Role of the Oral Microbiome in Blood Pressure Regulation in Pregnancy

NCT03930693 | Completed

• 1 other identifier: 246813
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

High blood pressure in pregnancy is associated with poor outcomes for both mum and baby, increasing the risk of pregnancy complications including pre-eclampsia, fetal growth restriction and preterm birth. The development of new blood pressure lowering interventions suitable for use in pregnancy is a key research priority. Inorganic nitrate is a compound found in certain types of food, particularly green leafy vegetables and beetroot. Nitrate provides an important source of nitric oxide (NO), a molecule involved in keeping blood vessels healthy and regulating blood pressure. Supplementation with nitrate in the diet, using interventions such as beetroot juice, has been shown to reduce blood pressure and improve blood vessel function. In order for dietary nitrate to have these beneficial effects, it needs to be converted in the body to nitrite, via bacteria that live in the mouth (oral bacteria). Differences in oral bacteria, and how they metabolise nitrate, are thought to influence blood pressure regulation and potentially response to dietary nitrate supplementation. This study aims to understand (1) whether pregnant women with high blood pressure have a different composition of oral bacteria compared to healthy pregnant women and women who are not pregnant, and (2) how differences in oral bacteria affect blood pressure responses to a dose of dietary nitrate (in the form of beetroot juice).

Conditions

Gestational Hypertension

Keywords

Pregnancy; hypertension; nitrate; beetroot juice

Outcome Measures

Primary Outcomes (3)

• Quantity of oral nitrate reducing bacterial species

  Assessment of oral bacterial profile using next-generation sequencing (bacterial 16S rRNA sequencing)

  Baseline

• Oral bacterial nitrate reductase activity

  Assessment of oral nitrate reductase activity, measured using enzyme assay

  Baseline

• Difference between groups in nitrate/nitrite concentrations before and after dietary nitrate dose

  Measurement of plasma and salivary nitrate and nitrite concentrations, using high-performance liquid chromatography (HPLC)

  Baseline to 2.5 hour post-nitrate dose

Secondary Outcomes (1)

• Difference between groups in blood pressure response to dietary nitrate dose

  Baseline to 2.5 hour post-nitrate dose

Other Outcomes (2)

• Correlation between salivary nitrate reductase activities and the change in salivary/plasma nitrite concentrations post-nitrate dose

  Baseline to 2.5 hour post-nitrate dose

• Correlation between changes in plasma nitrite concentrations and blood pressure lowering post-nitrate dose

  Baseline to 2.5 hour post-nitrate dose

Study Arms (4)

Normotensive pregnant women

EXPERIMENTAL

Normotensive pregnant women

Dietary Supplement: Beetroot juice

Hypertensive pregnant women

EXPERIMENTAL

Hypertensive pregnant women

Dietary Supplement: Beetroot juice

Normotensive non-pregnant women

EXPERIMENTAL

Normotensive non-pregnant women

Dietary Supplement: Beetroot juice

Hypertensive non-pregnant women

EXPERIMENTAL

Hypertensive non-pregnant women

Dietary Supplement: Beetroot juice

Interventions

Beetroot juice DIETARY_SUPPLEMENT

Beetroot juice shot (70mL containing 400mg inorganic nitrate)

Hypertensive non-pregnant women; Hypertensive pregnant women; Normotensive non-pregnant women; Normotensive pregnant women

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Normotensive or hypertensive women (hypertension as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg OR on anti-hypertensive medication)
• For pregnant women, between 20-28 weeks gestation

You may not qualify if:

• Multi-fetal pregnancy (for pregnant women)
• Age under 16, or over 45 years of age
• Lacking ability to consent
• Pre-existing diabetes (Type 1/Type 2)
• Previous history of pre-term FGR (delivery before 32 weeks with FGR)
• Current tobacco smoker
• Body Mass Index greater than or equal to 40 or less than or equal to 18
• Use of any of the following drugs in the last 6 months: systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral)
• Large doses of commercial probiotics (greater than or equal to 108 cfu or organisms per day) including tablets, capsules, lozenges, chewing gum or powders (ordinary dietary components such as yoghurts do not apply)
• Evidence of oral disease, assessed on screening proforma (current conditions of: oral candidiasis (thrush); Dental caries (tooth decay); Halitosis; Oral ulcerations/mouth ulcers; Wisdom tooth pain; Chronic dry mouth)
• Allergy to beetroot juice or lemon juice (both contained within the juice shot)

Sponsors & Collaborators

• University of Manchester: lead

Study Sites (1)

Maternal and Fetal Health Research Centre, St Mary's Hospital

Manchester, United Kingdom

Location

Related Publications (1)

• Willmott T, Ormesher L, McBain AJ, Humphreys GJ, Myers JE, Singh G, Lundberg JO, Weitzberg E, Nihlen C, Cottrell EC. Altered Oral Nitrate Reduction and Bacterial Profiles in Hypertensive Women Predict Blood Pressure Lowering Following Acute Dietary Nitrate Supplementation. Hypertension. 2023 Nov;80(11):2397-2406. doi: 10.1161/HYPERTENSIONAHA.123.21263. Epub 2023 Sep 13.

  PMID: 37702047 DERIVED

MeSH Terms

Conditions

Hypertension, Pregnancy-Induced; Hypertension

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jenny Myers, BM, PhD

  Manchester University NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Beetroot juice intervention given to all participants (1 dose only)

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 29, 2019
• Study Start: June 6, 2019
• Primary Completion: July 12, 2021
• Study Completion: March 31, 2022
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)