Beetroot Juice Supplementation in Chronic Hypertensive Pregnancies

Hypertension Clinical Trial

— BEET_CH  

Official title:

Beetroot Juice Supplementation for Blood Pressure Management in Chronic Hypertensive Pregnancies From the 2nd Trimester (BBET_CH): a Triple-Blind, Randomized, Placebo-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06105775
• Other study ID #: 21/12010-7-SP2
• Status: Recruiting
• Phase: N/A
• Start date: February 19, 2024
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: University of Sao Paulo
• Contact: Ricardo C Cavalli, Dr
• Phone: +55166021000
• Email: rcavalli[@]fmrp.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 beetroot might be a safer alternative. The efficacy of beetroot is attributed to its ability to stimulate the body's production of a natural 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 beetroot supplements, 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. The study aims to delve deeper by evaluating the effects of beetroot juice on pregnant women from the beginning of pregnancy and continuing it throughout the term. If the results are positive, beetroot could revolutionize the approach to blood pressure management during pregnancy, paving the way for healthier futures for both mothers and their babies.

Description:

Eligible hypertensive pregnant women will be identified and approached for participation by medical professionals within the municipality's 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, 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 pre-eclampsia 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 either receive a shot of nitrate-enriched concentrated beetroot extract (Beet-It Sport®; James White Drinks Co, UK), or an equivalent placebo. All participants will be instructed to consume the entire content (70ml) each morning, continuing this regimen for a period of 22 weeks (154 days), ending either at the 38th week of pregnancy or 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 shots during their visits and will then be supplied with the next batch for the ensuing period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: March 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

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.
• Pregnant women with a body mass index above 40 kg/m².
• 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.

Related Conditions & MeSH terms

• Hypertension
• Hypertension in Pregnancy
• Hypertension, Pregnancy-Induced
• Pregnancy

Intervention

Dietary Supplement:
• Nitrate-enriched beetroot extract juice
Starting from the 16th week of gestation, participants will consume a daily 70 ml of nitrate-enriched beetroot extract (Beet-It Sport®, James White Drinks Co, UK) for 22 weeks or until delivery, whichever comes first. The extract contains approximately 6.5mmol of nitrate (~400mg). Participants will also continue with standard pre-eclampsia prophylaxis (acetylsalicylic acid 100mg nightly until the 36th week and calcium carbonate 1000mg daily) and their usual antihypertensive treatment.
• Placebo juice
Starting from the 16th week of gestation and continuing for either 22 weeks (154 days) or until delivery, participants will consume a daily 70ml of placebo. This is designed to mimic the appearance and taste of the beetroot extract and will be bottled identically. Concurrently, participants will continue their standard pre-eclampsia prophylaxis, which includes acetylsalicylic acid 100mg nightly until the 36th week of gestation and calcium carbonate 1000mg daily until delivery, alongside their regular antihypertensive treatment.

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP	Ribeirão Preto	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Hospital das Clínicas de Ribeirão Preto

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Pressure Control with Beetroot Juice Supplementation in Chronic Hypertensive Pregnant Women	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
Primary	Increased Antihypertensive Medication Requirements in Patient Groups	The investigators will monitor both the beetroot juice-supplemented and placebo groups for any need to increase the dosage of antihypertensive medications, frequency or introduce a new agent.	From baseline (16th week) up to delivery
Secondary	Doppler Analysis of Maternal and Fetal Vessel Behavior Across Pregnancy in Both Groups	Using Doppler velocimetry, the investigators will evaluate fetal vessels, focusing on the middle cerebral artery and umbilical artery. These tests will be conducted with mothers resting in left lateral decubitus during fetal rest periods, excluding respiratory movements. Key parameters, including the systole/diastole (A/B) ratios, resistance index, and pulsatility index, will be captured. Concurrently, maternal Doppler velocimetry of the uterine artery and pulse wave velocity will be measured to assess arterial stiffness.	From baseline (16th week) up to delivery
Secondary	Fetal Growth Assessment and Incidence of Fetal Growth Restriction in Both Groups	Fetal growth will be assessed using biometric measurements and evaluations like the fetal biophysical profile, placental maturity grade, and amniotic fluid evaluations. Key biometric parameters include biparietal diameter, cranial circumference, abdominal circumference, femur length, and estimated fetal weight (EFW). The "Hadlock" formula will help determine EFW, classifying the fetus as small for gestational age, average or large for gestational age. The biophysical profile will give insights into fetal movements and conditions over a 30-minute period. Placental maturity and amniotic fluid status will further provide context to the overall fetal health and growth.	From baseline (16th week) up to delivery
Secondary	Incidence of Preeclampsia Overlap and Adverse Maternal Outcomes in Each Group	Clinical data will be collected to evaluate the presence of preeclampsia overlap and any associated adverse maternal outcomes. The collected data will include the gestational age at the time of delivery (in weeks + days), type of delivery (vaginal or cesarean), and specific clinical outcomes related to the mother's health	At the time of delivery
Secondary	Incidence of Perinatal Outcomes	Post childbirth, perinatal outcomes will be assessed by recording essential metrics of the newborn. The collected data will include the newborn's gender, weight (measured in grams), length (measured in cm), and the Apgar scores documented at both the first- and fifth minutes post-birth.	Immediately after delivery.
Secondary	Vascular Reactivity of the Umbilical Artery In Vitro in Both Groups After Delivery	Umbilical cord fragments will b collected for evaluation. The fragments will be used to assess vascular tone changes in the umbilical artery using isometric force transducers. The viability and reactivity of the vessel rings will be determined using specific stimuli such as potassium chloride (KCl) and serotonin.	Approximately 15 to 30 minutes post-delivery, with some additional time for the in vitro evaluations.
Secondary	Evaluation of Complete Blood Count, Lipid and Glycemic Profiles, and Fasting Insulin Levels in Each Group	Participants' overall health will be evaluated through a series of blood tests, including complete blood count, glucose and insulin levels, creatinine, urea, liver enzymes, serum bilirubins and lipid profile.	From baseline (16th week) up to delivery
Secondary	Evaluation of Nitric Oxide Metabolite Concentrations in Plasma, Urine, and Saliva in Each Group	The concentrations of nitrate and nitrite, as key metabolites of nitric oxide, will be assessed in participants' plasma, urine, and saliva samples. The determination will be done using the Sievers Nitric Oxide Analyzer	From baseline (16th week) up to delivery
Secondary	Evaluation of Serum Markers for Preeclampsia in Each Group	The risk of developing preeclampsia will be assessed by calculating the soluble fms-like tyrosine kinase (sFLT-1) and placenta growth factor (PlGF) ratio using serum values of the angiogenic factors PlGF and sFLT-1. This ratio provides an indication of the likelihood of preeclampsia onset within specified time frames or the presence of placental insufficiency.	From baseline (16th week) up to delivery
Secondary	Evaluation of Inflammatory Markers in Each Group	Serum concentrations of various inflammatory markers, including adiponectin, intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL6), interleukin-8 (IL8), interleukin-10 (IL10), leptin, resistin, tumor necrosis factor-alpha (TNFa), vascular cell adhesion molecule 1 (VCAM-1), vascular endothelial growth factor (VEGF), and visfatin, will be determined to evaluate inflammatory status in the participants.	From baseline (16th week) up to delivery
Secondary	Evaluation of Oxidative Stress Markers in Each Group	The extent of lipid peroxidation will be represented by plasma levels of malondialdehyde (MDA). Lower MDA levels suggest decreased oxidative damage. Simultaneously, the overall antioxidant activity in the plasma will be gauged through the ferric-reducing ability of plasma (FRAP). Elevated FRAP values indicate a heightened ability to resist oxidative stress.	From baseline (16th week) up to delivery
Secondary	Evaluation of Matrix Metalloproteinases and Inhibitors in Each Group	Serum concentrations of matrix metalloproteinases (MMPs) 2 and 9, as well as their inhibitors tissue inhibitor of metalloproteinases (TIMPs) 1 through 4, will be determined.	From baseline (16th week) up to delivery
Secondary	Evaluation of Diet Quality in Each Group Using the SISVAN Protocol	The quality of participants' diets will be assessed using a standardized SISVAN protocol. Concurrently, dietary recalls will be employed to provide a detailed account of participants' food consumption and nutritional patterns.	The SISVAN protocol will be employed at the enrollment.