Vascular Effects of Triglyceride-rich Lipoproteins

September 12, 2019 updated by: Dr Wendy Hall, King's College London

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SE1 9NH
        • Diabetes & Nutritional Sciences Division, King's College London

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
Time Frame: 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.
6 h post-meal

Secondary Outcome Measures

Outcome Measure
Time Frame
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
0, 1, 2, 3, 4, 5 and 6 h post-meal
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
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
Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
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 (%)
Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal
0, 1, 2, 3, 4, 5 and 6 h post-meal
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
0, 1, 2, 3, 4, 5 and 6 h post-meal
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
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
Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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
Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
Change in digital volume pulse stiffness index
Time Frame: 0, 2, 4 and 6 h post-meal
0, 2, 4 and 6 h post-meal
Change in digital volume pulse reflection index
Time Frame: 0, 2, 4 and 6 h post-meal
0, 2, 4 and 6 h post-meal
Change in plasma nitrite/nitrate concentrations
Time Frame: 0, 2, 4 and 6 h
0, 2, 4 and 6 h
Change in plasma 8-isoprostane F2alpha concentrations
Time Frame: 0, 2, 4 and 6 h post-meal
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
Time Frame: 4 h post-meal
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
Time Frame: 5 h post-meal
5 h post-meal

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King's College London

Collaborators

Royal Veterinary College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

June 8, 2012

First Submitted That Met QC Criteria

June 11, 2012

First Posted (Estimate)

June 13, 2012

Study Record Updates

Last Update Posted (Actual)

September 16, 2019

Last Update Submitted That Met QC Criteria

September 12, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DRINC 11-LO-0116
  • BB/1005862/1 (Other Grant/Funding Number: BBSRC)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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