Blood PressureNO3NCT03871777
Dietary Nitrate Intake in Vegetarians and Omnivores
A study testing Chlorhexidine mouthwash in people with Blood Pressure, run by University of Plymouth at 1 site in United Kingdom.
Trial summary
Vegetarian diets are commonly associated with lower blood pressure levels. This has been related to greater consumption of inorganic nitrate, since vegetables are the main source of this anion. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Blood Pressure
- What is being tested?
- Chlorhexidine mouthwash
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 May 2016to 12 Nov 2018
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy vegetarians (vegans and ovo-lacto vegetarians) following this dietary pattern for at least a year.
- Health omnivores
Who cannot join
- Smokers
- Individuals taking any medications or recreational drugs.
- Individuals with pre-existing medical conditions such as hypertension, diabetes, dyslipidaemia or dental conditions (gingivitis).
- Individuals using mouthwash or tongue scrapes were excluded from this study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Laboratory of Nutrition, Exercise & Health
Plymouth, Devon, PL4 8AA
About this study
Official title: Dietary Intake of Inorganic Nitrate in Vegetarians and Omnivores and Its Impact on Blood Pressure, Resting Metabolic Rate and the Oral Microbiome
Vegetarian diets are commonly associated with lower blood pressure levels. This has been related to greater consumption of inorganic nitrate, since vegetables are the main source of this anion. Dietary nitrate is reduced to nitrite by commensal bacteria in the mouth, which in turn leads to increased circulatory nitrite availability. Nitrite can form nitric oxide by several pathways promoting a reduction in the vascular tone and lower blood pressure.
- Conditions
- Blood Pressure
- Being tested
- Placebo mouthwash, Chlorhexidine mouthwash
- Keywords
- nitrate, vegetarian, nitrite, oral microbiome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo mouthwashOther
Participants received placebo mouthwash (ultrapure unflavoured water) with which they rinsed their mouth for one minute, twice a day for 7 days. Resting metabolic rate and blood pressure were measured on day eight. Additionally, blood and saliva samples were taken from all the participants. Dietary records of seven days were also collected in order to confirm the foods and portion sizes consumed, preparation methods, recipes and any brand names.
Chlorhexidine mouthwashOther
After using placebo and complete all the physiological measurements, participants were given a further one-week supply of antibacterial mouthwash containing 0.2% chlorhexidine (Corsodyl, GlaxoSmithKline, UK), encouraged to rinse their mouth for one minute, twice a day for 7 more days. They returned to the laboratory in 7 days to repeat all measurements in the same order.
| Study group | Role | What they receive |
|---|---|---|
| Vegetarians | Active comparator | Healthy vegetarians (vegans and lacto-ovo vegetarians) 18 and 50 years formed this arm. Receives: Other: Placebo mouthwash; Other: Chlorhexidine mouthwash |
| Omnivores | Sham comparator | Healthy omnivores with similar characteristics of vegetarians (age, body mass index, gender and physical activity levels) formed this arm Receives: Other: Placebo mouthwash; Other: Chlorhexidine mouthwash |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dietary nitrate intake
Macro- and micronutrient intake of seven-day food diaries were analysed using a nutritional analysis software programme (Microdiet, Downlee Systems, Chapel-en-le-Frith, UK). Nitrate content of vegetables was mainly obtained from the European Food Safety Authority and additional data for spinach and lettuce from the Food Standards Agency. Nitrate and total polyphenol figures were uploaded to the Microdiet database prior to analysis.
Measured: 7 days
Concentration of nitrate and nitrite in plasma and saliva
Whole blood was collected into lithium-heparin tubes (BD Vacutainer®, Becton Dickinson, Plymouth, UK) and rapidly centrifuged at 4,000 rpm and 4°C for 10 minutes. The plasma was then separated, frozen at -80°C until further analyses of nitrate and nitrite were performed. Non-stimulated saliva (3 milliliters) was also collected into a sterile falcon tube and rapidly frozen at -80°C. Then, nitrate and nitrite were measured in plasma and saliva using ozone-based chemiluminescence.
Measured: 7 days
Change in blood pressure
Systolic, diastolic and mean arterial blood pressure was measured following British Hypertension Guidelines. Three successive supine readings were taken using an oscillometric device (Connex ProBP 3400 Digital Blood Pressure Device, Welch Allyn UK Ltd.) with a one minute rest between readings. The second and third readings were averaged to determine mean clinic blood pressure.
Measured: 7 days
Change in oral nitrate-reducing capacity
Nitrate-reducing capacity of oral bacteria was analysed to compare vegetarians and omnivores and treatments (placebo mouthwash vs antibacterial mouthwash). Participants were instructed to hold 10 milliliters of water containing sodium nitrate (80 μicromols) in their mouth for 5 minutes. The mouth rinse was collected into a Falcon sterile tube and centrifuged (4,500 rpm, 4°C) for 10 minutes. The supernatant was collected and stored at -80°C before measuring absolute nitrite concentration.
Measured: 7 days
Change in Resting Energy Expenditure
Resting Energy Expenditure was analysed using indirect calorimetry after using the placebo mouthwash and antibacterial mouthwash
Measured: 7 days
Change oral microbiome
bundance of oral bacteria was analysed using 16S ribosomal ribonucleic acid (rRNA) after using the placebo mouthwash and antibacterial mouthwash.
Salivary DNA was extracted using a DNA kit (QIAamp® DNeasy Blood \& Tissue Kit). Polymerase chain reaction (PCR) amplification of the 16S rRNA V1-2 region was carried out using universal 16S primers 27 F (5'-AGA GTT TGA TCM TGG CTC AG-3') and 338 R (5'-GCW GCC WCC CGT AGG WGT-3'). Single band PCR products were purified and quantified with Qubit 2.0 Fluorometer (Invitrogen, CA, USA). Sequencing was performed on an Ion Torrent Personal Genome Machine.
Measured: 7 days
Change in blood biomarkers
Blood markers were analyzed to assess differences between vegetarians and omnivores to control for diabetes and dyslipidaemia and to analyse the effect of antibacterial mouthwash.
Whole blood glucose and lactate was measured using a biochemistry analyser (YSI 2300 Stat Plus, YSI Life Sciences, USA). Total cholesterol, triglycerides, high density lipoproteins (HDL) and low density lipoproteins (LDL) were analysed with enzymatic methods using the Roche 702 spectrophotometric module of a Cobas 8000 analyser (Roche Diagnostics Ltd, UK)
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2019
- Study start9 May 2016
- Primary completion4 Sep 2017
- Study completion12 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Blood PressureStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Plymouth
- Sponsor type
- University, hospital or other
- Collaborators
- University of the West of Scotland
- Responsible party
- Principal investigator, Raul Bescos, University of Plymouth
- Investigators
- Raul Bescos, PhD, Study director, University of Plymouth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03871777
- Sponsor's protocol ID
- 15/16-469
- Acronym
- NO3
- Status last verified
- Oct 2019
- First submitted
- 9 Mar 2019
- Last updated
- 10 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be shared as requested
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Intake of Inorganic Nitrate in Vegetarians and Omnivores and Its Impact on Blood Pressure, Resting Metabolic Rate and the Oral Microbiome
- ClinicalTrials.gov ID
- NCT03871777
- Acronym / sponsor ID
- NO3 / 15/16-469
- Conditions
- Blood Pressure
- Keywords
- nitrate, vegetarian, nitrite, oral microbiome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of PlymouthUniversity, hospital or other
- Collaborators
- University of the West of Scotland
- Study start
- 9 May 2016 (actual)
- Primary completion
- 4 Sep 2017 (actual)
- Study completion
- 12 Nov 2018 (actual)
- First posted
- 12 Mar 2019 (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.
Vegetarian diets are commonly associated with lower blood pressure levels. This has been related to greater consumption of inorganic nitrate, since vegetables are the main source of this anion. Dietary nitrate is reduced to nitrite by commensal bacteria in the mouth, which in turn leads to increased circulatory nitrite availability. Nitrite can form nitric oxide by several pathways promoting a reduction in the vascular tone and lower blood pressure.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vegetarians | Active comparator | Other: Placebo mouthwash, Other: Chlorhexidine mouthwashHealthy vegetarians (vegans and lacto-ovo vegetarians) 18 and 50 years formed this arm. |
| Omnivores | Sham comparator | Other: Placebo mouthwash, Other: Chlorhexidine mouthwashHealthy omnivores with similar characteristics of vegetarians (age, body mass index, gender and physical activity levels) formed this arm |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy vegetarians (vegans and ovo-lacto vegetarians) following this dietary pattern for at least a year.
- Health omnivores
Key exclusion criteria (4 listed)
- Smokers
- Individuals taking any medications or recreational drugs.
- Individuals with pre-existing medical conditions such as hypertension, diabetes, dyslipidaemia or dental conditions (gingivitis).
- Individuals using mouthwash or tongue scrapes were excluded from this study
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 |
|---|---|---|
| Placebo mouthwashParticipants received placebo mouthwash (ultrapure unflavoured water) with which they rinsed their mouth for one minute, twice a day for 7 days. Resting metabolic rate and blood pressure were measured on day eight. Additionally, blood and saliva samples were taken from all the participants. Dietary records of seven days were also collected in order to confirm the foods and portion sizes consumed, preparation methods, recipes and any brand names. | Other | Omnivores, Vegetarians |
| Chlorhexidine mouthwashAfter using placebo and complete all the physiological measurements, participants were given a further one-week supply of antibacterial mouthwash containing 0.2% chlorhexidine (Corsodyl, GlaxoSmithKline, UK), encouraged to rinse their mouth for one minute, twice a day for 7 more days. They returned to the laboratory in 7 days to repeat all measurements in the same order. | Other | Omnivores, Vegetarians |
Primary outcome
Dietary nitrate intake
Time frame: 7 days
Macro- and micronutrient intake of seven-day food diaries were analysed using a nutritional analysis software programme (Microdiet, Downlee Systems, Chapel-en-le-Frith, UK). Nitrate content of vegetables was mainly obtained from the European Food Safety Authority and additional data for spinach and lettuce from the Food Standards Agency. Nitrate and total polyphenol figures were uploaded to the Microdiet database prior to analysis.
Concentration of nitrate and nitrite in plasma and saliva
Time frame: 7 days
Whole blood was collected into lithium-heparin tubes (BD Vacutainer®, Becton Dickinson, Plymouth, UK) and rapidly centrifuged at 4,000 rpm and 4°C for 10 minutes. The plasma was then separated, frozen at -80°C until further analyses of nitrate and nitrite were performed. Non-stimulated saliva (3 milliliters) was also collected into a sterile falcon tube and rapidly frozen at -80°C. Then, nitrate and nitrite were measured in plasma and saliva using ozone-based chemiluminescence.
Change in blood pressure
Time frame: 7 days
Systolic, diastolic and mean arterial blood pressure was measured following British Hypertension Guidelines. Three successive supine readings were taken using an oscillometric device (Connex ProBP 3400 Digital Blood Pressure Device, Welch Allyn UK Ltd.) with a one minute rest between readings. The second and third readings were averaged to determine mean clinic blood pressure.
Change in oral nitrate-reducing capacity
Time frame: 7 days
Nitrate-reducing capacity of oral bacteria was analysed to compare vegetarians and omnivores and treatments (placebo mouthwash vs antibacterial mouthwash). Participants were instructed to hold 10 milliliters of water containing sodium nitrate (80 μicromols) in their mouth for 5 minutes. The mouth rinse was collected into a Falcon sterile tube and centrifuged (4,500 rpm, 4°C) for 10 minutes. The supernatant was collected and stored at -80°C before measuring absolute nitrite concentration.
Change in Resting Energy Expenditure
Time frame: 7 days
Resting Energy Expenditure was analysed using indirect calorimetry after using the placebo mouthwash and antibacterial mouthwash
Change oral microbiome
Time frame: 7 days
bundance of oral bacteria was analysed using 16S ribosomal ribonucleic acid (rRNA) after using the placebo mouthwash and antibacterial mouthwash. Salivary DNA was extracted using a DNA kit (QIAamp® DNeasy Blood \& Tissue Kit). Polymerase chain reaction (PCR) amplification of the 16S rRNA V1-2 region was carried out using universal 16S primers 27 F (5'-AGA GTT TGA TCM TGG CTC AG-3') and 338 R (5'-GCW GCC WCC CGT AGG WGT-3'). Single band PCR products were purified and quantified with Qubit 2.0 Fluorometer (Invitrogen, CA, USA). Sequencing was performed on an Ion Torrent Personal Genome Machine.
Change in blood biomarkers
Time frame: 7 days
Blood markers were analyzed to assess differences between vegetarians and omnivores to control for diabetes and dyslipidaemia and to analyse the effect of antibacterial mouthwash. Whole blood glucose and lactate was measured using a biochemistry analyser (YSI 2300 Stat Plus, YSI Life Sciences, USA). Total cholesterol, triglycerides, high density lipoproteins (HDL) and low density lipoproteins (LDL) were analysed with enzymatic methods using the Roche 702 spectrophotometric module of a Cobas 8000 analyser (Roche Diagnostics Ltd, UK)
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 10 Oct 2019.
- Individual participant dataSharing planned: No. Data will be shared as requested
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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.
Raul Bescos, PhD study director
University of Plymouth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chlorhexidine mouthwash in people with Blood Pressure, run by University of Plymouth 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 2 inclusion and 4 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 10 Oct 2019. 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?
Dietary nitrate intake (time frame: 7 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Oct 2019.