The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02525198




Registration number
NCT02525198
Ethics application status
Date submitted
11/05/2015
Date registered
17/08/2015
Date last updated
18/11/2016

Titles & IDs
Public title
The Cognitive Ageing Nutrition and Neurogenesis (CANN) Trial
Scientific title
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
Secondary ID [1] 0 0
R21647
Universal Trial Number (UTN)
Trial acronym
CANN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 0 0
Subjective Memory Impairment 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - fatty acid/flavonoid blend
Other interventions - Placebo

Placebo Comparator: Placebo - Placebo group: 12 month daily ingestion of placebo oil and flavonoid-poor matched extract

Experimental: fatty acid/flavonoid blend - Experimental group: 12 month daily ingestion of 1.5 g EPA+DHA and 500 mg flavonoids


Other interventions: fatty acid/flavonoid blend
see arm description

Other interventions: Placebo
see arm description

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Hippocampal volume - To be measured on magnetic resonance imaging
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Circulating biomarkers of cognition - Biomarkers to include BDNF, ß-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Circulating biomarkers of cardiovascular health - Biomarkers to include BDNF, ß-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Language ability on the Boston Naming Test - Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Attention ability on the Digit Span task - Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Executive function on the Trail Making Task - Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Cerebrovascular blood flow - To be measured on spectroscopy
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
8 minutes

Eligibility
Key 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
Minimum age
55 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Centre for Human Psychopharmacology, Swinburne Univerity of Technology - Melbourne
Recruitment postcode(s) [1] 0 0
3122 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Norfolk

Funding & Sponsors
Primary sponsor type
Other
Name
University of East Anglia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Swinburne University of Technology
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Illinois at Chicago
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/show/NCT02525198
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anne Marie Minihane, PhD
Address 0 0
Department of Nutrition, University of East Anglia, Norwich, U.K.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anne Marie Minihane, PhD
Address 0 0
Country 0 0
Phone 0 0
+44-1603592389
Fax 0 0
Email 0 0
a.minihane@uea.ac.uk
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02525198