Acute Beetroot Juice Supplementation in Pre-eclampsia Pregnancies (BEET_PE)

Acute Effect of Beetroot Juice Supplementation in Pregnant Women With Pre-eclampsia: a Single-Blind Randomized Placebo-Controlled Trial

Pre-eclampsia is a serious condition that typically affects pregnant women after the 20th week of pregnancy, characterized by high blood pressure and damage to organs such as the kidneys and liver. Currently, treatment options are limited, which has prompted researchers to explore alternative approaches. One such promising alternative is dietary nitrate found in vegetables like beetroot, as nitrate can be converted into nitric oxide in the body, which helps lower blood pressure. This study aims to determine the acute effects of nitrate-rich beetroot juice on blood pressure, several blood and salivary markers in pregnant women with pre-eclampsia. Furthermore, the study will assess fetal blood flow using Doppler ultrasound. The investigators want to understand the kinetics of nitrate and nitric oxide metabolites and assess the temporal dependency of the hypotensive response. Through this investigation, the investigators seek evidence of nitrate-enriched beetroot juice as an adjunct therapy in managing pre-eclampsia.

Study Overview

• Status: Not yet recruiting
• Conditions: Pre-Eclampsia
• Intervention / Treatment: Dietary supplement: Beetroot juice; Dietary supplement: Placebo juice

Detailed Description

The study will include women diagnosed with either early-onset pre-eclampsia or late-onset pre-eclampsia, following the guidelines of the American College of Obstetricians and Gynecologists. Participants will be required to sign informed consent forms following a thorough explanation of the study. A total of four groups will be established, with twenty-four pregnant women randomly assigned to each group using a free online program. In each group (early-onset and late-onset pre-eclampsia), forty-eight pregnant women will receive nitrate-enriched beetroot juice (Beet It®, James White, UK), while another forty-eight will receive an equivalent amount of placebo juice. The trial will commence in the morning, between 7:30 and 8:30 am, after a standardized, low-nitrate breakfast provided by the hospital. Participants will be instructed to avoid nitrate-rich foods the previous evening and will receive guidance from the project team and the hospital's nutrition service. The hospital's nutritional team will oversee the dietary procedures. Ambulatory blood pressure monitoring will be conducted for six hours following the ingestion of juice or placebo. Saliva samples will be collected to assess nitrate reductase activity, and blood samples will be drawn to measure nitrate, nitrite, and nitrosothiol (nitric oxide metabolites), as well as to perform biochemical analyses of oxidative stress. Doppler ultrasound and Doppler velocimetry evaluation will be conducted at the peak action time of nitrate, which is estimated to occur two hours post-ingestion, based on previous research.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Priscila O Barbosa, Dr; Phone Number: +55166021000; Email: barbosapo@usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women at or beyond the 20th week of gestation.
• Hospitalized at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto.
• Diagnosed with early or late-onset pre-eclampsia confirmed by a medical professional.
• Capacity to provide written informed consent for study participation.

Exclusion Criteria:

• Multiple pregnancies.
• Uncontrolled arterial hypertension (Systolic Blood Pressure > 160 mmHg or Diastolic Blood Pressure > 100 mmHg).
• Pregnant women with a body mass index > 40 kg/m²
• Severe gestational complications.
• History of food allergy with hypersensitivity to beetroot.
• Smokers.
• Chronic alcohol consumption.
• Use of medications, except for antihypertensive.
• Diagnosis of renal or hepatic disease affecting nitrate metabolism.
• Cardiac conditions such as moderate to severe congestive heart failure and coronary artery disease.
• Pre-existing type 1 or type 2 diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early-onset pre-eclampsia beetroot juice; A single dose of 70 ml of nitrate-rich beetroot juice containing 400 mg of nitrate.	Dietary supplement: Beetroot juice; In the morning, pregnant women with pre-eclampsia will consume a single dose of 70 ml of nitrate-rich beetroot juice containing 400 mg of nitrate. Participants will be monitored to assess the acute effects of nitrate intake for 6 hours.
Placebo Comparator: Early-onset pre-eclampsia placebo juice; A single dose of 70 ml of a formulation with a similar taste, smell, and texture.	Dietary supplement: Placebo juice; In the morning, pregnant women with pre-eclampsia will consume 70 ml of a placebo juice. The placebo juice will be similar in appearance and taste to the nitrate-rich beetroot juice. Participants will be monitored to compare the acute effects of beetroot juice with the placebo intake for 6 hours.
Experimental: Late-onset pre-eclampsia beetroot juice; A single dose of 70 ml of nitrate-rich beetroot juice containing 400 mg of nitrate.	Dietary supplement: Beetroot juice; In the morning, pregnant women with pre-eclampsia will consume a single dose of 70 ml of nitrate-rich beetroot juice containing 400 mg of nitrate. Participants will be monitored to assess the acute effects of nitrate intake for 6 hours.
Placebo Comparator: Late-onset pre-eclampsia placebo juice; A single dose of 70 ml of a formulation with a similar taste, smell, and texture.	Dietary supplement: Placebo juice; In the morning, pregnant women with pre-eclampsia will consume 70 ml of a placebo juice. The placebo juice will be similar in appearance and taste to the nitrate-rich beetroot juice. Participants will be monitored to compare the acute effects of beetroot juice with the placebo intake for 6 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Effect of Beetroot Juice Supplementation on Blood Pressure	Assessment of the acute effect of beetroot juice supplementation on blood pressure (measured in millimetres of mercury - mmHg) in pregnant women diagnosed with early and late-onset pre-eclampsia, measured every 30 minutes up to 6 hours post-supplementation, starting 30 minutes before ingestion, compared to a placebo group.	Every 30 minutes up to 6 hours post-supplementation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Nitric Oxide Metabolites	Assessment of plasma concentrations of nitric oxide metabolites (nitrite, nitrate and nitrosothiol) in pregnant women diagnosed with pre-eclampsia, comparing those receiving beetroot juice supplementation and those receiving placebo.	At baseline and up to 6 hours post-supplementation.
Concentration of Salivary Nitrate Reductase Enzyme	Assessment of the activity of the nitrate reductase enzyme in saliva in each study group.	At baseline and up to 6 hours post-supplementation.
Plasma Lipid Peroxidation Levels	Assessment of the degree of lipid peroxidation, measured by the level of malondialdehyde in each study group.	At baseline and up to 6 hours post-supplementation.
Concentration of Total Antioxidant Capacity in Plasma	Determination of the plasma concentration of total antioxidant capacity of plasma, measured in Trolox equivalent antioxidant capacity, in each study group.	At baseline and up to 6 hours post-supplementation.
Maternal Blood Flow Velocity	Maternal blood flow velocity will be measured in centimeters per second (cm/s) using Doppler ultrasound, in each study group.	2 hours post-supplementation of beetroot juice or placebo.
Fetal Heart Rate	Fetal heart rate will be measured in beats per minute (bpm) using Doppler ultrasound, in each study group.	2 hours post-supplementation of beetroot juice or placebo.
Umbilical Arterial Pulsatility Index	The umbilical arterial pulsatility index will be calculated and reported as a percentile, in each group.	2 hours post-supplementation of beetroot juice or placebo.

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Universidade Estadual Paulista Júlio de Mesquita Filho; Hospital das Clínicas de Ribeirão Preto
• Investigators: Principal Investigator: Ricardo C Cavalli, Dr, Medical School of Ribeirao Preto, USP

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Nitric Oxide; Pre-eclampsia; Beetroot Juice
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: 2024/823

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will provide access to individual de-identified participant data and related study documents upon request from qualified researchers, subject to certain criteria, conditions, and exceptions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No