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The Impact of Cranberries On the Microbiome and the Brain in Healthy Ageing sTudy (COMBAT) (COMBAT)

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ClinicalTrials.gov Identifier: NCT03679533
Recruitment Status : Recruiting
First Posted : September 20, 2018
Last Update Posted : January 24, 2019
Sponsor:
Collaborator:
Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
Information provided by (Responsible Party):
University of East Anglia

Brief Summary:

Tremendous progress has been made in characterizing the interactions between the central nervous system and the gastrointestinal tract. This concept of a gut-brain axis suggests that influencing bacteria in the gut is a promising approach for developing new ways of benefiting brain function. This is particularly relevant for an ageing population for which cognitive decline is a common symptom and can be an indicator for the development of neurodegenerative conditions such as dementia. There is good evidence already that nutrition can delay the development of cognitive decline in ageing, in particular for ageing-sensitive brain regions such as the medial temporal lobe, however this has been little explored for cranberry intake. Cranberries are high in plant-derived nutrients called polyphenols, which have been suggested to promote brain function and protect against disease-causing mechanisms. In the proposed project we will pioneer work to investigate the impact of cranberry intake on gut bacteria and how it relates to cognitive performance in ageing and associated regions in the brain.

This study is being conducted by Chief Investigators Dr David Vauzour and Prof Michael Hornberger at the University of East Anglia. Sixty participants (i.e. n=30 control and treatment groups) aged 50-80 years old, with no memory complaints will be recruited for this 12-week double-blind placebo-controlled parallel intervention of cranberry flavonoids. Freeze-dried cranberry or a matched placebo will be taken twice daily for the duration of the trial. Blood, urine and faecal samples will be collected for microbiome, DNA, biochemical and nutritional analysis. Participants will also undergo cognitive testing, as well as MRI scanning to detect changes in brain physiology.


Condition or disease Intervention/treatment Phase
Aging Cognitive Decline Dietary Supplement: Freeze-Dried Cranberry Powder Dietary Supplement: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind placebo-controlled parallel intervention
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Impact of Cranberries on the Microbiome and the Brain in Healthy Ageing: A Feasibility Intervention
Actual Study Start Date : October 2, 2018
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : December 31, 2019

Arm Intervention/treatment
Active Comparator: Active Cranberry Study Food Dietary Supplement: Freeze-Dried Cranberry Powder
Freeze-dried cranberry powder (or matched placebo), approximating 500mg active flavonoids per day, taken twice daily for 12 weeks.

Placebo Comparator: Placebo Study Food Dietary Supplement: Placebo
Placebo food powder matched for taste, colour, energy and macronutrient content to the active cranberry powder.




Primary Outcome Measures :
  1. Gut microflora speciation and metabolism [ Time Frame: 12 weeks ]
    Measured in faecal and serum samples.

  2. Change in volumes of hippocampus and other key brain structures [ Time Frame: 12 weeks ]
    Structural magnetic resonance imaging

  3. Change in cerebrovascular blood flow [ Time Frame: 12 weeks ]
    Measured using spectroscopy

  4. Change in global cognition [ Time Frame: 12 weeks ]
    Global cognition to be measured using the Addenbrooke's Cognitive Examination - III, from 0-100, with higher scores indicating better global cognitive performance.

  5. Change in spatial navigation abilities [ Time Frame: 12 weeks ]
    The Supermarket Test, with outcomes including accurate reporting of starting direction, and accurate indication of end position and direction.

  6. Change in executive function and attention [ Time Frame: 12 weeks ]
    Trail Making Test, with scores including time taken to complete and number of errors made.

  7. Change in memory performance [ Time Frame: 12 weeks ]
    The Rey Complex Figure Test, with outcomes including time taken to complete copy, accuracy out of a possible 36 of copy and accuracy out of 36 of 3-minute recall.

  8. Change in spatial navigation abilities [ Time Frame: 12 weeks ]
    SeaHero Quest Test, with outcomes including time taken to complete, accuracy of path taken and number of errors made.

  9. Change in executive function and attention [ Time Frame: 12 Weeks ]
    Digit Span Backwards, scored out of a possible 14 for numbers recited backwards in the correct order.

  10. Change in presence of circulating inflammatory biomarkers (hs-CRP) [ Time Frame: 12 weeks ]
    Blood samples analysed for presence of inflammatory cytokines

  11. Change in circulating biomarkers of neuronal functioning and cognitive decline (BDNF) [ Time Frame: 12 weeks ]
    Blood samples analysed for presence of circulating biomarkers of neural function

  12. Change in circulating biomarkers of lipid metabolism (total-, HDL-, LDL-cholesterol) [ Time Frame: 12 weeks ]
    Blood samples analysed for presence of circulating biomarkers of lipid metabolism

  13. Change in circulating biomarkers of lipid metabolism (triglycerides) [ Time Frame: 12 weeks ]
    Blood samples analysed for presence of circulating biomarkers of lipid metabolism


Secondary Outcome Measures :
  1. Changes in energy expenditure and sleep [ Time Frame: 12 weeks ]
    Actigraphs to be used to measure changes in activity and sleep patterns of participants.

  2. Genetics related to neurodegenerative disease [ Time Frame: Baseline ]
    Blood samples to be analysed for genes associated with neurodegenerative disease and dementia (eg. C9ORF72, APOE-4)

  3. Biomarkers of gut permability and endotoxemia (LPS) [ Time Frame: 12 weeks ]
    Blood serum/plasma samples to be analysed for presence of lipopolysaccharide (LPS) as a biomarker of gut permability and possible endotoxemia

  4. Levels of sunlight exposure [ Time Frame: Baseline, Follow-up ]
    Self-reported levels of daily sunlight exposure to be measured using a brief questionnaire



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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged between 50 and 80 years old.
  • Willing and able to provide written informed consent.
  • Fluent in written and spoken English.
  • Normal or corrected to normal vision and hearing.
  • Understands and is willing and able to comply with all study procedures.

Exclusion Criteria:

  • Diagnosis of any form of dementia or significant neurological condition.
  • Significant memory complaints.
  • Past history or MRI evidence of brain damage, including significant trauma, stroke, learning difficulties or serious neurological disorder, including a loss of consciousness for more than 24 hours.
  • Currently smoking or ceased smoking less than 6 months ago.
  • Chronic fatigue syndrome, liver disease, diabetes mellitus, or gall bladder abnormalities.
  • History of alcohol or drug dependency.
  • Clinically diagnosed psychiatric disorder.
  • Existing diagnosed gastrointestinal disorders likely to impact on absorption of flavonoids.
  • Known allergy to the intervention supplement.
  • Any significant medical condition likely to affect participation.
  • Currently a participant or have been a participant in any other study involving an investigational product within the last 4 weeks.
  • Uncontrolled hypertension (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg).
  • Major cardiovascular event, such as myocardial infarction, within the last 12 months.
  • On a stable prescription of blood pressure lowering medication or non-steroidal anti-inflammatory drugs. for fewer than 2 months.
  • Prescribed anti-coagulant/blood thinning medication (eg. warfarin).
  • Taking flavonoid containing supplements (and unwilling to cease intake during, and 1 month preceding the trial) or unwilling to maintain existing intake of other supplements.
  • High flavonoid intake defined as > 15 portions of flavonoid rich foods per day
  • Are currently taking medication or supplements which have a significant impact on the outcome measures.

In addition, any participants with claustrophobia will not be invited to participate in the neuroimaging component of the study. Likewise for metal implants, e.g. pacemaker that precludes MRI.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03679533


Contacts
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Contact: Emma Flanagan, BSc +44 1603591623 e.flanagan@uea.ac.uk
Contact: David Vauzour, PhD +441603591732 d.vauzour@uea.ac.uk

Locations
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United Kingdom
University of East Anglia Recruiting
Norwich, Norfolk, United Kingdom, NR4 7UQ
Contact: Emma Flanagan, BSc    +4401603591623    e.flanagan@uea.ac.uk   
Sponsors and Collaborators
University of East Anglia
Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
Investigators
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Principal Investigator: David Vauzour, PhD University of East Anglia
Principal Investigator: Michael Hornberger, PhD University of East Anglia

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Responsible Party: University of East Anglia
ClinicalTrials.gov Identifier: NCT03679533     History of Changes
Other Study ID Numbers: R204719
First Posted: September 20, 2018    Key Record Dates
Last Update Posted: January 24, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of East Anglia:
Cognition
Ageing
Nutrition
Microbiome
Flavonoids

Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders