The Cognitive Ageing Nutrition and Neurogenesis (CANN) Trial (CANN)

A Randomised Controlled Trial in 'At Risk' Humans Investigating the Cognitive Benefits of a Combined Flavonoid/Fatty Acid Intervention and Underlying Mechanisms of Action: The COGNITIVE AGING NUTRITION and NEUROGENESIS (CANN) Trial

There is a dearth of research which takes a multi-compound approach to dietary interventions, in humans, aimed at improving outcome measures of cognition. Animal research in particular points towards fatty acids and flavonoids having a potentiating effect on each other, and possibly even being synergistic. Thus, study products will be administered in the present trial comprising both of these compounds, with a view to investigating their potential effects on cognition in older adults with mild cognitive impairment (MCI) or subjective memory impairment (SMI).

Study Overview

• Status: Unknown
• Conditions: Mild Cognitive Impairment; Subjective Memory Impairment
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: fatty acid/flavonoid blend

Detailed Description

240 participants, aged 55 or above, will be recruited (120 Norwich, 120 Melbourne; to include both MCI and SCI participants).

Participants will be asked to take the study food each day for 12 months, and to come to the clinical assessment unit on 3 occasions, at baseline, 3 months and 12 months, to complete a cognitive task battery such that their performance may be investigated in the context of the intervention.

Urine, blood and faecal samples will be collected and magnetic resonance imaging (MRI) will be applicable to half of each population (i.e to 60 MCI and 60 SCI, 30 of each at Norwich and Melbourne).

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Marie Minihane, PhD; Phone Number: +44-1603592389; Email: A.Minihane@uea.ac.uk
• Study Contact Backup: Name: David Vauzour, PhD; Phone Number: +44-1603 591732; Email: D.Vauzour@uea.ac.uk

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3122
      • Not yet recruiting
      • Centre for Human Psychopharmacology, Swinburne Univerity of Technology
      • Contact: Andrew Scholey, PhD; Phone Number: +613 9214 8932; Email: ascholey@swin.edu.au
      • Principal Investigator: Andrew Scholey, PhD
• United Kingdom
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7TJ
      • Recruiting
      • Department of Nutrition, University of East Anglia
      • Contact: Anne Marie Minihane, PhD; Phone Number: +44-1603592389; Email: A.Minihane@uea.ac.uk
      • Principal Investigator: Anne Marie Minihane, PhD
• United States
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Not yet recruiting
      • Beckman Institute, University of Illinois
      • Contact: Neal J Cohen, PhD; Phone Number: 217-244-4339; Email: njc@illinois.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female, aged ≥ 55 years
• Mild cognitive impairment (MCI) or subjective memory impairment (SMI) with no indication of clinical dementia or depression
• Willing and able to provide written informed consent.
• Understands and is willing and able to comply with all study procedures.
• Fluent in written and spoken English.
• In good general health including blood biochemical, haematological and urinalysis within the normal range at screening (as judged by the clinical advisor)
• Normal, or corrected to normal vision and hearing
• Right handed, for MRI
• Stable use of any prescribed medication for at least four weeks

Exclusion Criteria:

• Diagnosis of Alzheimer's disease (AD) or other form of dementia or significant neurological disorder
• Parent or sibling who developed premature dementia <60y (suggestive of a familial monogenic form of cognitive decline)
• Past history or MRI evidence of brain damage including significant trauma, stroke, learning difficulties or serious neurological disorder, including loss of consciousness > 24 hours
• History of alcohol or drug dependency within the last 2 years
• Other clinically diagnosed psychiatric disorder likely to affect the cognitive measures (as judged by clinical adviser)
• Existing diagnosed gastrointestinal disorders likely to impact on absorption of flavonoids and fatty acids (as judged by clinical adviser)
• Major cardiovascular event, e.g. myocardial infarction or stroke, in the last 12 months
• Carotid stents or severe stenosis
• Known allergy to fish or any other component in the intervention supplements
• Existing medical conditions likely to affect the study measures (as judged by clinical adviser)
• Uncontrolled hypertension (Systolic Blood Pressure (SBP) >140mmHg, Diastolic Blood Pressure (DBP) >90mmHg)
• BMI >40kg/m2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo group: 12 month daily ingestion of placebo oil and flavonoid-poor matched extract	Dietary supplement: Placebo; see arm description
Experimental: fatty acid/flavonoid blend; Experimental group: 12 month daily ingestion of 1.5 g EPA+DHA and 500 mg flavonoids	Dietary supplement: fatty acid/flavonoid blend; see arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System	The CDR Computerized Cognitive Assessment System will be used to measure the cognitive effects of the treatments. The battery is sensitive to bidirectional cognitive change including trials in MCI, dementia and SMI. There is strong converging evidence that one particular aspect of performance, namely the number of false positive responses during a picture recognition task, is particularly sensitive to hippocampal integrity (based on activation of the dentate gyrus during the task, and specific decrements in conditions associated with poorer hippocampal function). This will form the primary outcome in this study.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippocampal volume	To be measured on magnetic resonance imaging	12 months
Gut microflora speciation and metabolism	Measured in faecal samples. By extension, we also seek to consider the contribution of the microflora to cognition function and its response to treatment.	12 months
Association between baseline APOE status and number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System	We will assess the impact of intervention in respect to presence or absence of APOE 4 gene across participants, which is a risk factor for dementia.	12 months
Circulating biomarkers of cognition	Biomarkers to include BDNF, β-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)	12 months
Circulating biomarkers of cardiovascular health	Biomarkers to include BDNF, β-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)	12 months
Language ability on the Boston Naming Test	Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)	12 months
Visuospatial ability on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Figure Copy test	Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)	12 months
Attention ability on the Digit Span task	Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)	12 months
Executive function on the Trail Making Task	Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)	12 months
Cerebrovascular blood flow	To be measured on spectroscopy	12 months
Measurement of blood brain barrier permeability	Allows testing of the hypothesis that the test food will help improve BBB permeability through its action on endothelial function. Six axial slices will be measured every 1.34 seconds for 8 minutes.	8 minutes

Collaborators and Investigators

• Sponsor: University of East Anglia
• Collaborators: University of Illinois at Chicago; Swinburne University of Technology
• Investigators: Principal Investigator: Anne Marie Minihane, PhD, Department of Nutrition, University of East Anglia, Norwich, U.K.; Principal Investigator: Andrew Scholey, PhD, Centre for Human Psychopharmacology, Swinburne University of Technology; Principal Investigator: Neal J Cohen, PhD, Beckman Institute, University of Illinois

Publications and helpful links

General Publications

• Irvine MA, Scholey A, King R, Gillings R, Vauzour D, Demichele SJ, Das T, Wesnes KA, Sutton BP, Cassidy A, Pipingas A, Potter JF, Johnson G, White D, Larsen R, Cohen NJ, Minihane AM. The Cognitive Ageing, Nutrition and Neurogenesis (CANN) trial: Design and progress. Alzheimers Dement (N Y). 2018 Sep 5;4:591-601. doi: 10.1016/j.trci.2018.08.001. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: August 14, 2015
• First Posted (Estimate): August 17, 2015

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Dementia; Cognition; Mild cognitive impairment; Fatty acids; Flavonoids; Gut microflora; Subjective memory impairment
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: R21647