AgingCOMBATNCT03679533
The Impact of Cranberries On the Microbiome and the Brain in Healthy Ageing sTudy (COMBAT)
A study testing Freeze-Dried Cranberry Powder in people with Aging and Cognitive Decline, run by University of East Anglia at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Cognitive Decline
- What is being tested?
- Freeze-Dried Cranberry Powder
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Oct 2018to 22 May 2020
- 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 50 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of East Anglia
Norwich, Norfolk, NR4 7UQ
About this study
Official title: The Impact of Cranberries on the Microbiome and the Brain in Healthy Ageing: A Feasibility Intervention
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.
- Conditions
- Aging, Cognitive Decline
- Being tested
- Freeze-Dried Cranberry Powder, Placebo
- Keywords
- Cognition, Ageing, Nutrition, Microbiome, Flavonoids
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Freeze-Dried Cranberry PowderDietary supplement
Freeze-dried cranberry powder (or matched placebo), approximating 500mg active flavonoids per day, taken twice daily for 12 weeks.
PlaceboDietary supplement
Placebo food powder matched for taste, colour, energy and macronutrient content to the active cranberry powder.
| Study group | Role | What they receive |
|---|---|---|
| Active Cranberry Study Food | Active comparator | Not described Receives: Dietary Supplement: Freeze-Dried Cranberry Powder |
| Placebo Study Food | Placebo comparator | Not described Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gut microflora speciation and metabolism
Measured in faecal and serum samples.
Measured: 12 weeks
Change in volumes of hippocampus and other key brain structures
Structural magnetic resonance imaging
Measured: 12 weeks
Change in cerebrovascular blood flow
Measured using spectroscopy
Measured: 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.
Measured: 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.
Measured: 12 weeks
Change in executive function and attention
Trail Making Test, with scores including time taken to complete and number of errors made.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 Weeks
Change in presence of circulating inflammatory biomarkers (hs-CRP)
Blood samples analysed for presence of inflammatory cytokines
Measured: 12 weeks
Change in circulating biomarkers of neuronal functioning and cognitive decline (BDNF)
Blood samples analysed for presence of circulating biomarkers of neural function
Measured: 12 weeks
Change in circulating biomarkers of lipid metabolism (total-, HDL-, LDL-cholesterol)
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
Measured: 12 weeks
Change in circulating biomarkers of lipid metabolism (triglycerides)
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
Measured: 12 weeks
Secondary outcomes (4)
Changes in energy expenditure and sleep
Actigraphs to be used to measure changes in activity and sleep patterns of participants.
Measured: 12 weeks
Genetics related to neurodegenerative disease
Blood samples to be analysed for genes associated with neurodegenerative disease and dementia (eg. C9ORF72, APOE-4)
Measured: Baseline
Biomarkers of gut permability and endotoxemia (LPS)
Blood serum/plasma samples to be analysed for presence of lipopolysaccharide (LPS) as a biomarker of gut permability and possible endotoxemia
Measured: 12 weeks
Levels of sunlight exposure
Self-reported levels of daily sunlight exposure to be measured using a brief questionnaire
Measured: Baseline, Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2018
- Study start2 Oct 2018
- Primary completion22 May 2020
- Study completion22 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind placebo-controlled parallel intervention
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
- Responsible party
- Sponsor
- Investigators
- David Vauzour, PhD, Principal investigator, University of East AngliaMichael Hornberger, PhD, Principal investigator, University of East Anglia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03679533
- Sponsor's protocol ID
- R204719
- Acronym
- COMBAT
- Status last verified
- Sep 2020
- First submitted
- 15 Jun 2018
- Last updated
- 30 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35662954
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Cranberries on the Microbiome and the Brain in Healthy Ageing: A Feasibility Intervention
- ClinicalTrials.gov ID
- NCT03679533
- Acronym / sponsor ID
- COMBAT / R204719
- Conditions
- Aging, Cognitive Decline
- Keywords
- Cognition, Ageing, Nutrition, Microbiome, Flavonoids
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Collaborators
- Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
- Study start
- 2 Oct 2018 (actual)
- Primary completion
- 22 May 2020 (actual)
- Study completion
- 22 May 2020 (actual)
- First posted
- 20 Sep 2018 (actual)
- 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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind placebo-controlled parallel intervention
| Arm | Type | Receives |
|---|---|---|
| Active Cranberry Study Food | Active comparator | Dietary Supplement: Freeze-Dried Cranberry Powder |
| Placebo Study Food | Placebo comparator | Dietary Supplement: Placebo |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
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 |
|---|---|---|
| Freeze-Dried Cranberry PowderFreeze-dried cranberry powder (or matched placebo), approximating 500mg active flavonoids per day, taken twice daily for 12 weeks. | Dietary supplement | Active Cranberry Study Food |
| PlaceboPlacebo food powder matched for taste, colour, energy and macronutrient content to the active cranberry powder. | Dietary supplement | Placebo Study Food |
Primary outcome
Gut microflora speciation and metabolism
Time frame: 12 weeks
Measured in faecal and serum samples.
Change in volumes of hippocampus and other key brain structures
Time frame: 12 weeks
Structural magnetic resonance imaging
Change in cerebrovascular blood flow
Time frame: 12 weeks
Measured using spectroscopy
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.
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.
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.
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.
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.
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.
Change in presence of circulating inflammatory biomarkers (hs-CRP)
Time frame: 12 weeks
Blood samples analysed for presence of inflammatory cytokines
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
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
Change in circulating biomarkers of lipid metabolism (triglycerides)
Time frame: 12 weeks
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
4 secondary outcomes
Changes in energy expenditure and sleep
Time frame: 12 weeks
Genetics related to neurodegenerative disease
Time frame: Baseline
Biomarkers of gut permability and endotoxemia (LPS)
Time frame: 12 weeks
Levels of sunlight exposure
Time frame: Baseline, Follow-up
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 30 Sep 2020.
- Derived from this study: PubMed 35662954Flanagan 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.
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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.
David Vauzour, PhD principal investigator
University of East Anglia
Michael Hornberger, PhD principal investigator
University of East Anglia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Freeze-Dried Cranberry Powder in people with Aging and Cognitive Decline, run by University of East Anglia at 1 site in United Kingdom.
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 5 inclusion and 19 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 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
Gut microflora speciation and metabolism (time frame: 12 weeks). The study lists 13 primary outcomes in all. 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 NCT03679533, which also lists 1 linked publication.
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 30 Sep 2020.