Clinical trial NCT01530893: Flavonoids, Blood Pressure and Blood Vessel Function
Official title: Are the Cardiovascular Responses of Individuals at Mild to Moderate Cardiovascular Risk Influenced by Dietary Flavonoid Sub-class and Dietary Form?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease Risk Reduction
Keywords: flavonoids
vascular function
randomised controlled trial
placebo controlled
Lead sponsor: University of East Anglia
Sponsor class: OTHER
First posted: 2012-02-10
Enrollment: 64
Sex: MALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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:

1. dietary flavonoid + placebo supplement
2. placebo food + commercially available/produced flavonoid supplement
3. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in blood vessel control (pressure and endothelial function) at time points coinciding with postprandial [anticipated] peak plasma flavonoid concentration.
timeFrame: acute postprandial; up to 24 hours, dependent on flavonoid sub-classification studied
Secondary outcomes:
measure: Differences in effects of flavonoids introduced by food matrix
timeFrame: acute postprandial; up to 24 hours dependent on flavonoid sub-classification studied
Other outcomes:
Locations:
city: Norwich
country: United Kingdom
facility: Department of Nutrition, Norwich Medical School
state: Norfolk
Study officials:
affiliation: University of East Anglia
name: Aedin Cassidy, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hazim S, Curtis PJ, Schar MY, Ostertag LM, Kay CD, Minihane AM, Cassidy A. Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. Am J Clin Nutr. 2016 Mar;103(3):694-702. doi: 10.3945/ajcn.115.125690. Epub 2016 Feb 3.
citation: Schar MY, Curtis PJ, Hazim S, Ostertag LM, Kay CD, Potter JF, Cassidy A. Orange juice-derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease. Am J Clin Nutr. 2015 May;101(5):931-8. doi: 10.3945/ajcn.114.104364. Epub 2015 Mar 18.