Vascular Effects of Triglyceride-rich Lipoproteins
12 september 2019 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Förväntat)
16
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
London, Storbritannien, SE1 9NH
- Diabetes & Nutritional Sciences Division, King's College London
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
35 år till 70 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Manlig
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Grundläggande vetenskap
- Tilldelning: Randomiserad
- Interventionsmodell: Crossover tilldelning
- Maskning: Trippel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Aktiv komparator: Oleic acid
75 g high oleic acid sunflower oil.
|
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andra namn:
|
|
Aktiv komparator: Linoleic acid
75 g high linoleic acid sunflower oil.
|
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andra namn:
|
|
Experimentell: 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.
|
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andra namn:
|
|
Experimentell: Docosahexaenoic acid
5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.
|
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol
Tidsram: 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
Tidsram: 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
Tidsram: 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 (%)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 0, 2, 4 and 6 h post-meal
|
0, 2, 4 and 6 h post-meal
|
|
Change in digital volume pulse reflection index
Tidsram: 0, 2, 4 and 6 h post-meal
|
0, 2, 4 and 6 h post-meal
|
|
Change in plasma nitrite/nitrate concentrations
Tidsram: 0, 2, 4 and 6 h
|
0, 2, 4 and 6 h
|
|
Change in plasma 8-isoprostane F2alpha concentrations
Tidsram: 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
Tidsram: 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
Tidsram: 5 h post-meal
|
5 h post-meal
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Samarbetspartners
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 juni 2012
Primärt slutförande (Faktisk)
1 oktober 2012
Avslutad studie (Faktisk)
1 oktober 2012
Studieregistreringsdatum
Först inskickad
8 juni 2012
Först inskickad som uppfyllde QC-kriterierna
11 juni 2012
Första postat (Uppskatta)
13 juni 2012
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
16 september 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
12 september 2019
Senast verifierad
1 september 2019
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- DRINC 11-LO-0116
- BB/1005862/1 (Annat bidrag/finansieringsnummer: BBSRC)
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
produkt tillverkad i och exporterad från U.S.A.
Nej
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .