The BEET-BP Trial - Investigating the Effect of Dietary Nitrates on Hypertension in Pregnancy

Pre-Eclampsia Clinical Trial

Official title:

The Effects of Dietary Nitrate Supplementation on Pregnancies Complicated by Chronic and New Onset Hypertension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04604535
• Other study ID #: 263871
• Status: Recruiting
• Phase: N/A
• Start date: October 22, 2020
• Est. completion date: December 30, 2022

Study information

• Verified date: October 2020
• Source: King's College Hospital NHS Trust
• Contact: Katherine Lau
• Phone: 07738247830
• Email: katherine.lau[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomised placebo controlled trial investigating the effects of dietary nitrate supplementation on hypertension in pregnancy

Description:

Reduced nitrate and nitrite concentrations have been found in women with preeclampsia (PE) and studies have shown increased concentrations of an endogenously generated Nitric Oxide Synthase inhibitor, amongst women with PE.

Nitrate and nitrite are required to produce Nitric Oxide (NO). NO is released from the endothelial lining of blood vessels, and acts to relax smooth muscle within the vasculature, acting as a potent vasodilator. Reduced NO concentrations are hence thought to contribute towards the systemic vascular constriction seen in PE.

Hypertensive diseases in pregnancy are an important cause of morbidity and mortality in both maternal, fetal and neonatal health. Treatment options are limited in pregnancy and hence alternative methods to improve blood pressure control should be sought.

In this randomised placebo controlled double blinded trial we aim to assess the effect of dietary nitrate supplementation on the hypertensive diseases of pregnancy and the subsequent maternal, fetal-neonatal outcomes. The safety and acceptability of dietary nitrate supplementation will also be confirmed in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: December 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged =18

• Able to give written informed consent

• Singleton pregnancies, between 24+0 to 36+6 weeks gestation with new onset gestational hypertension (defined by ISSHP2018 as new onset BP >140/90 and no evidence of proteinuria, biochemical or haematological abnormalities or fetal growth restriction) Or

• Singleton pregnancies, between 24+0 - 36+6 weeks gestation, with chronic hypertension (defined by ISSHP2018 as BP =140/90 predating the pregnancy or recognised at <20 week's gestation) Or

• Singleton pregnancies, between 24+0 - 36+6 weeks gestation, with preeclampsia (defined by ISSHP2018 as Gestational hypertension accompanied by = 1 of the following new onset conditions at or after 20 weeks' gestation:

• Proteinuria (24h urine collection>300mg/day, Protein-creatinine ratio>30 mg/mmol)

• Other markers of maternal organ dysfunction, including:

• Acute Kidney Injury (AKI) (creatinine =90µmol/L; 1mg/dL)

• Liver involvement (elevated transaminases e.g. alanine transaminase (ALT) or aspartate aminotransferase (AST) >40IU/L) with or without right upper quadrant or epigastric abdominal pain

• Neurological complications e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches and persistent visual scotomata

• Haematological complications (thrombocytopenia - platelet count <150 000/µL, disseminated intravascular coagulation, haemolysis

• Uteroplacental dysfunction (fetal growth restriction, abnormal umbilical artery doppler wave form analysis, or stillbirth)

Exclusion Criteria:

• Unable to tolerate taste of beetroot juice concentrate during taste test

• Multiple pregnancy

• History of acute or chronic liver conditions (aside from preeclampsia)

• Fetal aneuploidies or major fetal anomalies

• Unwillingness to comply with all study-related procedures e.g. Women who have used mouthwash or tongue scraping in last 7 days and are not able/unwilling unable to stop this for the duration of the study

• Women on treatment for gingivitis

• Women with persistent hyperemesis or ptyalism

• On Proton-pump-inhibitors/antacids other treatment for gastritis/peptic ulcer/gastric ulcers

• Those with long term antibiotic use e.g. prophylaxis of urinary tract infections (UTIs) or those who are likely to need repeated courses of antibiotics e.g. history of recurrent UTI

• Women with known allergy/intolerance to beetroot or lemon

• Type 1 and Type 2 diabetics

• Moderate iron deficiency anaemia with haemoglobin <100g/dL and/or ferritin <15µg/L

• Any blood disorder or significant illness that may affect platelet function and coagulation. However, patients taking low-dose aspirin (150mg) for preeclampsia prophylaxis who are at increased risk of developing preeclampsia will be included in the study.

• History of alcohol or recreational drug abuse use within the past 6 months

• Systemic autoimmune disease e.g. Rheumatoid Arthritis, antiphospholipid syndrome connective tissue disease e.g. Systemic Lupus Erythematous or other conditions known to be associated with chronic inflammation such as inflammatory bowel disease - Chron's disease/Ulcerative Colitis

• Women not intending to deliver at the recruiting site

• Participating in another intervention study that influences the outcomes of this study

• Those with serious mental illness or learning difficulties and unable to give written informed consent

• Those who are detained as a prisoner or detained in any secured unit, including those held under the Mental Health Act

• Those not fluent in local language, and absence of appropriate interpreter despite use of services such as Language Line

Related Conditions & MeSH terms

• Eclampsia
• Gestational Hypertension
• Hypertension
• Hypertension in Pregnancy
• Hypertension, Pregnancy-Induced
• Pre-Eclampsia
• Pregnancy Induced Hypertension

Intervention

Dietary Supplement:
• Concentrated beetroot juice
70mL concentrated beetroot juice (400mg nitrate)
• Placebo
70mL concentrated nitrate deplete beetroot juice (<0.01mmol/L nitrate)

Locations

Country	Name	City	State
United Kingdom	King's College Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
King's College Hospital NHS Trust	Barts and the London School of Medicine and Dentistry, Fetal Medicine Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gestational age of delivery secondary to preeclampsia		From recruitment until delivery
Secondary	Gestational age of delivery (due to any cause)		From recruitment until delivery
Secondary	Will beetroot juice supplementation increase or decrease the likelihood of maternal complications, including severe maternal complications		From recruitment until 8 weeks postnatal
Secondary	Will beetroot juice supplementation increase or decrease the likelihood of severe hypertension	Defined as = 160/110 mmHg	From recruitment until 8 weeks postnatal
Secondary	Will beetroot juice supplementation result in significant changes in systolic blood pressure and diastolic blood pressure		From recruitment until 8 weeks postnatal
Secondary	Will beetroot juice supplementation result in a significant change in the maximal number and dosages of antihypertensive medications required for blood pressure control		From recruitment until 8 weeks postnatal
Secondary	Will beetroot juice supplementation result in a significant change in maternal blood values and urinary protein excretion	Measured by creatinine, aspartate aminotransferase, alanine aminotransferase, uric acid, platelets, random urine protein creatinine ratio, protein concentration in a 24hour urine collection	From recruitment until 8 weeks postnatal
Secondary	Can the safety of beetroot juice supplementation in pregnancy be confirmed	Measurement of maternal methemoglobinaemia levels, maternal nitrosamine levels, maternal thyroid function, neonatal cord bloods, neonatal methemoglobinaemia levels	From recruitment until 8 weeks postnatal
Secondary	To confirm the acceptability of beetroot juice supplementation in pregnancy	A post-trial questionnaire	At 8 weeks postnatal