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

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ClinicalTrials.gov Identifier: NCT03030053
Recruitment Status : Unknown
Verified May 2018 by Jeremy Paul Edward Spencer, University of Reading.
Recruitment status was:  Active, not recruiting
First Posted : January 24, 2017
Last Update Posted : May 24, 2018
Sponsor:
Collaborators:
Mars, Inc.
Biotechnology and Biological Sciences Research Council
Information provided by (Responsible Party):
Jeremy Paul Edward Spencer, University of Reading

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Mental Processes Dietary Supplement: Cocoa-Flavanol Supplements Dietary Supplement: Control Supplements Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Mechanistic Assessment of the Acute and Chronic Cognitive Effects of Flavanol/Anthocyanin Intervention in Humans - Chronic Trial
Study Start Date : February 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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)

  2. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030053


Locations
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United Kingdom
Hugh Sinclair Unit of Human Nutrition, University of Reading
Reading, Berkshire, United Kingdom, RG6 5SG
Sponsors and Collaborators
University of Reading
Mars, Inc.
Biotechnology and Biological Sciences Research Council
Investigators
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Principal Investigator: Jeremy PE Spencer, PhD University of Reading
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Responsible Party: Jeremy Paul Edward Spencer, Professor of Nutritional Medicine, University of Reading
ClinicalTrials.gov Identifier: NCT03030053    
Other Study ID Numbers: UREC1548_CoCo_ChronicTrial
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Keywords provided by Jeremy Paul Edward Spencer, University of Reading:
Flavanols
Flavonoids
Polyphenols
Cognition
Aging