT device will be electronically set to 10mm Hg below diastolic BP. Testing begins with 10 min of rest. Following rest, baseline pulse amplitude is measured from each fingertip for 5 min. Next, arterial flow is interrupted for 5 min by a cuff placed on the forearm at an occlusion pressure of 250 mmHg. Following occlusion release, pulse amplitude recording continues for 5 min.
• Endothelial Health [ Time Frame: End of diet period 5 (week 36) ]
  Study subjects will undergo endothelial health assessment by EndoPAT analysis. The EndoPat procedure will occur while the subject is lying down in a relaxed state. Throughout the study, the inflation pressure of the EndoPAT device will be electronically set to 10mm Hg below diastolic BP. Testing begins with 10 min of rest. Following rest, baseline pulse amplitude is measured from each fingertip for 5 min. Next, arterial flow is interrupted for 5 min by a cuff placed on the forearm at an occlusion pressure of 250 mmHg. Following occlusion release, pulse amplitude recording continues for 5 min.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 19, 2011)

• Body Composition [ Time Frame: Week 4, 12, 20, 28 and 36 - End of each diet period ]
  To assess regional changes in body fat deposition, subjects will undergo a dual energy X-ray absorptiometry (DXA) scan at baseline (beginning of study) and end of each intervention period. Waist circumference measurements also will be taken at this time to track how much fat is lost from the abdominal area of the body.
• Production of long chain fatty acids [ Time Frame: Week 4, 12, 20, 28 and 36 - End of each diet period ]
  On the 29th day of each diet phase you will be asked to consume three tablespoons of tagged water (known as deuterium). The movement of these tagged materials will allow us to assess the quantity of long chain fatty acids (EPA and DHA) that your body is producing in response to your diet. All of the above tagged materials are non-radioactive, non-toxic, and do not pose any health risk to you. Another fasting blood sample will be obtained when you return the next morning.
• Plasma Lipids [ Time Frame: Week 4, 12, 20, 28 and 36 - End of each diet period ]
  Twelve-hour fasting blood samples (30ml) will be collected on day 1, 2, 29 and 30 for analyses of plasma lipids. Blood samples obtained on day 1 and 2 will be used to measure baseline values for study endpoints, whereas blood samples obtained on the two last days will be used to measure final endpoint values.
• Plasma Cytokines [ Time Frame: Week 4, 12, 20, 28 and 36 - End of each diet period ]
  Twelve-hour fasting blood samples (30ml) will be collected on day 1, 2, 29 and 30 for analyses of C-reactive protein and inflammatory cytokines. Blood samples obtained on day 1 and 2 will be used to measure baseline values for study endpoints, whereas blood samples obtained on the two last days will be used to measure final endpoint values.

Original Secondary Outcome Measures (submitted: November 2, 2010)

• Body Composition [ Time Frame: End of diet period ]
  To assess regional changes in body fat deposition, subjects will undergo a dual energy X-ray absorptiometry (DXA) scan at baseline (beginning of study) and end of each intervention period. Waist circumference measurements also will be taken at this time to track how much fat is lost from the abdominal area of the body.
• Production of long chain fatty acids [ Time Frame: End of diet period ]
  On the 29th day of each diet phase you will be asked to consume three tablespoons of tagged water (known as deuterium). The movement of these tagged materials will allow us to assess the quantity of long chain fatty acids (EPA and DHA) that your body is producing in response to your diet. All of the above tagged materials are non-radioactive, non-toxic, and do not pose any health risk to you. Another fasting blood sample will be obtained when you return the next morning.
• Plasma Lipids [ Time Frame: On two consecutive days at the end of diet period ]
  Twelve-hour fasting blood samples (30ml) will be collected on day 1, 2, 29 and 30 for analyses of plasma lipids. Blood samples obtained on day 1 and 2 will be used to measure baseline values for study endpoints, whereas blood samples obtained on the two last days will be used to measure final endpoint values.
• Plasma Cytokines [ Time Frame: End of diet period ]
  Twelve-hour fasting blood samples (30ml) will be collected on day 1, 2, 29 and 30 for analyses of C-reactive protein and inflammatory cytokines. Blood samples obtained on day 1 and 2 will be used to measure baseline values for study endpoints, whereas blood samples obtained on the two last days will be used to measure final endpoint values.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Canola Oil Multicentre Intervention Trial (COMIT)
• Official Title: Canola and Flax Oils in Modulation of Vascular Function and Biomarkers of Cardiovascular Disease Risk
• Brief Summary: The objectives of this study are to examine how the consumption of treatment oils (including canola oil, DHA enriched canola-oil, high oleic acid canola oil, flax oil, and safflower oil) influence endothelial function, inflammation, oxidation, body composition, and plasma lipoprotein characterization.

Detailed Description

The consequence of total fat consumption on circulating plasma lipids and the incidence of cardiovascular disease has long been a central theme in nutrition research. Less well known is the influence of specific fatty acids on vascular endothelial function and the oxidative and inflammatory responses characteristic of atherogenesis. Omega 3 ( ω-3) fatty acids, including plant derived alpha-linolenic acid (18:3n-3, ALA) and marine derived eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) have been shown to effectively modulate multiple cardiovascular risk factors in epidemiological, animal model and human clinical investigations. ALA is most commonly consumed as a major component of dietary canola and flaxseed oils and has a recommended intake of 1.1 and 1.6 g/d for women and men, respectively. EPA and DHA are consumed as fatty fish or fish oil and algae supplements with current recommended intakes of 500 mg/d (combined EPA and DHA).

ALA is thought to improve cardiovascular health by modulating circulating lipid concentrations, altering membrane structure and function by enhancing the total ω-3 fatty acid content of cell membrane phospholipids, and reducing inflammatory reactions by blocking the formation of arachidonic acid derived eicosanoids. However, there are extensive knowledge gaps in our understanding of the molecular mechanisms and clinical efficacy of ω-3 fatty acids in human health and disease prevention. Therefore, the purpose of this study is to further examine these relationships.

Feeding protocol and study treatments:

The study will proceed as a double blind, randomized cross-over controlled feeding study. Each treatment phase will be 30 days in duration, separated by 4-week washout periods. Subjects will consume a fixed composition of a precisely controlled basal, weight-maintaining diet (35% energy from fat, 50% carbohydrate, and 15% protein) supplemented with 60g/d of the following treatment oils: 1) canola oil; 2) DHA enriched canola-oil; 3) high oleic acid canola oil; 4) flax/corn oil (40:60); or 5) safflower/corn oil (75:25). Study diets will be prepared in a metabolic kitchen facility at each clinical site. Three isocaloric meals will be prepared each day for every subject. A 7-day rotating menu cycle will be used. Subjects will consume at least 1 of 3 daily meals under supervision. The other meals will be prepared and packed for every subject to be taken out. The study control and intervention oils will be delivered in milkshakes provided twice daily. Subjects will be instructed to consume only the prepared meals and limit their intake of alcohol to 2 drinks/week and caffeinated calorie free beverages to 40oz (5 drinks) per day. Diets will be planned for every subject according to his/her energy requirements and will be nutritionally adequate.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Prevention
• Condition: Cardiovascular Disease

Intervention

• Dietary Supplement: Canola Oil
  60g Canola oil daily per 3000kcal diet provided in a supplemental shake
• Dietary Supplement: High Oleic Acid + DHA Canola Oil
  60g high oleic acid canola oil + DHA daily per 3000kcal provided in a supplemental shake
• Dietary Supplement: High Oleic Acid Canola Oil
  60g high oleic acid canola oil daily per 3000kcal provided in a supplemental shake
• Dietary Supplement: Flax Oil
  36g flax oil + 24g safflower oil daily per 3000kcal provided in a supplemental shake
• Dietary Supplement: Safflower Oil
  45g safflower oil + 15g corn oil daily per 3000kcal provided in a supplemental shake

Study Arms

• Experimental: Canola Oil
  Intervention: Dietary Supplement: Canola Oil
• Experimental: High Oleic Acid Canola + DHA
  Intervention: Dietary Supplement: High Oleic Acid + DHA Canola Oil
• Experimental: High Oleic Canola Oil
  Intervention: Dietary Supplement: High Oleic Acid Canola Oil
• Experimental: Flax & Safflower Oil (60:40)
  Intervention: Dietary Supplement: Flax Oil
• Experimental: Safflower & Corn Oil (75:25)
  Intervention: Dietary Supplement: Safflower Oil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 14, 2013): 43
• Original Estimated Enrollment (submitted: November 2, 2010): 48
• Actual Study Completion Date: April 2012
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 20-65 years
• BMI = 22-32 kg/m2

In addition, eligibility will be based on metabolic syndrome criteria where we define eligibility on the basis of subjects having elevated waist circumference + 1 or more of the remaining 5 criteria:

• Elevated waist circumference - > 102 cm for men and >88 cm for women
• Elevated triglycerides - ≥ 1.7 mmol/L ( ≥150mg/dl) ( no upper limit)
• Reduced HDL - < 1 mmol/L (<40 mg/dl) for men and < 1.3 mmol/L (<50 mg/dl)for women
• Fasting glucose - ≥ 100 mg/dl (no upper limit)

• Elevated blood pressure - systolic ≥130 and/or diastolic ≥85 mm HG

  • Unmedicated participants - upper limit of Stage 1 Hypertension: systolic ≤ 159 and/or diastolic ≤ 99 mm HG and participants must be free of end stage/target organ disease symptoms
  • BP medicated participants: acceptable as long as individuals meet the specified blood pressure range of <140/90 mmHg, and have been stable for at least 6 months.

Exclusion Criteria:

• Smokers**
• History of thyroid disease, diabetes, kidney or liver disease, heart disease, or other chronic diseases
• Heavy alcohol consumption (>14 drinks/week)
• Chronic anti-inflammatory medication use
• Lactation, pregnancy, or desire to become pregnant during the study
• Taking lipid lowering medications (cholestyramine, colestipol, niacin, clofibrate, gemfibrozil probucol, HMG CoA reductase inhibitors) within the last three months
• Not willing to refrain from blood/plasma donation during the study period

• Gall bladder removal

  • For purposes of the this study non-smoking is defined as >6 months smoke-free; there is some evidence to show that smoking cessation increases HDL levels and 6 months is adequate time for this to stabilize, however this time span was chosen based on the decreased rate of relapse after 6 months.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01233778
• Other Study ID Numbers: PKE COMIT
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Penny Kris-Etherton, Penn State University
• Original Responsible Party: Penny Kris-Etherton, PhD, Penn State University
• Current Study Sponsor: Penn State University
• Original Study Sponsor: Same as current
• Collaborators: University of Manitoba

Investigators

• Principal Investigator: Penny M Kris-Etherton, PhD, RD; Penn State University

• PRS Account: Penn State University
• Verification Date: March 2013