Mild Cognitive ImpairmentCANNNCT02525198
The Cognitive Ageing Nutrition and Neurogenesis (CANN) Trial
A study testing fatty acid/flavonoid blend in people with Mild Cognitive Impairment and Subjective Memory Impairment, run by University of East Anglia at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Subjective Memory Impairment
- What is being tested?
- fatty acid/flavonoid blend
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 259 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 1 Aug 2015to 31 Mar 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
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- Normal, or corrected to normal vision and hearing
- Right handed, for MRI
- Stable use of any prescribed medication for at least four weeks
Who cannot join
- 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)
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- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
Beckman Institute, University of Illinois
Urbana, Illinois, 61801
Australia1 site
Centre for Human Psychopharmacology, Swinburne Univerity of Technology
Melbourne, Victoria, 3122
United Kingdom1 site
Department of Nutrition, University of East Anglia
Norwich, Norfolk, NR4 7TJ
About this study
Official 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
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).
Read the 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).
- Being tested
- fatty acid/flavonoid blend, Placebo
- Keywords
- Mild cognitive impairment, Subjective memory impairment, Dementia, Flavonoids, Fatty acids, Cognition, Gut microflora
- Medical subject headings
- Cognitive Dysfunction, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fatty acid/flavonoid blendDietary supplement
see arm description
PlaceboDietary supplement
see arm description
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo group: 12 month daily ingestion of placebo oil and flavonoid-poor matched extract Receives: Dietary Supplement: Placebo |
| fatty acid/flavonoid blend | Experimental | Experimental group: 12 month daily ingestion of 1.5 g EPA+DHA and 500 mg flavonoids Receives: Dietary Supplement: fatty acid/flavonoid blend |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (11)
Hippocampal volume
To be measured on magnetic resonance imaging
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 12 months
Language ability on the Boston Naming Test
Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)
Measured: 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)
Measured: 12 months
Attention ability on the Digit Span task
Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)
Measured: 12 months
Executive function on the Trail Making Task
Allows for categorization according to cognitive status (mild cognitive impairment, dementia, subjective memory impairment)
Measured: 12 months
Cerebrovascular blood flow
To be measured on spectroscopy
Measured: 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.
Measured: 8 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study start1 Aug 2015
- Primary completion31 Mar 2018
- Study completion31 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Collaborators
- Swinburne University of Technology, University of Illinois Chicago
- Responsible party
- Sponsor
- Investigators
- Anne Marie Minihane, PhD, Principal investigator, Department of Nutrition, University of East Anglia, Norwich, U.K.Andrew Scholey, PhD, Principal investigator, Centre for Human Psychopharmacology, Swinburne University of TechnologyNeal J Cohen, PhD, Principal investigator, Beckman Institute, University of Illinois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02525198
- Sponsor's protocol ID
- R21647
- Acronym
- CANN
- Status last verified
- Nov 2023
- First submitted
- 11 May 2015
- Last updated
- 14 May 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Vauzour D, Scholey A, White DJ, Cohen NJ, Cassidy A, Gillings R, Irvine MA, Kay CD, Kim M, King R, Legido-Quigley C, Potter JF, Schwarb H, Minihane AM. A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study. Am J Clin Nutr. 2023 Aug;118(2):369-381. doi: 10.1016/j.ajcnut.2023.06.008. Epub 2023 Jun 12.
PubMed 37315924Irvine 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.
PubMed 30426067
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02525198
- Acronym / sponsor ID
- CANN / R21647
- Keywords
- Mild cognitive impairment, Subjective memory impairment, Dementia, Flavonoids, Fatty acids, Cognition, Gut microflora
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 259 participants (actual)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Collaborators
- Swinburne University of Technology, University of Illinois Chicago
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo group: 12 month daily ingestion of placebo oil and flavonoid-poor matched extract |
| fatty acid/flavonoid blend | Experimental | Dietary Supplement: fatty acid/flavonoid blendExperimental group: 12 month daily ingestion of 1.5 g EPA+DHA and 500 mg flavonoids |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fatty acid/flavonoid blendsee arm description | Dietary supplement | fatty acid/flavonoid blend |
| Placebosee arm description | Dietary supplement | Placebo |
Primary outcome
Number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System
Time frame: 12 months
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.
11 secondary outcomes
Hippocampal volume
Time frame: 12 months
Gut microflora speciation and metabolism
Time frame: 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
Time frame: 12 months
Circulating biomarkers of cognition
Time frame: 12 months
Circulating biomarkers of cardiovascular health
Time frame: 12 months
Language ability on the Boston Naming Test
Time frame: 12 months
Visuospatial ability on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Figure Copy test
Time frame: 12 months
Attention ability on the Digit Span task
Time frame: 12 months
Executive function on the Trail Making Task
Time frame: 12 months
Cerebrovascular blood flow
Time frame: 12 months
Measurement of blood brain barrier permeability
Time frame: 8 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- Derived from this study: PubMed 37315924Vauzour D, Scholey A, White DJ, Cohen NJ, Cassidy A, Gillings R, Irvine MA, Kay CD, Kim M, King R, Legido-Quigley C, Potter JF, Schwarb H, Minihane AM. A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study. Am J Clin Nutr. 2023 Aug;118(2):369-381. doi: 10.1016/j.ajcnut.2023.06.008. Epub 2023 Jun 12.
- Derived from this study: PubMed 30426067Irvine 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Marie Minihane, PhD principal investigator
Department of Nutrition, University of East Anglia, Norwich, U.K.
Andrew Scholey, PhD principal investigator
Centre for Human Psychopharmacology, Swinburne University of Technology
Neal J Cohen, PhD principal investigator
Beckman Institute, University of Illinois
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing fatty acid/flavonoid blend in people with Mild Cognitive Impairment and Subjective Memory Impairment, run by University of East Anglia at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of false positive responses during the picture recognition task of the CDR Computerized Cognitive Assessment System (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02525198, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.