Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001053516
Ethics application status
Approved
Date submitted
16/09/2015
Date registered
7/10/2015
Date last updated
9/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The Cognitive Ageing Nutrition and Neurogenesis (CANN) trial: investigating the effects of a flavonoid/fatty acid supplement on cognitive function
Scientific title
A Randomised Controlled Trial in older adults with mild cognitive or memory impairment, 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] 287211 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 295805 0
Subjective Memory Impairment 295806 0
Condition category
Condition code
Alternative and Complementary Medicine 296068 296068 0 0
Other alternative and complementary medicine
Neurological 296560 296560 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fatty acid/flavonoid blend.
Daily (for 12 months) ingestion of study product containing 1.5g EPA + DHA, and 550mg of cocoa flavanols, provided as a cocoa extract. Compliance will be monitored using daily study food logs completed by the participant after taking their study treatments, along with counting the number of returned treatments at each study session.

A sub-group of 20 participants were not administered any intervention (active or placebo) and completed only the baseline measures, including neuroimaging measures. These participants were healthy controls with no memory complaints or cognitive impairment.
Intervention code [1] 292495 0
Treatment: Other
Comparator / control treatment
Placebo
Daily (for 12 months) ingestion of placebo oil and a cocoa extract
Control group
Placebo

Outcomes
Primary outcome [1] 295742 0
Number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System. This is a measure of cognitive function.
Timepoint [1] 295742 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [1] 316385 0
To investigate whether study food has beneficial effects on brain structure and volume (and in particular the hippocampus, which is the main brain region associated with age related cognitive decline). This is assessed using MRI.
Timepoint [1] 316385 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [2] 316386 0
Assess the impact of intervention on gut microflora speciation. Gut microflora speciation assessed by faecal sample.
Timepoint [2] 316386 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [3] 316387 0
Examine response to treatment according to baseline APOE status. APOE is assessed using a serum assay.
Timepoint [3] 316387 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [4] 316388 0
Establish the impact of intervention on 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] 316388 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [5] 316389 0
Examine the effect of intervention on executive function (cognitive domain) as measured by the CDR battery and other validated instruments.
Timepoint [5] 316389 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [6] 317698 0
Establish the impact of intervention on circulating biomarkers of cardiovascualr health.
Biomarkers to include BDNF, ß-amyloid, plasma lipids, inflammatory markers, nitric oxide and fatty acids, flavonoids and their metabolites (plasma and urine)
Timepoint [6] 317698 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [7] 317699 0
To investigate whether study food has beneficial effects on brain chemistry. This is assessed by MRI MRS scan.
Timepoint [7] 317699 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [8] 317700 0
To investigate whether study food has beneficial effects on cerebrovascular (brain) blood flow. This is assessed by MRI.
Timepoint [8] 317700 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [9] 317701 0
Assess the impact of intervention on gut microflora metabolism. Gut microflora metabolism assessed by faecal sample.
Timepoint [9] 317701 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [10] 317702 0
Examine response to treatment according to baseline BDNF status. BDNF status is measured from a blood serum assay.
Timepoint [10] 317702 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [11] 317703 0
Examine the impact of intervention on language (cognitive domain) as measured on the CDR battery and other validated instruments
Timepoint [11] 317703 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [12] 317704 0
Examine the impact of intervention on visuospatial function (cognitive domain) as measured on the CDR battery and other validated instruments
Timepoint [12] 317704 0
at baseline and at 12 months post commencement of intervention
Secondary outcome [13] 317705 0
Examine the impact of intervention on attention (cognitive domain) as measured by the CDR battery and other validated instruments
Timepoint [13] 317705 0
at baseline and at 12 months post commencement of intervention

Eligibility
Key inclusion criteria
For main study:
Male and female, aged 55 years and over
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

For healthy controls sub-study:
The same inclusion criteria apply except that participants must not have MCI or SMI
Minimum age
55 Years
Maximum age
No limit
Sex
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
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
In the main study, participants will be randomised to the intervention or control group centrally according to a computer-generated randomisation code. Eligible, recruited participants will be randomly assigned a participant number. The participant will receive the treatment that has been allocated to that participant number.
In the sub-study of healthy controls, only baseline assessments were conducted and participants did not receive any intervention or placebo in this sub-study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Statified allocation based on MCI/SMI status, APOE genotype status, and gender
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering 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
Efficacy
Statistical methods / analysis
Fatty acids: The most relevant study administered 1.3 g DHA and 450 mg EPA for 12 month to MCI (effects sizes are estimated from partial etas): Delayed recall:?p2 = 0.121 (Approx. d = 0.74); Digit span: partial eta=.254 (Approx. d = 1.17); Visual reproduction: partial eta=0.114 (Approx. d = 0.72). Computed d for the composite memory score (presented as z-score) was 1.17.
Flavonoids: Desideri et al (2012) administered 990 mg and 520 mg flavanols and reported an effect size (Cohen’s d of 1.64 for the lower dose). The outcome was a composite cognitive score. Krikorian et al (2010; 2012) used concord grape juice in MCI. They reported effect sizes (in this case Cohen f) of 0.28 for verbal learning and 0.33 for delayed recall – i.e. medium effect sizes.
Based on the range of effect sizes above, we would err on the side of caution and base a Power calculation on a medium effect size – i.e. Cohen’s d of approximately 0.5, which generates a sample size of 108/group for a two-arm trial with 90 power to detect a significant change at the 5% probability level. The group sizes assume a 20% attrition rate as found in past studies. In exercise interventions, the volume of the hippocampus, changes in Fractional Anisotropy measures from DTI scans, and the concentration of N-acetyl-aspartate from MR spectroscopy scans, have been observed with 120, 70, 137 participants, respectively. Based on this work, we expect that a sample size of 120 per group will be sufficient to observe age-related declines in MRI measures, and to learn whether these are offset by the intervention.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/11/2015
Actual
21/03/2016
Date of last participant enrolment
Anticipated
Actual
27/04/2018
Date of last data collection
Anticipated
Actual
30/04/2018
Sample size
Target
240
Accrual to date
Final
220
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 10059 0
3122 - Hawthorn
Recruitment outside Australia
Country [1] 7077 0
United Kingdom
State/province [1] 7077 0
Norwich

Funding & Sponsors
Funding source category [1] 291785 0
University
Name [1] 291785 0
University of Illinois
Country [1] 291785 0
United States of America
Primary sponsor type
University
Name
Swinburne Univeristy
Address
Centre for Human Psychopharmacology
Swinburne University of Technology
427-457 Burwood Rd,
Hawthorn VIC, 3122
Country
Australia
Secondary sponsor category [1] 290449 0
None
Name [1] 290449 0
Address [1] 290449 0
Country [1] 290449 0
Other collaborator category [1] 278572 0
University
Name [1] 278572 0
University of East Anglia
Address [1] 278572 0
Department of Nutrition
University of East Anglia
Floor 2, Bob Champion Research and Educational Building
James Watson Rd
Norwich, Norfolk NR4 7TJ
Country [1] 278572 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293304 0
Bellberry Limited
Ethics committee address [1] 293304 0
Ethics committee country [1] 293304 0
Australia
Date submitted for ethics approval [1] 293304 0
Approval date [1] 293304 0
21/07/2015
Ethics approval number [1] 293304 0
2015-03-227

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59306 0
Prof Andrew Scholey
Address 59306 0
Centre for Human Psychopharmacology
Swinburne University of Technology
427-457 Burwood Rd
Hawthorn VIC 3122
Country 59306 0
Australia
Phone 59306 0
+61 3 92148932
Fax 59306 0
Email 59306 0
[email protected]
Contact person for public queries
Name 59307 0
Renee Rowsell
Address 59307 0
Centre for Human Psychopharmacology
Swinburne University of Technology
427-457 Burwood Rd
Hawthorn VIC 3122
Country 59307 0
Australia
Phone 59307 0
+61 3 92145656
Fax 59307 0
Email 59307 0
[email protected]
Contact person for scientific queries
Name 59308 0
Andrew Scholey
Address 59308 0
Centre for Human Psychopharmacology
Swinburne University of Technology
427-457 Burwood Rd
Hawthorn VIC 3122
Country 59308 0
Australia
Phone 59308 0
+61 3 92148932
Fax 59308 0
Email 59308 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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