Clinical Antenatal Randomised Study to CharactErise Key Roles of TetrahydroFOLate in HyperTensive Pregnancies

Summary

Study background

High blood pressure during pregnancy is a worldwide health problem that can be dangerous to mothers and commonly causes premature birth and small babies. There is also growing evidence that mothers who suffer from high blood pressure in pregnancy, and their babies, have a higher risk of high blood pressure and cardiovascular disease later in life. Previous studies have revealed detrimental changes in the structure and function of the heart and blood vessels of mothers, and their babies, who experience this common complication. These changes may explain their increased risk of later disease. The investigators have also learned through previous studies that tetrahydrobiopterin (BH4), a molecule that has a role in blood vessel health, plays an important role in stabilising blood vessel function. Lower levels of BH4 are evident in both the placenta and the umbilical cord from mothers with high blood pressure. We, therefore, want to investigate how closely BH4 levels are related to clinical features of pre-eclampsia and whether altering levels of BH4, using a nutritional supplement, improves features of the disease such as blood vessel function. To do this, the investigators need to compare the levels of BH4 between mothers with pre-eclampsia, those taking the supplement and those without pre-eclampsia. The investigators also compare how the heart and blood vessels look and function in these groups using ultrasound methods, including echocardiography and fetal sonography.

Study objectives

CAREFOL-HT will assess how levels of BH4 differ in pregnant women with high blood pressure and if this is reflected in functional changes in the heart and blood vessels of these women. The investigators will also determine whether changing levels of BH4, using a tetrahydrofolate supplement (5-MTHF), changes blood vessel function.

Conditions

• Pre-Eclampsia
• Pregnancy Induced Hypertension
• Pregnancy Related

Interventions

DIETARY_SUPPLEMENT

Arcofolin® 5-Methyltetrahydrofolate

5-methyltetrahydrofolate (5-MTHF) is the biologically active form of reduced folate, which can increase BH4 availability. 5-MTHF is available as a nutritional vitamin (Merck \& Cie) for human use including during pregnancy. Two out of three preeclamptic study groups will receive 5-MTHF - one at a low dose and the other at a high dose.

DIETARY_SUPPLEMENT

Arcofolin® Placebo

The placebo, this consists of the same excipients as 5-MTHF, microcrystalline cellulose and silica with no active ingredient.

Sponsors & Collaborators

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• British Heart Foundation

  collaborator OTHER

• Merck & Cie

  collaborator UNKNOWN

• University of Oxford

  lead OTHER

Principal Investigators

• Paul Leeson, FRCP · University of Oxford, John Radcliffe Hospital

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-06-01

Primary Completion

2026-01-01

Completion

2026-10-31

Countries

• United Kingdom

Study Locations