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

Mental Processes Clinical Trial

— CoCo_Chronic  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03030053
• Other study ID #: UREC1548_CoCo_ChronicTrial
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2016
• Est. completion date: December 2018

Study information

• Verified date: May 2018
• Source: University of Reading
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mental Processes

Intervention

Dietary Supplement:
• Cocoa-Flavanol Supplements
3 capsules each containing 300mg cocoa flavanols (total daily dose of 900mg cocoa-flavanols).
• Control Supplements
3 capsules each containing 0mg cocoa-flavanols

Locations

Country	Name	City	State
United Kingdom	Hugh Sinclair Unit of Human Nutrition, University of Reading	Reading	Berkshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Reading	Biotechnology and Biological Sciences Research Council, Mars, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cognitive Performance (0-24 weeks)	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)
Primary	Change in Cognitive Performance (0-36 weeks)	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	Change in Flow Mediated Dilatation (0-24 weeks)	Technique to measure the flexibility of the endothelium in larger peripheral blood vessels	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in Flow Mediated Dilatation (0-36 weeks)	Technique to measure the flexibility of the endothelium in larger peripheral blood vessels	Change from baseline (pre intervention) to week 36 (follow-up)
Secondary	Change in cerebral blood flow (0-24 weeks)	Use of arterial spin labelling to determine cerebral blood flow at rest	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in cerebral blood flow (0-36 weeks)	Use of arterial spin labelling to determine cerebral blood flow at rest	Change from baseline (pre intervention) to week 36 (post intervention)
Secondary	Change in brain activity (0-24 weeks)	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)
Secondary	Change in brain activity (0-36 weeks)	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)
Secondary	Change in brain structure (0-24 weeks)	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)
Secondary	Change in brain structure (0-36 weeks)	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)
Secondary	Change in flavanol monomer levels	Concentrations of epicatechin and catechin in plasma and urine samples	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in procyanidin levels	Concentrations of procyanidin dimers through to decamers in plasma and urine samples	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of flavanol monomer metabolites/derivatives	Concentrations of epicatechin and catechin metabolites/derivatives in plasma and urine samples	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of procyanidin metabolites/derivatives	Concentrations of procyanidin metabolites/derivatives in plasma and urine samples	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of nitroso compounds	Concentrations of nitric oxide, nitrate and nitrite levels in plasma/serum &/ urine	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of markers of inflammation	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)
Secondary	Change in levels of markers of neuronal function	Concentrations of brain-derived neurotrophic factor (BDNF) and lactate in plasma/serum	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of a marker of stress/anxiety	Concentrations of cortisol in plasma/serum	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of a marker of oxidative stress	Concentrations of uric acid in plasma/serum	Change from baseline (pre intervention) to week 24 (post intervention)
Secondary	Change in levels of markers of vascular function/cardiovascular disease (CVD) risk	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)