No Dental DiseaseREBOC2NCT03784742
Effects of Daily Nitrate Consumption on Oral Bacteria Composition, Blood Pressure and Vascular Function
A study testing Nitrate rich beetroot juice in people with No Dental Disease and Non-smoking, run by University of Reading at 1 site in United Kingdom.
Trial summary
Diseases of the heart and blood vessels, including raised blood pressure, are one of the leading causes of death worldwide. Higher intakes of dietary nitrate, found abundantly in root vegetables such as beetroot, have been shown to have health benefits including lowering blood pressure and improving the elasticity of… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- No Dental Disease, Non-smoking
- What is being tested?
- Nitrate rich beetroot juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Dec 2018to 1 Dec 2021
- 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 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female;
- A signed consent form;
- Blood pressure <140/90 mm Hg;
- BMI range 18.5 - 39.9 kg/m2;
- Age 18-64 years;
- Non-smoking;
- Not taking blood pressure lowering medication or using medications known to influence vascular function such as a glyceryl trinitrate (GTN) spray;
- No recent (within 3 months) or current use of antibiotics.
Who cannot join
- Diagnosed with a chronic illness;
- Anaemia defined as a haemoglobin < 115 g/l for women and <130 g/l for men;
- Individuals with food allergies or allergies to medicated mouthwash or ingredients in the oral products;
- Requirements to take long-term medication active on the oral cavity including prebiotics and probiotics or have taken antibiotics within the last 3 months;
- Gingivitis diagnosis, or periodontal disease or chronic oral complaints or existing oral pathology.
- Less than four natural (enamel) buccal surfaces of upper molars available;
Show all 12Show fewer
- Presence of fixed or removable oral appliances (e.g., dentures, orthodontic wires); xerostomia (a persistent dry mouth) diagnosis;
- Current smoker;
- Already participating in a dietary intervention study or clinical trial;
- Excessive alcohol consumption (> 14 units/wk);
- Females who are pregnant or lactating;
- Individuals not willing to give up using mouthwash or change their dental hygiene routine. Regular consumption or use of xylitol-based products such as toothpaste and chewing gum.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading
Reading, Berkshire, RG6 6AP
About this study
Official title: Investigation of the Effects of Daily Nitrate Consumption on Oral Bacteria Composition, Blood Pressure and Vascular Functio
Diseases of the heart and blood vessels, including raised blood pressure, are one of the leading causes of death worldwide. Higher intakes of dietary nitrate, found abundantly in root vegetables such as beetroot, have been shown to have health benefits including lowering blood pressure and improving the elasticity of blood vessels. Bacteria which reside in the mouth and those in the gastrointestinal tract play an important role in converting dietary nitrate to nitrite and nitric oxide (a chemical which promotes the relaxation of blood vessels). In particular, removal of oral bacteria by using antiseptic mouthwash is accompanied by an increase in blood pressure in subjects with normal blood pressure, even after consuming nitrate-rich foods. To date, very little is known about the role of these oral bacteria in the control of blood pressure, and if there are any differences in bacterial composition between individuals.
Read the detailed description
Interested volunteers will be provided with an outline of the study and asked to complete a medical and lifestyle questionnaire (in person, by email or over the phone). Potentially suitable participants will be identified and asked to attend a screening session after a 12 h overnight fast (not eating during this time and only drinking water) during which the study will be explained in more detail before a consent form is signed. Anthropometric measurements will then be taken including weight, height and blood pressure. A 9 ml blood sample will also be collected on site at the Department of Food and Nutritional Sciences (Hugh Sinclair Unit of Human Nutrition). Subjects who meet the initial inclusion criteria will be invited to a further screening session during which time a dentist will check for dental diseases (e.g. current dental cavities or periodontal infection) and saliva flow rate. Volunteers without periodontal disease and with normal saliva flow will then be invited to participate in the study.
Eligible subjects will then be randomised to one of two treatments: i) up to 70 ml (the amount given will be equivalent to 3.7 mg/kg body weight) beetroot juice (James White Drinks Limited, UK) or ii) a matched volume of placebo beetroot juice (control, James White Drinks Limited, UK) to be consumed daily for 8 weeks. As drinking water is a major source of dietary nitrate, subjects will be provided with a water filter to reduce the nitrate level in their tap water for drinking and cooking during the study period. There will be a wash out period of 4 weeks between the intervention juices. In total, volunteers will be involved in the study for 20 weeks (five months).
On the day before each baseline study visit (weeks 0 and 12), volunteers will be required to fast overnight after having a low nitrate evening meal and only drinking low nitrate mineral water (Buxton mineral water), which will be provided to them, during this time. They will refrain from strenuous exercise and alcohol. On the morning of the study visit, the volunteers will be asked not to brush their teeth before they come to the clinical unit for their study visit.
When they arrive in the fasted state, the participants will be asked to provide a spot urine sample and a stool sample. Body weight and composition will be measured using the Tanita weighing scale, saliva sample and an oral bacteria sample will be collected by swabbing the tongue with a cotton swab. Volunteers will be asked to lie down for 20 minutes prior to the measurement of blood pressure and pulse wave analysis (PWA) using the Mobil-O-Graph device followed by the assessment of microvascular reactivity using Laser Doppler Imaging with iontophoresis. A blood sample of 20 ml (equivalent to just over 1 tablespoon) will then be taken before a light breakfast is provided. Volunteers will then be given a toothbrush and toothpaste to brush their teeth and asked to complete an online food frequency questionnaire (EatwellUK).
During the four-week wash-out period between interventions, participants will be instructed to avoid any beetroot juice drinks and maintain their usual dietary and lifestyle habits.
- Conditions
- No Dental Disease, Non-smoking
- Being tested
- Nitrate rich beetroot juice, Placebo beetroot juice
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrate rich beetroot juiceOther
James White Drinks Limited beetroot juice (0.4-0.45 g nitrate/70 ml drink).
Placebo beetroot juiceOther
James White Drinks Limited Placebo beetroot juice (0 nitrate/70 ml drink).
| Study group | Role | What they receive |
|---|---|---|
| Nitrate-rich Beetroot juice | Active comparator | Nitrate-rich beetroot juice equivalent to 3.7 mg nitrate per kg body weight daily for 8 weeks. Receives: Other: Nitrate rich beetroot juice |
| Placebo beetroot juice | Placebo comparator | Placebo beetroot juice (equivalent volume to the amount of nitrate-rich beetroot juice consumed) daily for 8 weeks. Receives: Other: Placebo beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in blood pressure measure
Systolic blood pressure, diastolic blood pressure and pulse pressure
Measured: Before and after each 8 week intervention
Change in oral bacteria composition
Oral bacteria composition determined using next generation sequencing.
Measured: Before and after each 8 week intervention
Secondary outcomes (12)
Change in vascular reactivity
Laser Doppler Imaging with iontophoresis.
Measured: Before and after each 8 week intervention
Change in Nox concentrations in serum, urine and saliva
Nitrate and nitrite concentrations will be determined using high performance liquid chromatography in plasma, urine and saliva. Nitric oxide will be calculated as the sum of nitrate and nitrite concentrations.
Creatinine will be measured in the urine samples to normalise the nitrate and nitrite concentrations in urine for hydration status.
Measured: Before and after each 8 week intervention
Change in gut bacteria composition
Stool sample will be analysed to determine composition using next generation sequencing will be used to find the differences between treatments.
Measured: Before and after each 8 week intervention
Change in fasting lipid profile
Total cholesterol, HDL-C, and triacylglycerol will be measured using a clinical chemistry analyser. LDL-C will be calculated using the Friedewald formula.
Measured: Before and after each 8 week intervention
Change in C-reactive protein
C-reactive protein will be measured using a clinical chemistry analyser
Measured: Before and after each 8 week intervention
Change in endothelial function
Pulse wave analysis will be measured using Mobil-O-Graph
Measured: Before and after each 8 week intervention
Change in body weight
Body weight will be measured using a Tanita scale
Measured: Before and after each 8 week intervention
Height measurement
Height will be measured using a stadiometer
Measured: Before the intervention
Change in body mass index
Body mass index will be calculated from the body weight and height measurement
Measured: Before and after each 8 week intervention
Change in insulin
Insulin levels will be measured by ELISA
Measured: Before and after each 8 week intervention
Change in glucose
Glucose levels will be measured using a clinical chemistry analyser
Measured: Before and after each 8 week intervention
Change in insulin sensitivity
Glucose and insulin measurements will be used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR)
Measured: Before and after each 8 week intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2018
- Study start1 Dec 2018
- Primary completion1 Dec 2020
- Study completion1 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for No Dental DiseaseStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Reading
- Sponsor type
- University, hospital or other
- Collaborators
- Saudi Cultural Bureau
- Responsible party
- Principal investigator, Julie Lovegrove, University of Reading
- Investigators
- Julie A Lovegrove, BSc, PhD, Principal investigator, University of Reading
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03784742
- Sponsor's protocol ID
- 347890
- Acronym
- REBOC2
- Status last verified
- Apr 2024
- First submitted
- 1 Nov 2018
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Effects of Daily Nitrate Consumption on Oral Bacteria Composition, Blood Pressure and Vascular Functio
- ClinicalTrials.gov ID
- NCT03784742
- Acronym / sponsor ID
- REBOC2 / 347890
- Conditions
- No Dental Disease, Non-smoking
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of ReadingUniversity, hospital or other
- Collaborators
- Saudi Cultural Bureau
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 24 Dec 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.
Diseases of the heart and blood vessels, including raised blood pressure, are one of the leading causes of death worldwide. Higher intakes of dietary nitrate, found abundantly in root vegetables such as beetroot, have been shown to have health benefits including lowering blood pressure and improving the elasticity of blood vessels. Bacteria which reside in the mouth and those in the gastrointestinal tract play an important role in converting dietary nitrate to nitrite and nitric oxide (a chemical which promotes the relaxation of blood vessels). In particular, removal of oral bacteria by using antiseptic mouthwash is accompanied by an increase in blood pressure in subjects with normal blood pressure, even after consuming nitrate-rich foods. To date, very little is known about the role of these oral bacteria in the control of blood pressure, and if there are any differences in bacterial composition between individuals.
Detailed description
Interested volunteers will be provided with an outline of the study and asked to complete a medical and lifestyle questionnaire (in person, by email or over the phone). Potentially suitable participants will be identified and asked to attend a screening session after a 12 h overnight fast (not eating during this time and only drinking water) during which the study will be explained in more detail before a consent form is signed. Anthropometric measurements will then be taken including weight, height and blood pressure. A 9 ml blood sample will also be collected on site at the Department of Food and Nutritional Sciences (Hugh Sinclair Unit of Human Nutrition). Subjects who meet the initial inclusion criteria will be invited to a further screening session during which time a dentist will check for dental diseases (e.g. current dental cavities or periodontal infection) and saliva flow rate. Volunteers without periodontal disease and with normal saliva flow will then be invited to participate in the study.
Eligible subjects will then be randomised to one of two treatments: i) up to 70 ml (the amount given will be equivalent to 3.7 mg/kg body weight) beetroot juice (James White Drinks Limited, UK) or ii) a matched volume of placebo beetroot juice (control, James White Drinks Limited, UK) to be consumed daily for 8 weeks. As drinking water is a major source of dietary nitrate, subjects will be provided with a water filter to reduce the nitrate level in their tap water for drinking and cooking during the study period. There will be a wash out period of 4 weeks between the intervention juices. In total, volunteers will be involved in the study for 20 weeks (five months).
On the day before each baseline study visit (weeks 0 and 12), volunteers will be required to fast overnight after having a low nitrate evening meal and only drinking low nitrate mineral water (Buxton mineral water), which will be provided to them, during this time. They will refrain from strenuous exercise and alcohol. On the morning of the study visit, the volunteers will be asked not to brush their teeth before they come to the clinical unit for their study visit.
When they arrive in the fasted state, the participants will be asked to provide a spot urine sample and a stool sample. Body weight and composition will be measured using the Tanita weighing scale, saliva sample and an oral bacteria sample will be collected by swabbing the tongue with a cotton swab. Volunteers will be asked to lie down for 20 minutes prior to the measurement of blood pressure and pulse wave analysis (PWA) using the Mobil-O-Graph device followed by the assessment of microvascular reactivity using Laser Doppler Imaging with iontophoresis. A blood sample of 20 ml (equivalent to just over 1 tablespoon) will then be taken before a light breakfast is provided. Volunteers will then be given a toothbrush and toothpaste to brush their teeth and asked to complete an online food frequency questionnaire (EatwellUK).
During the four-week wash-out period between interventions, participants will be instructed to avoid any beetroot juice drinks and maintain their usual dietary and lifestyle habits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrate-rich Beetroot juice | Active comparator | Other: Nitrate rich beetroot juiceNitrate-rich beetroot juice equivalent to 3.7 mg nitrate per kg body weight daily for 8 weeks. |
| Placebo beetroot juice | Placebo comparator | Other: Placebo beetroot juicePlacebo beetroot juice (equivalent volume to the amount of nitrate-rich beetroot juice consumed) daily for 8 weeks. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male and female;
- A signed consent form;
- Blood pressure <140/90 mm Hg;
- BMI range 18.5 - 39.9 kg/m2;
- Age 18-64 years;
Key exclusion criteria (12 listed)
- Diagnosed with a chronic illness;
- Anaemia defined as a haemoglobin < 115 g/l for women and <130 g/l for men;
- Individuals with food allergies or allergies to medicated mouthwash or ingredients in the oral products;
- Requirements to take long-term medication active on the oral cavity including prebiotics and probiotics or have taken antibiotics within the last 3 months;
- Gingivitis diagnosis, or periodontal disease or chronic oral complaints or existing oral pathology.
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 |
|---|---|---|
| Nitrate rich beetroot juiceJames White Drinks Limited beetroot juice (0.4-0.45 g nitrate/70 ml drink). | Other | Nitrate-rich Beetroot juice |
| Placebo beetroot juiceJames White Drinks Limited Placebo beetroot juice (0 nitrate/70 ml drink). | Other | Placebo beetroot juice |
Primary outcome
Change in blood pressure measure
Time frame: Before and after each 8 week intervention
Systolic blood pressure, diastolic blood pressure and pulse pressure
Change in oral bacteria composition
Time frame: Before and after each 8 week intervention
Oral bacteria composition determined using next generation sequencing.
12 secondary outcomes
Change in vascular reactivity
Time frame: Before and after each 8 week intervention
Change in Nox concentrations in serum, urine and saliva
Time frame: Before and after each 8 week intervention
Change in gut bacteria composition
Time frame: Before and after each 8 week intervention
Change in fasting lipid profile
Time frame: Before and after each 8 week intervention
Change in C-reactive protein
Time frame: Before and after each 8 week intervention
Change in endothelial function
Time frame: Before and after each 8 week intervention
Change in body weight
Time frame: Before and after each 8 week intervention
Height measurement
Time frame: Before the intervention
Change in body mass index
Time frame: Before and after each 8 week intervention
Change in insulin
Time frame: Before and after each 8 week intervention
Change in glucose
Time frame: Before and after each 8 week intervention
Change in insulin sensitivity
Time frame: Before and after each 8 week 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 12 Apr 2024.
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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.
Julie A Lovegrove, BSc, PhD principal investigator
University of Reading
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitrate rich beetroot juice in people with No Dental Disease and Non-smoking, run by University of Reading 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 8 inclusion and 12 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 12 Apr 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 in blood pressure measure (time frame: Before and after each 8 week intervention). The study lists 2 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 12 Apr 2024.