Flavonoids, Blood Pressure and Blood Vessel Function

Study Overview
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Brief Summary
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The primary aim of this placebo-controlled study is to determine whether flavonoids beneficially affect markers of cardiovascular disease risk in healthy subjects at elevated cardiovascular risk. The underlying mechanisms of action of flavonoids will be assessed on blood biomarkers and we will assess the effects of the food matrix, and aspects of isoflavone metabolism.

Detailed Description
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The study population will be healthy males (aged 50-75 years) at elevated risk of cardiovascular (CV) disease. A target of 60 participants will be required to complete the study and a total of 70 subjects will be targeted (n=70 subjects *  85% anticipated completion rate = 60 subjects to complete the study). This placebo-controlled study will test the relative efficacy of 4 different flavonoid sub-classes ((i) flavan-3-ol, (ii) anthocyanin, (iii) flavanone and (iv) isoflavone). Accordingly, subjects will be randomised to one of the four flavonoid study groups ((i) to (iv) outlined above), and then will consume each of the following treatments in random order: dietary flavonoid + placebo supplement placebo food + commercially available/produced flavonoid supplement placebo food + placebo supplement Additionally, an isoflavone metabolite will be fed to establish potential vascular effects. Each sub-class will be assessed separately and a 1 week wash-out period between treatments will be observed. At each assessment visit, vascular function will be assessed pre- and post-intervention, with subsequent assessments made to coincide with anticipated peak plasma concentrations. Dietary intake will be monitored during the study and participants will be required to adhere to a range of dietary and lifestyle restrictions within 3 days of each assessment to reduce potential confounding of the data assessment of interest. A standard battery of vascular function tests will be performed on all intervention groups, with each assessment visit performed in an identical manner.

Official Title
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Are the Cardiovascular Responses of Individuals at Mild to Moderate Cardiovascular Risk Influenced by Dietary Flavonoid Sub-class and Dietary Form?

Conditions
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Cardiovascular Disease Risk Reduction

Intervention / Treatment
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* Dietary Supplement: Flavanone - supplement
* Other: Flavanone - food
* Other: Flavanone - placebo
* Dietary Supplement: Isoflavone - supplement
* Other: Isoflavone - food
* Other: Isoflavone - placebo
* Dietary Supplement: Isoflavone - metabolite supplement
* Dietary Supplement: Flavan-3-ol - supplement
* Other: Flavan-3-ol - food
* Other: Flavan-3-ol - placebo
* Dietary Supplement: Anthocyanin - supplement
* Other: Anthocyanin - food
* Other: Anthocyanin - placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males 50 to 75 years old At elevated risk of CV disease Screening blood pressure of < 160/90mmHg (at rest) Successful biochemical, haematological and urinalysis assessment at screening (as judged by clinical advisor) Exclusion Criteria: Current smokers, or ex-smokers ceasing < 3 months ago Subjects with existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures (as judged by clinical advisor) Those with known allergies to the intervention treatments Those unprepared to adhere to dietary restrictions during the trial Parallel participation in another research project which involves concurrent dietary intervention and/or sampling of biological fluids/material Having vaccinations (excluding the flu vaccination) or antibiotics within 3 months of start of trial, and those with vaccinations scheduled for during the trial Taking flavonoid containing food / dietary supplements likely to affect the study results Prescribed lipid lowering, hypertension, vasodilators (e.g. Viagra) or antibiotic medication Unsatisfactory biochemical, haematological or urinary assessment at screening, indicating abnormal; renal or liver function, full blood profile, impaired glucose handling, deranged lipids or measurements considered to be counter indicative of the study by the clinical advisor

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group A: flavanones<br>All experimental days will be exactly the same. All volunteers will attend the clinical research and trial unit in a fasted state. Prior to test administration, baseline vascular function will be assessed and biological samples taken by a trained and qualified research nurse. Subsequently, assessments will be repeated at times corresponding to anticipated peak plasma concentration of the flavonoid of interest. | Dietary Supplement: Flavanone - supplement<br>* acute single optimal dose<br>Other: Flavanone - food<br>* acute single dose<br>Other: Flavanone - placebo<br>* acute single dose (flavanone free)<br>|
| Experimental: Intervention group B: isoflavones<br>All experimental days will be exactly the same. All volunteers will attend the clinical research and trial unit in a fasted state. Prior to test administration, baseline vascular function will be assessed and biological samples taken by a trained and qualified research nurse. Subsequently, assessments will be repeated at times corresponding to anticipated peak plasma concentration of the flavonoid of interest. | Dietary Supplement: Isoflavone - supplement<br>* acute single optimal dose<br>Other: Isoflavone - food<br>* acute single optimal dose<br>Other: Isoflavone - placebo<br>* acute single dose (isoflavone free)<br>Dietary Supplement: Isoflavone - metabolite supplement<br>* acute single optimal dose of commercial product<br>|
| Experimental: Intervention group C: Flavan-3-ols<br>All experimental days will be exactly the same. All volunteers will attend the clinical research and trial unit in a fasted state. Prior to test administration, baseline vascular function will be assessed and biological samples taken by a trained and qualified research nurse. Subsequently, assessments will be repeated at times corresponding to anticipated peak plasma concentration of the flavonoid of interest. | Dietary Supplement: Flavan-3-ol - supplement<br>* acute single optimal dose<br>Other: Flavan-3-ol - food<br>* acute single optimal dose<br>Other: Flavan-3-ol - placebo<br>* acute single dose (flavan-3-ol free)<br>|
| Experimental: Intervention group D: Anthocyanins<br>All experimental days will be exactly the same. All volunteers will attend the clinical research and trial unit in a fasted state. Prior to test administration, baseline vascular function will be assessed and biological samples taken by a trained and qualified research nurse. Subsequently, assessments will be repeated at times corresponding to anticipated peak plasma concentration of the flavonoid of interest. | Dietary Supplement: Anthocyanin - supplement<br>* acute single optimal dose<br>Other: Anthocyanin - food<br>* acute single optimal dose<br>Other: Anthocyanin - placebo<br>* acute single dose (anthocyanin free)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in blood vessel control (pressure and endothelial function) at time points coinciding with postprandial [anticipated] peak plasma flavonoid concentration. | Assessment of vascular function | acute postprandial; up to 24 hours, dependent on flavonoid sub-classification studied | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in effects of flavonoids introduced by food matrix |  | acute postprandial; up to 24 hours dependent on flavonoid sub-classification studied | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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flavonoids, vascular function, randomised controlled trial, placebo controlled