Inorganic Nitrate Supplementation in Chronic Hypertensive Pregnancies (NIT_CH)

University of Sao Paulo

Status: Enrolling

Conditions: Hypertension; Hypertension in Pregnancy; Pregnancy

Treatments: Dietary Supplement: Inorganic Nitrate Capsule; Dietary Supplement: Placebo Capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT06105775

21/12010-7-SP2

Details and patient eligibility

About

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.

Full description

Eligible pregnant women with chronic hypertension will be identified and invited to participate through posters displayed in the municipality's health units, as well as by medical professionals within the local health network, based on the inclusion criteria. An appointment will be promptly scheduled to verify eligibility and present the informed consent form, during which all questions and concerns will be addressed.

On the enrollment day, the subsequent visit will be scheduled for the 16th week of their pregnancy, marking the commencement of the study. By then, participants will already have been randomly allocated to respective groups by an external professional who is not directly involved in the study, ensuring blinding. Randomization will occur on a 1:1 ratio, employing blocks of 2-4 pregnant women as determined by specialized software. Regardless of allocation, participants will continue with standard medications for preeclampsia prophylaxis: acetylsalicylic acid, taken at 100 mg nightly up to 36 weeks of gestation, and calcium carbonate, taken at 1000 mg daily until delivery, alongside routine antihypertensive treatment.

From the 16th week of pregnancy onward, participants will receive either a capsule containing 400 mg of inorganic nitrate (540 mg of sodium nitrate, equivalent to 140 mg of sodium chloride and 400 mg of nitrate) or a placebo (140 mg of sodium chloride and 400 mg of flour). Both capsules will be identical in color and appearance. All participants will be instructed to take one capsule each morning, continuing this regimen for 22 weeks (154 days), ending either at the 38th week of pregnancy or at childbirth, whichever occurs first.

Visits will take place at predetermined intervals based on the progression of the pregnancy. Initially set at a frequency of every 4 weeks, but as the end of the pregnancy approaches, the visits will become more frequent. The baseline appointment is set for the 16th week of gestation, with subsequent appointments scheduled for the 20th, 24th, 28th, 32nd, 34th, 36th, 37th, and 38th weeks. It is important to note that scheduled visits may conclude earlier if childbirth occurs sooner, or they might be extended if the pregnancy progresses beyond the anticipated delivery date. During these visits, participants will undergo an obstetric clinical examination, blood pressure measurement, biochemical analysis, and an ultrasound paired with a Doppler study of the uterine arteries.

To ensure consistent and optimal blood pressure levels, the overseeing medical team will closely monitor and adjust participants' antihypertensive medications as necessary. Ensuring adherence to the regimen is paramount; thus, participants will be asked to return any unused capsules during their visits and will then be supplied with their next batch for the ensuing period.

Enrollment: 144 estimated patients

Sex: Female

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.
• Patients on monotherapy with methyldopa as treatment at the time of inclusion.
• Women with less than 16 weeks of gestation confirmed by first-trimester ultrasonography confirming gestational age.

Exclusion criteria

• Multiple pregnancies, age below 16 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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144 participants in 2 patient groups, including a placebo group

Inorganic Nitrate Capsule

Experimental group

Description:

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

Treatment:

Dietary Supplement: Inorganic Nitrate Capsule

Placebo Capsule.

Placebo Comparator group

Description:

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

Treatment:

Dietary Supplement: Placebo Capsule