Vascular Effects of Triglyceride-rich Lipoproteins
2019年9月12日 更新者：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.
研究概览
研究类型
介入性
注册 (预期的)
16
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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London、英国、SE1 9NH
- Diabetes & Nutritional Sciences Division, King's College London
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
35年 至 70年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
男性
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器：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
其他名称：
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有源比较器：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
其他名称：
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实验性的：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
其他名称：
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实验性的：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
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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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
大体时间：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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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol
大体时间：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
大体时间：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
大体时间：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 (%)
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：5 h post-meal
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5 h post-meal
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- 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.
有用的网址
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2012年6月1日
初级完成 (实际的)
2012年10月1日
研究完成 (实际的)
2012年10月1日
研究注册日期
首次提交
2012年6月8日
首先提交符合 QC 标准的
2012年6月11日
首次发布 (估计)
2012年6月13日
研究记录更新
最后更新发布 (实际的)
2019年9月16日
上次提交的符合 QC 标准的更新
2019年9月12日
最后验证
2019年9月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.