NCT03679533

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Oct 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 15, 2018

Completed
3 months until next milestone

First Posted

Study publicly available on registry

September 20, 2018

Completed
12 days until next milestone

Study Start

First participant enrolled

October 2, 2018

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 22, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 22, 2020

Completed
Last Updated

September 30, 2020

Status Verified

September 1, 2020

Enrollment Period

1.6 years

First QC Date

June 15, 2018

Last Update Submit

September 29, 2020

Conditions

AgingCognitive Decline

Keywords

CognitionAgeingNutritionMicrobiomeFlavonoids

Outcome Measures

Primary Outcomes (13)

  • Gut microflora speciation and metabolism

    Measured in faecal and serum samples.

    12 weeks

  • Change in volumes of hippocampus and other key brain structures

    Structural magnetic resonance imaging

    12 weeks

  • Change in cerebrovascular blood flow

    Measured using spectroscopy

    12 weeks

  • Change in global cognition

    Global cognition to be measured using the Addenbrooke's Cognitive Examination - III, from 0-100, with higher scores indicating better global cognitive performance.

    12 weeks

  • Change in spatial navigation abilities

    The Supermarket Test, with outcomes including accurate reporting of starting direction, and accurate indication of end position and direction.

    12 weeks

  • Change in executive function and attention

    Trail Making Test, with scores including time taken to complete and number of errors made.

    12 weeks

  • Change in memory performance

    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.

    12 weeks

  • Change in spatial navigation abilities

    SeaHero Quest Test, with outcomes including time taken to complete, accuracy of path taken and number of errors made.

    12 weeks

  • Change in executive function and attention

    Digit Span Backwards, scored out of a possible 14 for numbers recited backwards in the correct order.

    12 Weeks

  • Change in presence of circulating inflammatory biomarkers (hs-CRP)

    Blood samples analysed for presence of inflammatory cytokines

    12 weeks

  • Change in circulating biomarkers of neuronal functioning and cognitive decline (BDNF)

    Blood samples analysed for presence of circulating biomarkers of neural function

    12 weeks

  • Change in circulating biomarkers of lipid metabolism (total-, HDL-, LDL-cholesterol)

    Blood samples analysed for presence of circulating biomarkers of lipid metabolism

    12 weeks

  • Change in circulating biomarkers of lipid metabolism (triglycerides)

    Blood samples analysed for presence of circulating biomarkers of lipid metabolism

    12 weeks

Secondary Outcomes (4)

  • Changes in energy expenditure and sleep

    12 weeks

  • Genetics related to neurodegenerative disease

    Baseline

  • Biomarkers of gut permability and endotoxemia (LPS)

    12 weeks

  • Levels of sunlight exposure

    Baseline, Follow-up

Study Arms (2)

Active Cranberry Study Food

ACTIVE COMPARATOR
Dietary Supplement: Freeze-Dried Cranberry Powder

Placebo Study Food

PLACEBO COMPARATOR
Dietary Supplement: Placebo

Interventions

Freeze-Dried Cranberry PowderDIETARY_SUPPLEMENT

Freeze-dried cranberry powder (or matched placebo), approximating 500mg active flavonoids per day, taken twice daily for 12 weeks.

Active Cranberry Study Food
PlaceboDIETARY_SUPPLEMENT

Placebo food powder matched for taste, colour, energy and macronutrient content to the active cranberry powder.

Placebo Study Food

Eligibility Criteria

Age50 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of East Anglia

Norwich, Norfolk, NR4 7UQ, United Kingdom

Location

Related Publications (1)

  • Flanagan E, Cameron D, Sobhan R, Wong C, Pontifex MG, Tosi N, Mena P, Del Rio D, Sami S, Narbad A, Muller M, Hornberger M, Vauzour D. Chronic Consumption of Cranberries (Vaccinium macrocarpon) for 12 Weeks Improves Episodic Memory and Regional Brain Perfusion in Healthy Older Adults: A Randomised, Placebo-Controlled, Parallel-Groups Feasibility Study. Front Nutr. 2022 May 19;9:849902. doi: 10.3389/fnut.2022.849902. eCollection 2022.

    PMID: 35662954DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental Disorders

Study Officials

  • David Vauzour, PhD

    University of East Anglia

    PRINCIPAL INVESTIGATOR

  • Michael Hornberger, PhD

    University of East Anglia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Double-blind placebo-controlled parallel intervention
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 15, 2018

First Posted

September 20, 2018

Study Start

October 2, 2018

Primary Completion

May 22, 2020

Study Completion

May 22, 2020

Last Updated

September 30, 2020

Record last verified: 2020-09

Locations

GB(1)