Back to resultsThe Impact of Cranberries On the Microbiome and the Brain in Healthy Ageing sTudy (COMBAT) (COMBAT)
Primary Purpose
Aging, Cognitive Decline
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Freeze-Dried Cranberry Powder
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Aging focused on measuring Cognition, Ageing, Nutrition, Microbiome, Flavonoids
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.
Sites / Locations
- University of East Anglia
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Active Cranberry Study Food
Placebo Study Food
Arm Description
Outcomes
Primary Outcome Measures
Gut microflora speciation and metabolism
Measured in faecal and serum samples.
Change in volumes of hippocampus and other key brain structures
Structural magnetic resonance imaging
Change in cerebrovascular blood flow
Measured using spectroscopy
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.
Change in spatial navigation abilities
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
Trail Making Test, with scores including time taken to complete and number of errors made.
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.
Change in spatial navigation abilities
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
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)
Blood samples analysed for presence of inflammatory cytokines
Change in circulating biomarkers of neuronal functioning and cognitive decline (BDNF)
Blood samples analysed for presence of circulating biomarkers of neural function
Change in circulating biomarkers of lipid metabolism (total-, HDL-, LDL-cholesterol)
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
Change in circulating biomarkers of lipid metabolism (triglycerides)
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
Secondary Outcome Measures
Changes in energy expenditure and sleep
Actigraphs to be used to measure changes in activity and sleep patterns of participants.
Genetics related to neurodegenerative disease
Blood samples to be analysed for genes associated with neurodegenerative disease and dementia (eg. C9ORF72, APOE-4)
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
Levels of sunlight exposure
Self-reported levels of daily sunlight exposure to be measured using a brief questionnaire
Full Information
NCT ID
NCT03679533
First Posted
June 15, 2018
Last Updated
September 29, 2020
Sponsor
University of East Anglia
Collaborators
Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
1. Study Identification
Unique Protocol Identification Number
NCT03679533
Brief Title
The Impact of Cranberries On the Microbiome and the Brain in Healthy Ageing sTudy (COMBAT)
Acronym
COMBAT
Official Title
The Impact of Cranberries on the Microbiome and the Brain in Healthy Ageing: A Feasibility Intervention
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
October 2, 2018 (Actual)
Primary Completion Date
May 22, 2020 (Actual)
Study Completion Date
May 22, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of East Anglia
Collaborators
Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aging, Cognitive Decline
Keywords
Cognition, Ageing, Nutrition, Microbiome, Flavonoids
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Double-blind placebo-controlled parallel intervention
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active Cranberry Study Food
Arm Type
Active Comparator
Arm Title
Placebo Study Food
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Freeze-Dried Cranberry Powder
Intervention Description
Freeze-dried cranberry powder (or matched placebo), approximating 500mg active flavonoids per day, taken twice daily for 12 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo food powder matched for taste, colour, energy and macronutrient content to the active cranberry powder.
Primary Outcome Measure Information:
Title
Gut microflora speciation and metabolism
Description
Measured in faecal and serum samples.
Time Frame
12 weeks
Title
Change in volumes of hippocampus and other key brain structures
Description
Structural magnetic resonance imaging
Time Frame
12 weeks
Title
Change in cerebrovascular blood flow
Description
Measured using spectroscopy
Time Frame
12 weeks
Title
Change in global cognition
Description
Global cognition to be measured using the Addenbrooke's Cognitive Examination - III, from 0-100, with higher scores indicating better global cognitive performance.
Time Frame
12 weeks
Title
Change in spatial navigation abilities
Description
The Supermarket Test, with outcomes including accurate reporting of starting direction, and accurate indication of end position and direction.
Time Frame
12 weeks
Title
Change in executive function and attention
Description
Trail Making Test, with scores including time taken to complete and number of errors made.
Time Frame
12 weeks
Title
Change in memory performance
Description
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.
Time Frame
12 weeks
Title
Change in spatial navigation abilities
Description
SeaHero Quest Test, with outcomes including time taken to complete, accuracy of path taken and number of errors made.
Time Frame
12 weeks
Title
Change in executive function and attention
Description
Digit Span Backwards, scored out of a possible 14 for numbers recited backwards in the correct order.
Time Frame
12 Weeks
Title
Change in presence of circulating inflammatory biomarkers (hs-CRP)
Description
Blood samples analysed for presence of inflammatory cytokines
Time Frame
12 weeks
Title
Change in circulating biomarkers of neuronal functioning and cognitive decline (BDNF)
Description
Blood samples analysed for presence of circulating biomarkers of neural function
Time Frame
12 weeks
Title
Change in circulating biomarkers of lipid metabolism (total-, HDL-, LDL-cholesterol)
Description
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
Time Frame
12 weeks
Title
Change in circulating biomarkers of lipid metabolism (triglycerides)
Description
Blood samples analysed for presence of circulating biomarkers of lipid metabolism
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Changes in energy expenditure and sleep
Description
Actigraphs to be used to measure changes in activity and sleep patterns of participants.
Time Frame
12 weeks
Title
Genetics related to neurodegenerative disease
Description
Blood samples to be analysed for genes associated with neurodegenerative disease and dementia (eg. C9ORF72, APOE-4)
Time Frame
Baseline
Title
Biomarkers of gut permability and endotoxemia (LPS)
Description
Blood serum/plasma samples to be analysed for presence of lipopolysaccharide (LPS) as a biomarker of gut permability and possible endotoxemia
Time Frame
12 weeks
Title
Levels of sunlight exposure
Description
Self-reported levels of daily sunlight exposure to be measured using a brief questionnaire
Time Frame
Baseline, Follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Vauzour, PhD
Organizational Affiliation
University of East Anglia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Hornberger, PhD
Organizational Affiliation
University of East Anglia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of East Anglia
City
Norwich
State/Province
Norfolk
ZIP/Postal Code
NR4 7UQ
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
35662954
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.
Results Reference
derived
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The Impact of Cranberries On the Microbiome and the Brain in Healthy Ageing sTudy (COMBAT)
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