'Oral Microbiome -Dietary Nitrate' Interactions and Cognitive Health in Older Age

NCT05518214 | Completed DMC

• 1 other identifier: COGNIT
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Dietary Supplementations

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  Change measured between baseline and 12-weeks post-intervention.

• Change from baseline cognitive status at 12 weeks.

  Change measured between baseline and 12-weeks post-intervention.

• Correlation between oral microbiome and existing descriptive data.

  Correlation measured after 12-weeks post-intervention.

Study Arms (2)

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.

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.

Dietary Supplement: Placebo

Interventions

Beetroot DIETARY_SUPPLEMENT

Participants receive a 12-week supply of beetroot juice.

Beetroot

Placebo DIETARY_SUPPLEMENT

Participants receive a 12-week supply of placebo beetroot juice.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

University of Exeter Sport and Health Sciences

Exeter, Devon, EX12LU, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 27164294 BACKGROUND

• Stamler 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.

  PMID: 11152758 BACKGROUND

• Bryan 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.

  PMID: 28353075 BACKGROUND

• Vanhatalo 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.

  PMID: 33721836 BACKGROUND

• Brooker 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.

  PMID: 33088895 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind study where both the Participant and Investigator are blind to the supplement given.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: August 26, 2022
• Study Start: September 29, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)