Vascular Effects of Triglyceride-rich Lipoproteins
12. september 2019 oppdatert 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.
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Forventet)
16
Fase
- Ikke aktuelt
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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London, Storbritannia, SE1 9NH
- Diabetes & Nutritional Sciences Division, King's College London
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
35 år til 70 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Mann
Beskrivelse
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Grunnvitenskap
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Aktiv komparator: Oleic acid
75 g high oleic acid sunflower oil.
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70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andre navn:
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Aktiv komparator: Linoleic acid
75 g high linoleic acid sunflower oil.
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70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andre navn:
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Eksperimentell: 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.
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70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andre navn:
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Eksperimentell: Docosahexaenoic acid
5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.
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70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
Tidsramme: 6 h post-meal
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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.
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6 h post-meal
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol
Tidsramme: 0, 1, 2, 3, 4, 5 and 6 h post-meal
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0, 1, 2, 3, 4, 5 and 6 h post-meal
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Incremental area under the plasma concentration versus time curve (iAUC) of glucose
Tidsramme: 0, 1, 2, 3, 4, 5 and 6 h post-meal
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0, 1, 2, 3, 4, 5 and 6 h post-meal
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Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids
Tidsramme: 0, 1, 2, 3, 4, 5 and 6 h post-meal
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0, 1, 2, 3, 4, 5 and 6 h post-meal
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Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%)
Tidsramme: 0, 1, 2, 3, 4, 5 and 6 h post-meal
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0, 1, 2, 3, 4, 5 and 6 h post-meal
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Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol
Tidsramme: 0, 1, 2, 3, 4, 5 and 6 h post-meal
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0, 1, 2, 3, 4, 5 and 6 h post-meal
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Incremental area under the unit measure versus time curve for brachial augmentation index
Tidsramme: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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Incremental area under the unit measure versus time curve for systolic blood pressure
Tidsramme: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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Incremental area under the unit measure versus time curve for diastolic blood pressure
Tidsramme: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal
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Change in digital volume pulse stiffness index
Tidsramme: 0, 2, 4 and 6 h post-meal
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0, 2, 4 and 6 h post-meal
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Change in digital volume pulse reflection index
Tidsramme: 0, 2, 4 and 6 h post-meal
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0, 2, 4 and 6 h post-meal
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Change in plasma nitrite/nitrate concentrations
Tidsramme: 0, 2, 4 and 6 h
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0, 2, 4 and 6 h
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Change in plasma 8-isoprostane F2alpha concentrations
Tidsramme: 0, 2, 4 and 6 h post-meal
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0, 2, 4 and 6 h post-meal
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Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction
Tidsramme: 4 h post-meal
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4 h post-meal
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Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction
Tidsramme: 5 h post-meal
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5 h post-meal
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juni 2012
Primær fullføring (Faktiske)
1. oktober 2012
Studiet fullført (Faktiske)
1. oktober 2012
Datoer for studieregistrering
Først innsendt
8. juni 2012
Først innsendt som oppfylte QC-kriteriene
11. juni 2012
Først lagt ut (Anslag)
13. juni 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
16. september 2019
Siste oppdatering sendt inn som oppfylte QC-kriteriene
12. september 2019
Sist bekreftet
1. september 2019
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- DRINC 11-LO-0116
- BB/1005862/1 (Annet stipend/finansieringsnummer: BBSRC)
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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