The Effects of Flavonoid Supplementation on Cognition and Neural Mechanisms in Healthy Older Adults (CoCo_Chronic)

May 22, 2018 updated by: Jeremy Paul Edward Spencer, University of Reading

Mechanistic Assessment of the Acute and Chronic Cognitive Effects of Flavanol/Anthocyanin Intervention in Humans - Chronic Trial

A double-blind, randomised, controlled, parallel arm chronic intervention trial with healthy older adults will be conducted to determine the effect of a flavonoid-rich supplement on cognitive function, peripheral arterial health and brain mechanisms. It is predicted that chronic flavonoid supplementation will result in cognitive benefits and that these may be due to beneficial effects of flavonoids on vascular and brain function.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There has recently been an increasing interest in the potential of flavonoids, plant derived compounds found in foods such as fruit and vegetables, to improve cognitive function. Research suggests that flavonoids improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects, for example by increasing cerebral blood flow (CBF), protecting vulnerable neurons, or by stimulating neuronal function and growth. The proposed research will involve a parallel design chronic dietary supplementation trial using a flavonoid-supplement and a matched control containing no flavonoids, to investigate long-term changes in cognitive performance. To understand the neural mechanisms behind potential changes in cognitive performance, resting cerebral blood flow (CBF), blood-oxygen level dependent (BOLD) response during two sensitive tests of cognitive performance, and structural brain changes will be measured in a group of healthy elderly adults (N=70, age range 60-75 years) using magnetic resonance imaging (MRI). Additionally, peripheral vascular health will be measured using flow mediated dilatation (FMD), and bioavailability of flavonoid monomers and metabolites will be determined through analysis of plasma and urine samples. Biomarkers in the blood associated with vascular health and neural functioning as well as markers of interest in relation to the possible mechanisms of action of flavonoids will also be measured. All endpoints will be acquired before and after a 24-week chronic supplementation of either a high flavonoid supplementation or a control product, consumed in addition to participants' normal diet. Measures will also be taken following a 12-week post-intervention washout period in order to investigate whether any beneficial effects are sustained following cessation of supplementation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Berkshire
      • Reading, Berkshire, United Kingdom, RG6 5SG
        • Hugh Sinclair Unit of Human Nutrition, University of Reading

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

  • Males and females aged 60-75 years
  • English as primary language, able to understand the study information sheet, follow instructions in English and give informed consent
  • Non-smokers
  • Alcohol consumption should be within the current National Health Service (NHS) recommendation - women: ≤21 units per week (max 3 per day), 1 large 250mL glass of wine (Alcohol By Volume 12%) is 3 units; men: ≤ 28 units per week (max 4 per day), 1 pint of strong lager/beer/cider (Alcohol By Volume 5.2%) is 3 units
  • BP <150/90 (determined at screening)
  • BMI <30 (determined at screening)

  • Full blood count parameters within the normal range, specifically:

    • Haemoglobin to check for anaemia (>12.5 g/dL for males and >11.5 g/dL for females)
    • Total white cell count (3.6-11.0 x109/L)

    • Differential count:

      • Neutrophils (1.8 - 7.5 x109/L)
      • Lymphocytes (1.0 - 4.0 x109/L)
      • Monocytes (0.2 - 0.8 x109/L)
      • Eosinophils (0.1 - 0.4 x109/L)
      • Basophils (0.02 - 0.1 x109/L)
    • Normal platelet function (platelet count 140-400 x109/L)
    • Red cell count (4.50-6.50 x1012/L for males; 3.80-5.80 x1012/L for females)
    • Haematocrit (0.40-0.54 L/L for males; 0.37-0.47 L/L for females)
    • Mean Cell Volume (80-100 fL)
    • Mean Cell Haemoglobin (27-32 pg)
    • Reticulocyte Count (0.2-2.0 %)

  • The following blood parameters within the normal range:

    • Liver function (gamma-glutamyl transpeptidase [GGT] level < 80 IU/L, alanine transaminase [ALT] < 30 U/L, alkaline phosphatase [ALP] < 320 U/L),
    • Kidney function (total bilirubin ≤ 22 μmol/L, creatinine ≤ 106 μmol/L, uric acid < 506 μmol/L),
    • Fasting blood glucose level (< 7 mmol/L),
    • Triglycerides (< 2.2 mmol/L)
    • Plasma cholesterol (< 8 mmol/L)

EXCLUSION CRITERIA:

  • General global cognitive impairment (Mini Mental State Examination score < 24)
  • Un-corrected vision or hearing problems
  • Speech or communication difficulties
  • Currently suffering from depression (Brief Symptom Inventory score of ≥ 11)
  • Diagnosed with any learning difficulty such as Dyslexia or Dyspraxia
  • Sensitive/allergic to the intervention or any of the study foods

  • Suffering from any form of clinically diagnosed disease, including:

    • Major mental illness (current or previous episode with hospitalization)
    • Chronic fatigue syndrome
    • Liver disease
    • Diabetes mellitus
    • Heart disease or myocardial infarction
  • Taking blood pressure medication, anticoagulants, anti-platelet medication or antidepressants
  • On a weight reducing dietary regimen or taking any dietary supplements (including dietary fatty acids), unless willing to temporarily refrain from taking dietary supplements for the duration of the study
  • Subjects consuming more than seven portions of fruit and vegetables a day
  • Subjects consuming more than five cups of tea a day
  • Men taking part in more than 10.5 hours of moderate to vigorous exercise per week and women taking part in more than 7 hours of moderate to vigorous exercise per week (assessed on an individual basis to avoid recruitment of people who exercise too vigorously)
  • Taking illegal substances

MRI part:

  • Has a heart pacemaker or metal implants (including any non-removable ferro-magnetic dental items)
  • Any body piercing items that cannot be removed
  • Is claustrophobic

Note: Participation in other research trials within the last month will need to be declared and may affect the start date for participation in the current trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Active
Cocoa-Flavanol Supplements: 3 capsules per day each containing 300mg (total dose of 900mg daily) for 24 weeks
Dietary supplement: Cocoa-Flavanol Supplements
3 capsules each containing 300mg cocoa flavanols (total daily dose of 900mg cocoa-flavanols).
PLACEBO_COMPARATOR: Control
Control Supplements: 0mg cocoa-flavanols per day for 24 weeks
Dietary supplement: Control Supplements
3 capsules each containing 0mg cocoa-flavanols

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Cognitive Performance (0-24 weeks)
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Composite measure of global cognitive function (scores from different cognitive tasks will be standardised to allow an overall score of global cognitive function to be calculated)
Change from baseline (pre intervention) to week 24 (post intervention)
Change in Cognitive Performance (0-36 weeks)
Time Frame: Change from baseline (pre intervention) to week 36 (follow-up)
Composite measure of global cognitive function (scores from different cognitive tasks will be standardised to allow an overall score of global cognitive function to be calculated)
Change from baseline (pre intervention) to week 36 (follow-up)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Flow Mediated Dilatation (0-24 weeks)
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Technique to measure the flexibility of the endothelium in larger peripheral blood vessels
Change from baseline (pre intervention) to week 24 (post intervention)
Change in Flow Mediated Dilatation (0-36 weeks)
Time Frame: Change from baseline (pre intervention) to week 36 (follow-up)
Technique to measure the flexibility of the endothelium in larger peripheral blood vessels
Change from baseline (pre intervention) to week 36 (follow-up)
Change in cerebral blood flow (0-24 weeks)
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Use of arterial spin labelling to determine cerebral blood flow at rest
Change from baseline (pre intervention) to week 24 (post intervention)
Change in cerebral blood flow (0-36 weeks)
Time Frame: Change from baseline (pre intervention) to week 36 (post intervention)
Use of arterial spin labelling to determine cerebral blood flow at rest
Change from baseline (pre intervention) to week 36 (post intervention)
Change in brain activity (0-24 weeks)
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Use of functional MRI to determine BOLD response (indicative of brain activation) during cognitive activity
Change from baseline (pre intervention) to week 24 (post intervention)
Change in brain activity (0-36 weeks)
Time Frame: Change from baseline (pre intervention) to week 36 (post intervention)
Use of functional MRI to determine BOLD response (indicative of brain activation) during cognitive activity
Change from baseline (pre intervention) to week 36 (post intervention)
Change in brain structure (0-24 weeks)
Time Frame: Change from baseline (pre intervention) to week 24 (follow-up)
Use of high resolution images to determine changes to brain structure such as grey and white matter
Change from baseline (pre intervention) to week 24 (follow-up)
Change in brain structure (0-36 weeks)
Time Frame: Change from baseline (pre intervention) to week 36 (follow-up)
Use of high resolution images to determine changes to brain structure such as white and grey matter
Change from baseline (pre intervention) to week 36 (follow-up)
Change in flavanol monomer levels
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of epicatechin and catechin in plasma and urine samples
Change from baseline (pre intervention) to week 24 (post intervention)
Change in procyanidin levels
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of procyanidin dimers through to decamers in plasma and urine samples
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of flavanol monomer metabolites/derivatives
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of epicatechin and catechin metabolites/derivatives in plasma and urine samples
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of procyanidin metabolites/derivatives
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of procyanidin metabolites/derivatives in plasma and urine samples
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of nitroso compounds
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of nitric oxide, nitrate and nitrite levels in plasma/serum &/ urine
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of markers of inflammation
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of pro and anti-inflammatory cytokines and C-reactive protein (CRP) levels in plasma/serum
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of markers of neuronal function
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of brain-derived neurotrophic factor (BDNF) and lactate in plasma/serum
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of a marker of stress/anxiety
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of cortisol in plasma/serum
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of a marker of oxidative stress
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of uric acid in plasma/serum
Change from baseline (pre intervention) to week 24 (post intervention)
Change in levels of markers of vascular function/cardiovascular disease (CVD) risk
Time Frame: Change from baseline (pre intervention) to week 24 (post intervention)
Concentrations of glucose, insulin, cholesterol (total, high density lipoprotein [HDL], low density lipoprotein [LDL]), non-esterified fatty acids [NEFA], triglycerides [TAG] in plasma/serum
Change from baseline (pre intervention) to week 24 (post intervention)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Reading

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Biotechnology and Biological Sciences Research Council
Mars, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 7, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2017

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 24, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UREC1548_CoCo_ChronicTrial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

To achieve the aim of data sharing with the wider community data will be submitted for inclusion in the Biotechnology and Biological Sciences Research Council (BBSRC)-funded Code Analysis, Repository & Modelling for E-Neuroscience (CARMEN) depository for neurophysiological datasets (http://www.carmen.org.uk). Data will also be accessible by making a direct request to the PI, and will be transferred to the recipient. Publications will be in open access journals where possible. If not possible, due to the need to reach the widest possible audience, pre-publication manuscripts arising from the project will be deposited in the free and publicly searchable University of Reading research database (CentAUR: http://centaur.reading.ac.uk). All data will be made available in an anonymised format upon request following publication of main findings. It is envisaged that the entire datasets will be available 6 months following the end of the project and maintained for a period of at least 10 years.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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