Vascular Effects of Triglyceride-rich Lipoproteins

Vasodilation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01618071
• Other study ID #: DRINC 11-LO-0116
• Secondary ID: BB/1005862/1
• Status: Completed
• Phase: N/A
• Start date: June 2012
• Est. completion date: October 2012

Study information

• Verified date: September 2019
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 35 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperlipidemias
• Lipemia
• Nitric Oxide
• Postprandial Period
• Vascular Resistance
• Vasodilation

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Diabetes & Nutritional Sciences Division, King's College London	London

Sponsors (2)

Lead Sponsor	Collaborator
King's College London	Royal Veterinary College

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction	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.	6 h post-meal
Secondary	Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol		0, 1, 2, 3, 4, 5 and 6 h post-meal
Secondary	Incremental area under the plasma concentration versus time curve (iAUC) of glucose		0, 1, 2, 3, 4, 5 and 6 h post-meal
Secondary	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
Secondary	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
Secondary	Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol		0, 1, 2, 3, 4, 5 and 6 h post-meal
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in digital volume pulse stiffness index		0, 2, 4 and 6 h post-meal
Secondary	Change in digital volume pulse reflection index		0, 2, 4 and 6 h post-meal
Secondary	Change in plasma nitrite/nitrate concentrations		0, 2, 4 and 6 h
Secondary	Change in plasma 8-isoprostane F2alpha concentrations		0, 2, 4 and 6 h post-meal
Secondary	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
Secondary	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

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