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Vascular Effects of Triglyceride-rich Lipoproteins

Primary Purpose

Postprandial Period, Lipemia, Vasodilation

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
High-fat meals varying in their fatty acid composition
Sponsored by
King's College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Postprandial Period focused on measuring n-3 PUFA, Endothelial cells, Nitric oxide, Oxidative stress, Blood pressure, Vasodilation, Lipemia, Unsaturated dietary fats

Eligibility Criteria

35 Years - 70 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • Diabetes & Nutritional Sciences Division, King's College London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Experimental

Experimental

Arm Label

Oleic acid

Linoleic acid

Eicosapentaenoic acid and docosahexaenoic acid

Docosahexaenoic acid

Arm Description

75 g high oleic acid sunflower oil.

75 g high linoleic acid sunflower oil.

5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.

5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol
Incremental area under the plasma concentration versus time curve (iAUC) of glucose
Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids
Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%)
Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol
Incremental area under the unit measure versus time curve for brachial augmentation index
Incremental area under the unit measure versus time curve for systolic blood pressure
Incremental area under the unit measure versus time curve for diastolic blood pressure
Change in digital volume pulse stiffness index
Change in digital volume pulse reflection index
Change in plasma nitrite/nitrate concentrations
Change in plasma 8-isoprostane F2alpha concentrations
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction

Full Information

First Posted
June 8, 2012
Last Updated
September 12, 2019
Sponsor
King's College London
Collaborators
Royal Veterinary College
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1. Study Identification

Unique Protocol Identification Number
NCT01618071
Brief Title
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

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
King's College London
Collaborators
Royal Veterinary College

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oleic acid
Arm Type
Active Comparator
Arm Description
75 g high oleic acid sunflower oil.
Arm Title
Linoleic acid
Arm Type
Active Comparator
Arm Description
75 g high linoleic acid sunflower oil.
Arm Title
Eicosapentaenoic acid and docosahexaenoic acid
Arm Type
Experimental
Arm Description
5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.
Arm Title
Docosahexaenoic acid
Arm Type
Experimental
Arm Description
5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.
Intervention Type
Dietary Supplement
Intervention Name(s)
High-fat meals varying in their fatty acid composition
Other Intervention Name(s)
DHASCO, Purified fish oil
Intervention Description
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Primary Outcome Measure Information:
Title
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
Description
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.
Time Frame
6 h post-meal
Secondary Outcome Measure Information:
Title
Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol
Time Frame
0, 1, 2, 3, 4, 5 and 6 h post-meal
Title
Incremental area under the plasma concentration versus time curve (iAUC) of glucose
Time Frame
0, 1, 2, 3, 4, 5 and 6 h post-meal
Title
Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids
Time Frame
0, 1, 2, 3, 4, 5 and 6 h post-meal
Title
Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%)
Time Frame
0, 1, 2, 3, 4, 5 and 6 h post-meal
Title
Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol
Time Frame
0, 1, 2, 3, 4, 5 and 6 h post-meal
Title
Incremental area under the unit measure versus time curve for brachial augmentation index
Time Frame
0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
Title
Incremental area under the unit measure versus time curve for systolic blood pressure
Time Frame
0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
Title
Incremental area under the unit measure versus time curve for diastolic blood pressure
Time Frame
0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
Title
Change in digital volume pulse stiffness index
Time Frame
0, 2, 4 and 6 h post-meal
Title
Change in digital volume pulse reflection index
Time Frame
0, 2, 4 and 6 h post-meal
Title
Change in plasma nitrite/nitrate concentrations
Time Frame
0, 2, 4 and 6 h
Title
Change in plasma 8-isoprostane F2alpha concentrations
Time Frame
0, 2, 4 and 6 h post-meal
Title
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction
Time Frame
4 h post-meal
Title
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction
Time Frame
5 h post-meal

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wendy L Hall, PhD
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Diabetes & Nutritional Sciences Division, King's College London
City
London
ZIP/Postal Code
SE1 9NH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
8881715
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.
Results Reference
background
PubMed Identifier
16305504
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.
Results Reference
background
PubMed Identifier
12352009
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.
Results Reference
background
PubMed Identifier
10974050
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.
Results Reference
background
PubMed Identifier
18203893
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.
Results Reference
background
PubMed Identifier
19138437
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.
Results Reference
background
PubMed Identifier
7889892
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.
Results Reference
background
PubMed Identifier
18052925
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.
Results Reference
background
PubMed Identifier
22348439
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.
Results Reference
background
PubMed Identifier
25099540
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.
Results Reference
derived
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/25099540
Description
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