RecruitingNAINTERVENTIONAL

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

This study investigates why some women develop high blood pressure during pregnancy, which can lead to complications like premature birth. It focuses on a molecule called BH4, important for healthy blood vessels, which might be at lower levels in mothers with high blood pressure in pregnancy. Researchers want to see if changing BH4 levels with a specific folate supplement (Arcofolin® 5-Methyltetrahydrofolate) can improve blood vessel function. The study will compare BH4 levels and heart/blood vessel health in pregnant women with high blood pressure to those with normal blood pressure, and within the high blood pressure group, between those taking the supplement and a dummy pill. This could help us understand how to reduce risks for mothers and babies.

At a glance

Status

Recruiting

Phase

Sponsor

University of Oxford

Enrolment target

128

Start

01 Jun 2021

Estimated completion

01 Oct 2026

Pre-Eclampsia Pregnancy Induced Hypertension Pregnancy Related

What is this study about?

High blood pressure during pregnancy is a common problem that can affect both mothers and their babies. It can lead to early births and babies being smaller than expected. We also know that mothers who experience high blood pressure in pregnancy, and their children, might have a higher chance of developing high blood pressure and heart problems later in life. Previous research has shown that high blood pressure in pregnancy can cause changes to the heart and blood vessels in both mothers and babies, which might explain these long-term risks.

Our team has been looking into a molecule called tetrahydrobiopterin (or BH4), which is really important for keeping blood vessels healthy. We've found that mothers with high blood pressure during pregnancy tend to have lower levels of BH4 in their placenta and the umbilical cord. This suggests that BH4 might play a key role in this condition. We want to understand how closely BH4 levels are linked to the features of high blood pressure in pregnancy, and if giving a special nutritional supplement could help improve how blood vessels work.

In this study, called CAREFOL-HT, we're comparing BH4 levels between pregnant women with high blood pressure and those with normal blood pressure. We'll also use ultrasound scans, like heart scans (echocardiography) and scans of the baby (fetal sonography), to see how the heart and blood vessels look and function in these different groups. Part of the study will involve giving some women with high blood pressure either a folate supplement (Arcofolin® 5-Methyltetrahydrofolate) or a dummy pill (placebo) to see if the supplement can boost BH4 levels and improve blood vessel health.

Key takeaways

Investigating high blood pressure in pregnancy and long-term health risks.
Focuses on a molecule called BH4 important for blood vessels.
Testing if a specific folate supplement improves blood vessel health.
Involves blood tests and ultrasound scans for heart and baby.
Compares women with high blood pressure to those with normal blood pressure.

Who may be eligible?

The study aims to include pregnant women between 18 and 45 years old. Women with a recent diagnosis of high blood pressure in pregnancy (pre-eclampsia) before 34 weeks of pregnancy, who are receiving care at John Radcliffe Hospital, may be able to join one group of the study.

Another group of the study will include pregnant women with normal blood pressure, also aged 18 to 45. They should have consistently normal blood pressure throughout their pregnancy and only a few or no risk factors for developing high blood pressure in pregnancy.

However, there are reasons why you might not be able to join. These include certain heart or kidney conditions, if you're taking specific medications (like some for epilepsy or stomach acid), or if your baby has certain known health issues. You also won't be able to join if you're already taking high doses of folate supplements or if you have very low vitamin B12 levels. The research team will review your full medical history to confirm if you're suitable.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you a woman aged between 18 and 45 years old?
Are you currently pregnant?
Do you have a recent diagnosis of high blood pressure in pregnancy (pre-eclampsia) OR consistently normal blood pressure?
Are you receiving antenatal care at John Radcliffe Hospital?
Do you have any existing heart or kidney conditions (this might exclude you)?
Are you taking specific medications that might affect participation (e.g., proton pump inhibitors, some anti-epileptic drugs)?

Answer every question to see your result.

What does participation involve?

If you decide to take part, you'll be assigned to either receive the active folate supplement (Arcofolin® 5-Methyltetrahydrofolate) or a dummy pill (placebo). This is decided randomly, like flipping a coin. You'll have several study visits where we'll take blood samples to measure BH4 and other molecules, and you'll have ultrasound scans of your heart, blood vessels, and your baby. These scans are similar to those you might have during regular pregnancy care. We'll also ask questions about your health and monitor your blood pressure. The total duration of your involvement will depend on when you join the study and how your pregnancy progresses, typically lasting until after your baby is born, with follow-up assessments.

Potential risks and benefits

Participating in this study might provide valuable information that could help improve care for future pregnant women with high blood pressure. While there's no direct guarantee of personal benefit, you will receive close medical monitoring throughout the study. The folate supplement being tested is approved for use in pregnancy and is generally considered safe, but like all medications, there's always a minor chance of unexpected side effects. We will inform you of any known potential risks during the consent process. You are free to withdraw from the study at any time, for any reason, without affecting your usual medical care.

Locations (2)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Oxford University Hospitals NHS Foundation Trust
Verified postcode
Oxford, United Kingdom· Recruiting
Cardiovascular Clinical Research Facility
Verified postcode
Oxford, United Kingdom· Recruiting

Common questions

What is high blood pressure in pregnancy?

It's when a pregnant woman develops high blood pressure, sometimes with other symptoms like protein in the urine, that can affect the mother and baby. It's also known as pre-eclampsia or pregnancy-induced hypertension.

What is BH4 and why is it important?

BH4 is a natural molecule in the body that helps keep your blood vessels healthy and working properly. We think lower levels of BH4 might be linked to high blood pressure in pregnancy.

Is the supplement safe?

Yes, the specific folate supplement (Arcofolin® 5-Methyltetrahydrofolate) is a form of folate that is safe and approved for use during pregnancy, similar to the folic acid many women take.

Will I know if I'm getting the active supplement or the dummy pill?

No, this is a 'blinded' study. To make sure the results are fair, neither you nor the study team will know whether you are receiving the active supplement or the dummy pill until the study is over.

What happens if I change my mind about participating?

You are free to leave the study at any time, for any reason, without needing to give an explanation. Your decision won't affect the medical care you receive.

How to find out more

Annabelle Frost, MD

carefol-ht@cardiov.ox.ac.uk 01865 572833 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.