Flavonoids, Blood Pressure and Blood Vessel Function (FASTCHECK)

• ClinicalTrials.gov Identifier: NCT01530893
• Recruitment Status: Completed
• First Posted: February 10, 2012
• Last Update Posted: February 28, 2014
• Sponsor: University of East Anglia
• Information provided by (Responsible Party): University of East Anglia

Tracking Information

• First Submitted Date: February 1, 2012
• First Posted Date: February 10, 2012
• Last Update Posted Date: February 28, 2014
• Study Start Date: February 2012
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2012)

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

Assessment of vascular function

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: February 7, 2012): Differences in effects of flavonoids introduced by food matrix [ Time Frame: acute postprandial; up to 24 hours dependent on flavonoid sub-classification studied ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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?

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Cardiovascular Disease Risk Reduction

Intervention

• Dietary Supplement: Flavanone - supplement
  acute single optimal dose
• Other: Flavanone - food
  acute single dose
• Other: Flavanone - placebo
  acute single dose (flavanone free)
• Dietary Supplement: Isoflavone - supplement
  acute single optimal dose
• Other: Isoflavone - food
  acute single optimal dose
• Other: Isoflavone - placebo
  acute single dose (isoflavone free)
• Dietary Supplement: Isoflavone - metabolite supplement
  acute single optimal dose of commercial product
• Dietary Supplement: Flavan-3-ol - supplement
  acute single optimal dose
• Other: Flavan-3-ol - food
  acute single optimal dose
• Other: Flavan-3-ol - placebo
  acute single dose (flavan-3-ol free)
• Dietary Supplement: Anthocyanin - supplement
  acute single optimal dose
• Other: Anthocyanin - food
  acute single optimal dose
• Other: Anthocyanin - placebo
  acute single dose (anthocyanin free)

Study Arms

• Experimental: Intervention group A: flavanones
  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.
  Interventions:

  • Dietary Supplement: Flavanone - supplement
  • Other: Flavanone - food
  • Other: Flavanone - placebo
• Experimental: Intervention group B: isoflavones
  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.
  Interventions:

  • Dietary Supplement: Isoflavone - supplement
  • Other: Isoflavone - food
  • Other: Isoflavone - placebo
  • Dietary Supplement: Isoflavone - metabolite supplement
• Experimental: Intervention group C: Flavan-3-ols
  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.
  Interventions:

  • Dietary Supplement: Flavan-3-ol - supplement
  • Other: Flavan-3-ol - food
  • Other: Flavan-3-ol - placebo
• Experimental: Intervention group D: Anthocyanins
  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.
  Interventions:

  • Dietary Supplement: Anthocyanin - supplement
  • Other: Anthocyanin - food
  • Other: Anthocyanin - placebo

Publications *

• Hazim S, Curtis PJ, Schär 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.
• Schär 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 27, 2014): 64
• Original Estimated Enrollment (submitted: February 7, 2012): 70
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 50 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01530893
• Other Study ID Numbers: FASTCHECK
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of East Anglia
• Study Sponsor: University of East Anglia
• Collaborators: Not Provided

Investigators

• Principal Investigator: Aedin Cassidy, PhD; University of East Anglia

• PRS Account: University of East Anglia
• Verification Date: February 2014