Clinical trial NCT03679533: The Impact of Cranberries On the Microbiome and the Brain in Healthy Ageing sTudy (COMBAT)
Official title: The Impact of Cranberries on the Microbiome and the Brain in Healthy Ageing: A Feasibility Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aging
Cognitive Decline
Keywords: Cognition
Ageing
Nutrition
Microbiome
Flavonoids
Lead sponsor: University of East Anglia
Sponsor class: OTHER
Collaborators: name: Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
First posted: 2018-09-20
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind placebo-controlled parallel intervention
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Gut microflora speciation and metabolism
timeFrame: 12 weeks
measure: Change in volumes of hippocampus and other key brain structures
timeFrame: 12 weeks
measure: Change in cerebrovascular blood flow
timeFrame: 12 weeks
measure: Change in global cognition
timeFrame: 12 weeks
measure: Change in spatial navigation abilities
timeFrame: 12 weeks
measure: Change in executive function and attention
timeFrame: 12 weeks
measure: Change in memory performance
timeFrame: 12 weeks
measure: Change in spatial navigation abilities
timeFrame: 12 weeks
measure: Change in executive function and attention
timeFrame: 12 Weeks
measure: Change in presence of circulating inflammatory biomarkers (hs-CRP)
timeFrame: 12 weeks
measure: Change in circulating biomarkers of neuronal functioning and cognitive decline (BDNF)
timeFrame: 12 weeks
measure: Change in circulating biomarkers of lipid metabolism (total-, HDL-, LDL-cholesterol)
timeFrame: 12 weeks
measure: Change in circulating biomarkers of lipid metabolism (triglycerides)
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in energy expenditure and sleep
timeFrame: 12 weeks
measure: Genetics related to neurodegenerative disease
timeFrame: Baseline
measure: Biomarkers of gut permability and endotoxemia (LPS)
timeFrame: 12 weeks
measure: Levels of sunlight exposure
timeFrame: Baseline, Follow-up
Other outcomes:
Locations:
city: Norwich
country: United Kingdom
facility: University of East Anglia
state: Norfolk
Study officials:
affiliation: University of East Anglia
name: David Vauzour, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of East Anglia
name: Michael Hornberger, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.