Vascular Effects of Triglyceride-rich Lipoproteins

Sponsor

King's College London (Other)

Overall Status

Completed

CT.gov ID

NCT01618071

Collaborator

Royal Veterinary College (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Many types of cardiovascular disease begin when the layer of cells lining blood vessels (endothelial cells) start to function abnormally. This causes white blood cells (monocytes) to enter the blood vessel wall and eventually form lesions. Fats from foods we consume are carried in the blood for 3-8 hours after a fatty meal in small particles known as chylomicrons (CM) and chylomicron remnants (CMR). The overall aim of this project is to investigate the idea that n-3 polyunsaturated fatty acids (PUFA) protect against heart disease by modifying the effect of CMR on endothelial cells and monocytes. We hypothesize that n3-PUFA carried in CMR reduce detrimental events which promote blood vessel damage and activate protective mechanisms to improve the function of arteries.

Condition or Disease	Intervention/Treatment	Phase
Postprandial Period Lipemia Vasodilation Vascular Resistance Nitric Oxide	Dietary Supplement: High-fat meals varying in their fatty acid composition	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Unravelling the Mechanisms of Vascular Protection by n3-PUFAs to Optimise and Support Their Use as Bioactives by the Food Industry

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oleic acid 75 g high oleic acid sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil
Active Comparator: Linoleic acid 75 g high linoleic acid sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil
Experimental: Eicosapentaenoic acid and docosahexaenoic acid 5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil
Experimental: Docosahexaenoic acid 5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil

Outcome Measures

Primary Outcome Measures

Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction [6 h post-meal]
The primary outcome of the study is activation of inflammatory/oxidative stress pathways within cultured endothelial cells following incubation with pooled postprandial lipoprotein fractions rich in chylomicron remnants. Due to the nature of this type of research this necessitates more than one primary outcome measure: the primary measures are NF-kappa-beta activation, cytokine production (e.g. interleukin-6) and reactive oxygen species generation in the cultured human endothelial cells.

Secondary Outcome Measures

Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol [0, 1, 2, 3, 4, 5 and 6 h post-meal]
Incremental area under the plasma concentration versus time curve (iAUC) of glucose [0, 1, 2, 3, 4, 5 and 6 h post-meal]
Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids [0, 1, 2, 3, 4, 5 and 6 h post-meal]
Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%) [0, 1, 2, 3, 4, 5 and 6 h post-meal]
Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol [0, 1, 2, 3, 4, 5 and 6 h post-meal]
Incremental area under the unit measure versus time curve for brachial augmentation index [0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal]
Incremental area under the unit measure versus time curve for systolic blood pressure [0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal]
Incremental area under the unit measure versus time curve for diastolic blood pressure [0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal]
Change in digital volume pulse stiffness index [0, 2, 4 and 6 h post-meal]
Change in digital volume pulse reflection index [0, 2, 4 and 6 h post-meal]
Change in plasma nitrite/nitrate concentrations [0, 2, 4 and 6 h]
Change in plasma 8-isoprostane F2alpha concentrations [0, 2, 4 and 6 h post-meal]
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction [4 h post-meal]
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction [5 h post-meal]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 70 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy males
Non-smokers
Aged 35-70 years
Fasting TAG concentrations ≥1.2 mmol/L.

Exclusion Criteria:

Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke), impaired fasting glucose/uncontrolled type 2 diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or bowel disease.
Presence of gastrointestinal disorder or use of drug, which is likely to alter gastrointestinal motility or nutrient absorption.
History of substance abuse or alcoholism (previous weekly alcohol intake >60 units/men)
Current self-reported weekly alcohol intake exceeding 28 units
Allergy or intolerance to any component of test meals
Unwilling to restrict consumption of any source of fish oil for the length of the study
Weight change of >3kg in preceding 2 months
Body Mass Index <20 and >35 kg/m2
Fasting blood cholesterol > 7.8 mmol/L
Current cigarette smoker.
Current use of lipid lowering medication