Dietary Nitrate and the Oral Microbiome in Children With Primary Hypertension

NCT07236125 | Not Yet Recruiting DMC

• 1 other identifier: 2025/169
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Children and adolescents with primary hypertension (high blood pressure without an underlying secondary cause) are at increased risk of cardiovascular disease in adulthood. Recent research suggests that not only the heart and blood vessels, but also the bacteria living in the mouth may play a role in blood pressure regulation. Certain oral bacteria can convert nitrate from food into nitrite and then into nitric oxide, a substance that helps blood vessels relax. If this nitrate-nitrite-nitric oxide pathway is impaired, blood pressure may rise. This study aims to investigate the relationship between oral microbiota, salivary nitric oxide reductase activity and blood pressure in children and adolescents with primary hypertension compared with healthy peers. We will recruit participants aged 12-18 years who have a diagnosis of primary hypertension and an age- and sex-matched control group without hypertension. All participants will undergo a non-invasive oral and dental examination and standardized blood pressure measurements. Saliva samples will be collected to measure pH, flow rate, nitrate and nitrite levels, total protein, lysozyme activity and to analyze the composition of oral bacteria using modern DNA-based techniques. Participants and/or their parents will also complete brief questionnaires about diet and general health. No medication or dietary supplement will be given as part of the study, and no additional blood samples will be taken beyond routine clinical care. The main risk is minimal discomfort related to oral examination and saliva collection. There is no guaranteed direct benefit for participants; however, the results may help us better understand how oral bacteria and salivary nitric oxide pathways are linked to high blood pressure in young people. This knowledge may support the development of new non-invasive strategies for early detection and prevention of hypertension in the future.

Conditions

Primary Hypertension

Keywords

primary hypertension; oral microbiome; nitrate-reduction bacteria; salivary nitrite; salivary nitrate; pediatric hypertension; Enterosalivary Nitrate Cycle; Adolescent Hypertension; Salivary Microbiome; Nitrate-Nitrite-Nitric Oxide Pathway; Saliva Biomarkers; Endothelial Dysfunction; Blood Pressure in Adolescents; Non-invasive Biomarkers; Saliva-Based Diagnostics

Outcome Measures

Primary Outcomes (1)

• Microbiota Composition (16S rRNA Sequencing)

  Characterization of bacterial community diversity and relative abundance in unstimulated saliva using 16S rRNA gene sequencing. Analysis will include alpha diversity, beta diversity, and differential taxa abundance between groups, with a focus on nitrate-reducing genera such as Neisseria, Rothia, and Actinomyces.

  Baseline

Secondary Outcomes (4)

• Salivary Nitrate and Nitrite Levels

  Baseline (single visit)

• Salivary pH

  Baseline

• Salivary Flow Rate

  baseline

• Salivary Lysozyme Activity

  baseline

Study Arms (2)

Patients with primary hypertension

This group includes adolescents aged 12-18 years who have been clinically diagnosed with primary hypertension based on repeated office blood pressure measurements according to pediatric hypertension guidelines. Participants will undergo standardized assessments including oral examination, blood pressure measurements, salivary collection, and laboratory analyses. Laboratory procedures include: oral microbiota profiling through 16S rRNA gene sequencing, quantification of nitrate-reducing bacterial activity, measurement of salivary pH, total protein concentration, and lysozyme activity. No therapeutic intervention will be administered. All procedures are observational and aim to characterize microbial and biochemical markers associated with primary hypertension.

Other: No active intervention

Healthy controls

This group includes healthy adolescents aged 12-18 years with no history of primary or secondary hypertension, chronic systemic disease, or regular medication use affecting cardiovascular or oral microbiome physiology. Participants will undergo standard clinical assessments identical to the hypertension group, including oral examination, salivary collection, and blood pressure measurement. Laboratory procedures will include salivary microbiota analysis (16S rRNA sequencing), assessment of nitrate-reducing bacterial activity, salivary pH, total protein concentration, and lysozyme activity. This cohort serves as the normative comparison group to evaluate microbial and biochemical differences associated with primary hypertension. No intervention will be administered.

Other: No active intervention

Interventions

No active intervention OTHER

This is an observational study with no active intervention. No drug, device, behavioral, dietary, surgical, or diagnostic intervention is administered to participants. All study procedures, including oral examination, salivary sampling, pH measurement, biochemical tests, and blood pressure assessment, are non-interventional and part of standard clinical evaluation. The study only aims to observe natural variations in oral microbiota composition, nitrate-reducing activity, and blood pressure without changing participants' medical care.

Healthy controls; Patients with primary hypertension

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from children and adolescents aged 12-18 years presenting to the Istanbul University Faculty of Dentistry, Department of Pediatric Dentistry, as well as pediatric patients followed by the Pediatric Nephrology Clinic who have been diagnosed with primary hypertension. The study population includes two groups: (1) adolescents with confirmed primary hypertension, not on antihypertensive medication, and (2) age- and sex-matched healthy controls without systemic disease or blood pressure abnormalities. All participants will be systemically healthy, cooperative, and able to provide saliva samples, undergo oral examinations, and complete questionnaire assessments. Recruitment will be consecutive based on clinic attendance, and all participants and their families will be informed about study procedures before enrollment.

You may qualify if:

• Applied to the Istanbul University Faculty of Medicine, Department of Pediatric Nephrology,
• Between the ages of 12 and 18,
• Diagnosed with primary hypertension,
• Clinically excluded from secondary hypertension or heart failure,
• No systemic or chronic disease other than hypertension,
• No periodontal disease, dental infection, or oral mucosal disease,
• Not taking regular antihypertensive or other medications for a chronic disease,
• Not having received antibiotic treatment in the last 3 months,
• Patients who have not used mouthwash in the last 3 months,
• Have no allergies to nitrate-rich foods,
• Both male and female patients will be included.

You may not qualify if:

• Younger than 12 years of age or older than 18 years of age
• Clinically diagnosed with secondary hypertension or heart failure
• Have a systemic disease
• Have periodontal disease, dental infection, or oral mucosal disease
• Are taking regular antihypertensive medications or other chronic illnesses
• Have received antibiotic treatment within the last 3 months
• Have used mouthwash within the last 3 months
• Are allergic to nitrate-rich foods will not be included in the study.

Sponsors & Collaborators

• Yelda Kasımoğlu: lead
• Istanbul University Scientific Research Projects Coordination Unit- Pending: collaborator

Study Sites (1)

Istanbul University Faculty of Dentistry

Istanbul, Fatih, 34093, Turkey (Türkiye)

Location

Related Publications (3)

• Li D, Nishi SK, Jovanovski E, Zurbau A, Komishon A, Mejia SB, Khan TA, Sievenpiper JL, Milicic D, Jenkins A, Vuksan V. Repeated administration of inorganic nitrate on blood pressure and arterial stiffness: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2020 Nov;38(11):2122-2140. doi: 10.1097/HJH.0000000000002524.

  PMID: 32723980 RESULT

• Broxterman RM, La Salle DT, Zhao J, Reese VR, Richardson RS, Trinity JD. Influence of dietary inorganic nitrate on blood pressure and vascular function in hypertension: prospective implications for adjunctive treatment. J Appl Physiol (1985). 2019 Oct 1;127(4):1085-1094. doi: 10.1152/japplphysiol.00371.2019. Epub 2019 Aug 15.

  PMID: 31414959 RESULT

• Carey RM, Wright JT Jr, Taler SJ, Whelton PK. Guideline-Driven Management of Hypertension: An Evidence-Based Update. Circ Res. 2021 Apr 2;128(7):827-846. doi: 10.1161/CIRCRESAHA.121.318083. Epub 2021 Apr 1.

  PMID: 33793326 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Unstimulated whole saliva samples will be collected from all participants using sterile collection tubes. Aliquots of each sample will be stored at -80°C for downstream laboratory analyses. These biospecimens will be used for: * Genomic DNA extraction for 16S rRNA gene sequencing to characterize the oral microbiota, * Quantification of nitrate-reducing bacterial activity, * Measurement of salivary biomarkers, including pH, total protein concentration, and lysozyme activity. All retained samples contain DNA and will be used exclusively for research analyses within the scope of this protocol. No leftover samples will be used for commercial purposes.

MeSH Terms

Conditions

Essential Hypertension

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Yelda Kasimoglu Assoc. Prof.

CONTACT

+90 533 623 39 78; yelda.kasimoglu@iu.edu.tr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assoc. Prof.

Study Record Dates

• First Submitted: November 15, 2025
• First Posted: November 19, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)