Inorganic Nitrate Supplementation in Chronic Hypertensive Pregnancies

NCT06105775 | Recruiting

• 1 other identifier: 21/12010-7-SP2
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

High blood pressure during pregnancy poses significant risks to both the mother and baby. A combination of factors, including advancing maternal age, rising obesity rates, and metabolic health issues, have amplified the prevalence of this condition. While conventional medicines are available, safety during pregnancy remains a concern. Recent studies suggest that inorganic nitrate might be a safer alternative. The power of nitrate lies in its ability to stimulate the body's production of a compound that aids in dilating and relaxing blood vessels. Preliminary studies conducted on mice and a select group of pregnant women have yielded encouraging results. Early tests indicated that after consuming inorganic nitrate, there was a reduction in blood pressure and an improvement in the health of the mother's uterine artery-a vital vessel responsible for nourishing the fetus. Our study aims to investigate the effects of inorganic nitrate supplementation on pregnant women from the start of their pregnancy and continuing it throughout their term. If our findings are positive, it could revolutionize how we approach blood pressure management during pregnancy, paving the way for healthier futures for both mothers and babies.

Conditions

Hypertension in Pregnancy; Hypertension; Pregnancy

Keywords

Endothelial Dysfunction; Hypertension in Pregnancy; Nitric Oxide; inorganic nitrate

Outcome Measures

Primary Outcomes (2)

• Blood Pressure Control in Chronic Hypertensive Pregnant Women with Inorganic Nitrate Supplementation Compared to Placebo.

  Blood pressure will be assessed using semiautomatic equipment, measuring systolic and diastolic pressures in millimeters of mercury (mmHg). Ambulatory Blood Pressure Monitoring (ABMP) will be employed at the beginning of the clinical trial. Lower readings indicate better blood pressure control, while higher readings suggest poorer control.

  From baseline (16th week) up to delivery

• Increased Antihypertensive Medication Requirements in Patient Groups

  The investigators will monitor both the inorganic nitrate group and the placebo group for any need to increase the dosage of antihypertensive medications, frequency or introduce a new agent.

  From baseline (16th week) up to delivery

Secondary Outcomes (12)

• Doppler Analysis of Maternal and Fetal Vessel Behavior Across Pregnancy in Both Groups

  From baseline (16th week) up to delivery

• Fetal Growth Assessment and Incidence of Fetal Growth Restriction in Both Groups

  From baseline (16th week) up to delivery

• Incidence of Preeclampsia Overlap and Adverse Maternal Outcomes in Each Group

  At the time of delivery

• Incidence of Perinatal Outcomes

  Immediately after delivery.

• Vascular Reactivity of the Umbilical Artery In Vitro in Both Groups After Delivery

  Approximately 15 to 30 minutes post-delivery, with some additional time for the in vitro evaluations.

Study Arms (2)

Inorganic Nitrate Capsule

EXPERIMENTAL

Once daily capsule containing sodium nitrate (400 mg of nitrate and 140 mg of sodium), for 154 consecutive days.

Dietary Supplement: Inorganic Nitrate Capsule

Placebo Capsule.

PLACEBO COMPARATOR

Once daily capsule containing sodium chloride (140 mg of sodium chloride and 400 mg of flour), for 154 consecutive days.

Dietary Supplement: Placebo Capsule

Interventions

Inorganic Nitrate Capsule DIETARY_SUPPLEMENT

Starting from the 16th week of gestation and continuing for 22 weeks (154 days) or until delivery, whichever comes first, participants will consume a daily capsule containing 400 mg of inorganic nitrate. Participants will maintain standard preeclampsia prophylaxis (acetylsalicylic acid 100mg nightly until 36 weeks of gestation and calcium carbonate 1000mg daily until delivery) and regular antihypertensive treatment.

Inorganic Nitrate Capsule

Placebo Capsule DIETARY_SUPPLEMENT

From the 16th week of gestation and lasting 22 weeks (154 days) or until delivery, participants will consume a daily capsule containing sodium chloride with the nitrate replaced by plant-based flour, design to mimic the appearance of the active capsule. Participants will maintain standard preeclampsia prophylaxis (acetylsalicylic acid 100mg nightly until 36 weeks of gestation and calcium carbonate 1000mg daily until delivery) and regular antihypertensive treatment.

Placebo Capsule.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women diagnosed with chronic hypertension (systolic blood pressure above 140 mmHg and/or diastolic blood pressure above 90 mmHg before pregnancy or before 20 weeks of gestation) as defined by the Brazilian Network for Studies on Hypertension in Pregnancy (RBEHG, Brazilian acronym) Protocol and Chronic Hypertension/Preeclampsia by the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO, Brazilian acronym) Protocol.
• Women with less than 16 weeks of gestation confirmed by first-trimester ultrasonography confirming gestational age.

You may not qualify if:

• Multiple pregnancies, age below 18 years old, inability to provide informed consent, or history of low adherence to medication therapy.
• Patients with uncontrolled chronic hypertension, with blood pressure values above 160x110mmHg.
• History of food allergies, especially hypersensitivity to beetroot.
• Users of illicit drugs, smokers, or alcohol abusers.
• Diagnosis of coronary artery disease, congestive heart failure (moderate to severe), moderate to severe liver failure, chronic renal insufficiency (with plasma creatinine clearance less than 30 ml/min/1.73 m² of body surface), pre-existing type 1 diabetes, and type 2 diabetes.
• Pregnant women who frequently used non-steroidal anti-inflammatory drugs, nasal decongestants, and anorectics before getting pregnant; users of proton pump inhibitors and H2 receptor antagonists or any other medication that interferes with stomach pH, starting 2 weeks before the beginning and continuing throughout the remainder of the study.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Hospital das Clínicas de Ribeirão Preto: collaborator

Study Sites (1)

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP

Ribeirão Preto, São Paulo, Brazil

RECRUITING

Related Publications (1)

• Oliveira Barbosa P, Aniceto V, Lima-Junior LS, de Souza Costa A, Tanus-Santos JE, Sandrim VC, Carvalho Cavalli R. NIT_CH: A study protocol for evaluating the effect of inorganic nitrate capsules in chronic hypertensive pregnancies - a triple-blind placebo-controlled randomized trial. BMC Pregnancy Childbirth. 2026 Jan 9;26(1):136. doi: 10.1186/s12884-025-08596-8.

  PMID: 41514223 BACKGROUND

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

• Ricardo C Cavalli, Dr

  Medical School of Ribeirao Preto, USP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ricardo C Cavalli, Dr

CONTACT

+55166021000; rcavalli@fmrp.usp.br

Priscila O Barbosa, Dr

CONTACT

+5531971349289; barbosapo@usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 30, 2023
• Study Start: March 6, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)