Clinical trial NCT01618071: Vascular Effects of Triglyceride-rich Lipoproteins
Official title: Unravelling the Mechanisms of Vascular Protection by n3-PUFAs to Optimise and Support Their Use as Bioactives by the Food Industry
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postprandial Period
Lipemia
Vasodilation
Vascular Resistance
Nitric Oxide
Keywords: n-3 PUFA
Endothelial cells
Nitric oxide
Oxidative stress
Blood pressure
Vasodilation
Lipemia
Unsaturated dietary fats
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Royal Veterinary College
First posted: 2012-06-13
Enrollment: 16
Sex: MALE
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
timeFrame: 6 h post-meal
Secondary outcomes:
measure: Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol
timeFrame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
measure: Incremental area under the plasma concentration versus time curve (iAUC) of glucose
timeFrame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
measure: Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids
timeFrame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
measure: Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%)
timeFrame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
measure: Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol
timeFrame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
measure: Incremental area under the unit measure versus time curve for brachial augmentation index
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
measure: Incremental area under the unit measure versus time curve for systolic blood pressure
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
measure: Incremental area under the unit measure versus time curve for diastolic blood pressure
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
measure: Change in digital volume pulse stiffness index
timeFrame: 0, 2, 4 and 6 h post-meal
measure: Change in digital volume pulse reflection index
timeFrame: 0, 2, 4 and 6 h post-meal
measure: Change in plasma nitrite/nitrate concentrations
timeFrame: 0, 2, 4 and 6 h
measure: Change in plasma 8-isoprostane F2alpha concentrations
timeFrame: 0, 2, 4 and 6 h post-meal
measure: Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction
timeFrame: 4 h post-meal
measure: Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction
timeFrame: 5 h post-meal
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Diabetes & Nutritional Sciences Division, King's College London
Study officials:
affiliation: King's College London
name: Wendy L Hall, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lambert MS, Botham KM, Mayes PA. Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants. Br J Nutr. 1996 Sep;76(3):435-45. doi: 10.1079/bjn19960048.
citation: Botham KM, Bravo E, Elliott J, Wheeler-Jones CP. Direct interaction of dietary lipids carried in chylomicron remnants with cells of the artery wall: implications for atherosclerosis development. Curr Pharm Des. 2005;11(28):3681-95. doi: 10.2174/138161205774580732.
citation: Proctor SD, Vine DF, Mamo JC. Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis. Curr Opin Lipidol. 2002 Oct;13(5):461-70. doi: 10.1097/00041433-200210000-00001.
citation: Marcoux C, Hopkins PN, Wang T, Leary ET, Nakajima K, Davignon J, Cohn JS. Remnant-like particle cholesterol and triglyceride levels of hypertriglyceridemic patients in the fed and fasted state. J Lipid Res. 2000 Sep;41(9):1428-36.
citation: Hall WL, Sanders KA, Sanders TA, Chowienczyk PJ. A high-fat meal enriched with eicosapentaenoic acid reduces postprandial arterial stiffness measured by digital volume pulse analysis in healthy men. J Nutr. 2008 Feb;138(2):287-91. doi: 10.1093/jn/138.2.287.
citation: Burdge GC, Powell J, Dadd T, Talbot D, Civil J, Calder PC. Acute consumption of fish oil improves postprandial VLDL profiles in healthy men aged 50-65 years. Br J Nutr. 2009 Jul;102(1):160-5. doi: 10.1017/S0007114508143550. Epub 2009 Jan 13.
citation: Zampelas A, Peel AS, Gould BJ, Wright J, Williams CM. Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men. Eur J Clin Nutr. 1994 Dec;48(12):842-8.
citation: Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin Sci (Lond). 2008 Jun;114(11):679-86. doi: 10.1042/CS20070277.
citation: Rontoyanni VG, Hall WL, Pombo-Rodrigues S, Appleton A, Chung R, Sanders TA. A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. Br J Nutr. 2012 Aug;108(3):492-9. doi: 10.1017/S0007114511005721. Epub 2012 Feb 21.
citation: Purcell R, Latham SH, Botham KM, Hall WL, Wheeler-Jones CP. High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2alpha concentrations relative to a control high-oleic acid meal: a randomized controlled trial. Am J Clin Nutr. 2014 Oct;100(4):1019-28. doi: 10.3945/ajcn.114.091223. Epub 2014 Aug 6.