Dietary SupplementationsCOGNITNCT05518214
'Oral Microbiome -Dietary Nitrate' Interactions and Cognitive Health in Older Age
A study testing Beetroot in people with Dietary Supplementations, run by University of Exeter at 1 site in United Kingdom.
Trial summary
Vegetable rich diets contain natural inorganic nitrate. These diets are linked to good heart and brain health. Human cells cannot 'activate' nitrate. Humans must rely on specific bacteria living in the mouth to digest nitrate to an active form called 'nitric oxide' that we can use in the body. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dietary Supplementations
- What is being tested?
- Beetroot
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Sep 2021to 31 Oct 2022
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent.
- Male or Female.
- Over 50 years of age.
- Access to a postal service (Royal Mail)
- Access to the Internet.
- Mainland UK resident.
- APOE genotype available in PROTECT database.
Who cannot join
- Diagnosis of dementia, because the participant may be unable to provide informed consent.
- Current or previous smoker (within the last year).
- Regular drinkers of alcoholic beverages which are over 14% ABV undiluted.
- Current or recent use of antibiotics (within the past 3 months).
- Self-reported substantial use of mouthwash or tongue scrapers within the past month.
- Self-reported periodontitis, gingivitis or other oral disease.
- No available APOE genotyping in PROTECT database.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Exeter Sport and Health Sciences
Exeter, Devon, EX12LU
About this study
Vegetable rich diets contain natural inorganic nitrate. These diets are linked to good heart and brain health. Human cells cannot 'activate' nitrate. Humans must rely on specific bacteria living in the mouth to digest nitrate to an active form called 'nitric oxide' that we can use in the body. We have found that nitrate makes the oral microbiome healthier and improves nitric oxide production. This study will investigate whether changes in oral bacteria caused by dietary nitrate are linked to any changes in brain performance.We will ask 60 healthy men and women of over 50 years of age to take part. We will ask them to drink either nitrate-rich beetroot juice or placebo juice daily for 12 weeks. We will do this investigation entirely remotely by using online tools and by posting of supplements and samples. We will sample the volunteers' oral microbiome and assess their cognitive performance before and after dietary supplementation. We will analyse the nitric oxide content in the samples that the volunteers post us. We will try to findgroups of bacteria linked with goodbrainfunction.The results will help us better understand how oral bacteria may influence cognitive function in older age.
Read the detailed description
Oral dysbiosis and poor dental health have been associated with impaired cardiovascular and cognitive health, but it is not known which characteristics of bacterial communities specifically might mediate such relationships. One mechanism by which the oral microbiota may influence health is its contribution to production of the signalling molecule, nitric oxide (NO), which, among many other functions, regulates vascular tone and neurotransmission . The capacity for endogenous NO production via the enzymatic NOS synthase pathway declines in older age, contributing to development of arterial hypertension, reduced physical and cognitive functional capacity, and increased morbidity. Therefore, the composition of the oral microbiota may be particularly important to enable older people to benefit from a nitrate-rich diets, such as the Mediterranean diet, which has been associated with reduced risk of developing dementia in older age. A key genetic risk factor for dementia is a form of apolipoprotein E gene called APOE4, which may also modulate responsiveness to dietary interventions.The purpose of this research is to investigate whether specific groups of oral bacteria, that are sensitive to change with dietary nitrate supplementation, are correlated with indices of cognitive function (primary objective) as well as APOE genotype, diet, physical activity, and markers of vascular health (secondary objectives), in people over 50 years of age.
- Conditions
- Dietary Supplementations
- Being tested
- Beetroot, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BeetrootDietary supplement
Participants receive a 12-week supply of beetroot juice.
PlaceboDietary supplement
Participants receive a 12-week supply of placebo beetroot juice.
| Study group | Role | What they receive |
|---|---|---|
| Beetroot | Experimental | Participants will receive nitrate-rich (70 ml, containing 6.4 mmol of nitrate) beetroot juice, by Beet It, James White. Participants will take 1 beetroot juice drink everyday for 12 weeks. Receives: Dietary Supplement: Beetroot |
| Placebo | Placebo comparator | Participants will receive a placebo beetroot juice with the nitrate removed, by Beet It, James White. Participants will take 1 placebo juice drink everyday for 12 weeks. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline oral bacteria co-occurrence at 12 weeks using oral microbiome abundance data and WGCNA analysis.
Identify co-occurring clusters of oral bacteria which are consistently related to indices of cognitive status across dietary interventions with nitrate and placebo. Using oral microbiome abundance data from sequenced oral microbiome DNA in the mouth rinse samples, the change from baseline to post-12 week intervention is measured. WGCNA analysis is used to cluster co-occurring bacteria and detect patterns of grouping.
Measured: Change measured between baseline and 12-weeks post-intervention.
Secondary outcomes (4)
Change from baseline oral nitric oxide bioavailability at 12 weeks using ozone-based chemiluminescence.
The change from baseline to post-12 week intervention nitrate and nitrite concentrations in mouth rinse samples is measured using ozone-based chemiluminescence.
Measured: Change measured between baseline and 12-weeks post-intervention.
Change from baseline composition of the oral microbiome at 12 weeks using oral microbiome abundance data from sequencing oral microbiome DNA in mouth rinse samples.
Oral microbiome sequencing of bacterial DNA isolated from mouth rinse samples. The change in the composition of the oral microbiome is measured from baseline to post-12 week intervention using oral microbiome abundance data.
Measured: Change measured between baseline and 12-weeks post-intervention.
Change from baseline cognitive status at 12 weeks.
'Factors of Longitudinal Attention, Memory and Executive Function' (FLAME) composite score. Online FLAME cognitive assessment battery completed at home by the participants via the online PROTECT study. The FLAME cognitive assessment is a validated battery of online cognitive tests where correct/incorrect responses and response time are measured.
Measured: Change measured between baseline and 12-weeks post-intervention.
Correlation between oral microbiome and existing descriptive data.
Correlation of oral microbiome with existing PROTECT cohort variables (APOE genotype, diet, physical activity). The oral microbiome abundance data is correlated with APOE genotype and dietary and physical questionnaire data.
Measured: Correlation measured after 12-weeks post-intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2022
- Study start29 Sep 2021
- Primary completion31 Oct 2022
- Study completion31 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Dietary SupplementationsStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05518214
- Sponsor's protocol ID
- COGNIT
- Acronym
- COGNIT
- Status last verified
- Jan 2024
- First submitted
- 25 Jul 2022
- Last updated
- 11 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Briskey D, Tucker PS, Johnson DW, Coombes JS. Microbiota and the nitrogen cycle: Implications in the development and progression of CVD and CKD. Nitric Oxide. 2016 Jul 1;57:64-70. doi: 10.1016/j.niox.2016.05.002. Epub 2016 May 7.
PubMed 27164294Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001 Jan;81(1):209-237. doi: 10.1152/physrev.2001.81.1.209.
PubMed 11152758Bryan NS, Tribble G, Angelov N. Oral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure. Curr Hypertens Rep. 2017 Apr;19(4):33. doi: 10.1007/s11906-017-0725-2.
PubMed 28353075Vanhatalo A, L'Heureux JE, Kelly J, Blackwell JR, Wylie LJ, Fulford J, Winyard PG, Williams DW, van der Giezen M, Jones AM. Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions. Redox Biol. 2021 May;41:101933. doi: 10.1016/j.redox.2021.101933. Epub 2021 Mar 5.
PubMed 33721836Brooker H, Williams G, Hampshire A, Corbett A, Aarsland D, Cummings J, Molinuevo JL, Atri A, Ismail Z, Creese B, Fladby T, Thim-Hansen C, Wesnes K, Ballard C. FLAME: A computerized neuropsychological composite for trials in early dementia. Alzheimers Dement (Amst). 2020 Oct 14;12(1):e12098. doi: 10.1002/dad2.12098. eCollection 2020.
PubMed 33088895
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 'Oral Microbiome -Dietary Nitrate' Interactions and Cognitive Health in Older Age
- ClinicalTrials.gov ID
- NCT05518214
- Acronym / sponsor ID
- COGNIT / COGNIT
- Conditions
- Dietary Supplementations
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Study start
- 29 Sep 2021 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 26 Aug 2022 (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.
Vegetable rich diets contain natural inorganic nitrate. These diets are linked to good heart and brain health. Human cells cannot 'activate' nitrate. Humans must rely on specific bacteria living in the mouth to digest nitrate to an active form called 'nitric oxide' that we can use in the body. We have found that nitrate makes the oral microbiome healthier and improves nitric oxide production. This study will investigate whether changes in oral bacteria caused by dietary nitrate are linked to any changes in brain performance.We will ask 60 healthy men and women of over 50 years of age to take part. We will ask them to drink either nitrate-rich beetroot juice or placebo juice daily for 12 weeks. We will do this investigation entirely remotely by using online tools and by posting of supplements and samples. We will sample the volunteers' oral microbiome and assess their cognitive performance before and after dietary supplementation. We will analyse the nitric oxide content in the samples that the volunteers post us. We will try to findgroups of bacteria linked with goodbrainfunction.The results will help us better understand how oral bacteria may influence cognitive function in older age.
Detailed description
Oral dysbiosis and poor dental health have been associated with impaired cardiovascular and cognitive health, but it is not known which characteristics of bacterial communities specifically might mediate such relationships. One mechanism by which the oral microbiota may influence health is its contribution to production of the signalling molecule, nitric oxide (NO), which, among many other functions, regulates vascular tone and neurotransmission . The capacity for endogenous NO production via the enzymatic NOS synthase pathway declines in older age, contributing to development of arterial hypertension, reduced physical and cognitive functional capacity, and increased morbidity. Therefore, the composition of the oral microbiota may be particularly important to enable older people to benefit from a nitrate-rich diets, such as the Mediterranean diet, which has been associated with reduced risk of developing dementia in older age. A key genetic risk factor for dementia is a form of apolipoprotein E gene called APOE4, which may also modulate responsiveness to dietary interventions.The purpose of this research is to investigate whether specific groups of oral bacteria, that are sensitive to change with dietary nitrate supplementation, are correlated with indices of cognitive function (primary objective) as well as APOE genotype, diet, physical activity, and markers of vascular health (secondary objectives), in people over 50 years of age.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beetroot | Experimental | Dietary Supplement: BeetrootParticipants will receive nitrate-rich (70 ml, containing 6.4 mmol of nitrate) beetroot juice, by Beet It, James White. Participants will take 1 beetroot juice drink everyday for 12 weeks. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboParticipants will receive a placebo beetroot juice with the nitrate removed, by Beet It, James White. Participants will take 1 placebo juice drink everyday for 12 weeks. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participant is willing and able to give informed consent.
- Male or Female.
- Over 50 years of age.
- Access to a postal service (Royal Mail)
- Access to the Internet.
Key exclusion criteria (7 listed)
- Diagnosis of dementia, because the participant may be unable to provide informed consent.
- Current or previous smoker (within the last year).
- Regular drinkers of alcoholic beverages which are over 14% ABV undiluted.
- Current or recent use of antibiotics (within the past 3 months).
- Self-reported substantial use of mouthwash or tongue scrapers within the past month.
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 |
|---|---|---|
| BeetrootParticipants receive a 12-week supply of beetroot juice. | Dietary supplement | Beetroot |
| PlaceboParticipants receive a 12-week supply of placebo beetroot juice. | Dietary supplement | Placebo |
Primary outcome
Change from baseline oral bacteria co-occurrence at 12 weeks using oral microbiome abundance data and WGCNA analysis.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Identify co-occurring clusters of oral bacteria which are consistently related to indices of cognitive status across dietary interventions with nitrate and placebo. Using oral microbiome abundance data from sequenced oral microbiome DNA in the mouth rinse samples, the change from baseline to post-12 week intervention is measured. WGCNA analysis is used to cluster co-occurring bacteria and detect patterns of grouping.
4 secondary outcomes
Change from baseline oral nitric oxide bioavailability at 12 weeks using ozone-based chemiluminescence.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Change from baseline composition of the oral microbiome at 12 weeks using oral microbiome abundance data from sequencing oral microbiome DNA in mouth rinse samples.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Change from baseline cognitive status at 12 weeks.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Correlation between oral microbiome and existing descriptive data.
Time frame: Correlation measured after 12-weeks post-intervention.
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 11 Jan 2024.
- Background: PubMed 27164294Briskey D, Tucker PS, Johnson DW, Coombes JS. Microbiota and the nitrogen cycle: Implications in the development and progression of CVD and CKD. Nitric Oxide. 2016 Jul 1;57:64-70. doi: 10.1016/j.niox.2016.05.002. Epub 2016 May 7.
- Background: PubMed 11152758Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001 Jan;81(1):209-237. doi: 10.1152/physrev.2001.81.1.209.
- Background: PubMed 28353075Bryan NS, Tribble G, Angelov N. Oral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure. Curr Hypertens Rep. 2017 Apr;19(4):33. doi: 10.1007/s11906-017-0725-2.
- Background: PubMed 33721836Vanhatalo A, L'Heureux JE, Kelly J, Blackwell JR, Wylie LJ, Fulford J, Winyard PG, Williams DW, van der Giezen M, Jones AM. Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions. Redox Biol. 2021 May;41:101933. doi: 10.1016/j.redox.2021.101933. Epub 2021 Mar 5.
- Background: PubMed 33088895Brooker H, Williams G, Hampshire A, Corbett A, Aarsland D, Cummings J, Molinuevo JL, Atri A, Ismail Z, Creese B, Fladby T, Thim-Hansen C, Wesnes K, Ballard C. FLAME: A computerized neuropsychological composite for trials in early dementia. Alzheimers Dement (Amst). 2020 Oct 14;12(1):e12098. doi: 10.1002/dad2.12098. eCollection 2020.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Beetroot in people with Dietary Supplementations, run by University of Exeter 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 7 inclusion and 7 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 11 Jan 2024. 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?
Change from baseline oral bacteria co-occurrence at 12 weeks using oral microbiome abundance data and WGCNA analysis. (time frame: Change measured between baseline and 12-weeks post-intervention.). 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 NCT05518214, which also lists 5 linked publications.
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 11 Jan 2024.