Elucidation and Monitoring Postprandial Endothelial Function

Study Overview
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Brief Summary
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The primary aim of this study is to evaluate the effect of a high fat challenge on several measures of endothelial function. The secondary aim of this study is to elucidate the mechanism of postprandial endothelial dysfunction and to identify early biomarkers

Detailed Description
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Endothelial dysfunction (ED) is a hallmark for the initial stage of vascular dysfunction and has been associated with diet-related disorders such as cardiovascular disease. This makes prevention of ED an important health target. From previous studies we know that a high-fat (HF) meal (challenge) impairs postprandial endothelial function (EF). Current studies only evaluated the effect of a HF meal on Flow Mediated Dilatation (FMD), a measure of macro vascular EF. This methodology (FMD) however, is time consuming and large variations in reproducibility are reported in literature. The question remains whether other types of macro- and micro vascular EF measurements can be used to observe ED after a HF meal that are more accurate, faster and easier to perform. In addition, it is know that the postprandial phase results in activation of leukocytes. This activation of leukocytes is likely to contribute to ED, but the exact underling mechanism remains unclear.

Official Title
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Elucidation and Monitoring Postprandial Endothelial Function

Conditions
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Cardiovascular Disease, Endothelial Dysfunction

Intervention / Treatment
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* Dietary Supplement: high fat meal
* Dietary Supplement: control meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male, caucasian Exclusion Criteria: • Allergic to cow milk or dairy products Body mass index (BMI) < 18 or > 25 kg/m2 Urine glucose concentrations outside normal ranges (>0,25 g/l) Fasting blood glucose outside the normal range (3 - 5.5 mmol/L) Tobacco smoking Taking medication or food supplements. Received inoculations within 2 months of starting the study or planned to during the study Donated or intended to donate blood from 2 months before the study till two months after the study Blood Hb values below 8.4 mmol/L Diagnosed with any long-term medical condition (e.g., diabetes, hemophilia, cardiovascular disease, anemia, gastrointestinal disease, renal failure) High blood pressure (systolic BP> 140 mmHg and/or diastolic BP>90 mmHg)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High fat meal<br>A high fat milkshake containing 95g of fat | Dietary Supplement: high fat meal<br>* milkshake containing 95g fat<br>|
| Experimental: Control meal<br>Milkshake comparable with a normal breakfast | Dietary Supplement: control meal<br>* milkshake comparable with a normal breakfast<br>|
| Experimental: High fat meal 2<br>A high fat milkshake containing 95g of fat | Dietary Supplement: high fat meal<br>* milkshake containing 95g fat<br>|
| Experimental: High fat meal 3<br>A high fat milkshake containing 95g of fat | Dietary Supplement: high fat meal<br>* milkshake containing 95g fat<br>|
| Experimental: Control meal 2<br>Milkshake comparable with a normal breakfast | Dietary Supplement: control meal<br>* milkshake comparable with a normal breakfast<br>|
| Experimental: Control meal 3<br>Milkshake comparable with a normal breakfast | Dietary Supplement: control meal<br>* milkshake comparable with a normal breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macrovascular local arterial stiffness by echo-tracking |  | 0, 3, 6 hours | 
| Macrovascular regional arterial stiffness by tonometry |  | 0, 3, 6 h | 
| Macrovascular circulation by flow mediated dilatation |  | 0, 3, 6h | 
| Microvascular circulation by iontophoresis/laser doppler |  | 0, 3, 6h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PBMC gene expression profiles |  | 0, 1, 2, 3, 5, 6 hours | 
| Leukocyte activation markers |  | 0, 3, 6h | 
| cytokine profiles |  | 0, 1, 2, 3, 5, 6 hours | 
| known plasma markers of ED |  | 0, 1, 2, 3, 5, 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelium,, postprandial, microvascular, macrovascular