Testing a form of folate in pregnancy for women with high blood pressure
Clinical Antenatal Randomised Study to CharactErise Key Roles of TetrahydroFOLate in HyperTensive Pregnancies (CAREFOL-HT)
NA · University of Oxford · NCT05434195
This trial will test whether giving a biologically active folate (5‑MTHF) to pregnant women with pre-eclampsia or pregnancy-induced high blood pressure can raise a blood-vessel support molecule (BH4) and help mothers and babies.
Quick facts
| Phase | NA |
|---|---|
| Study type | Interventional |
| Enrollment | 128 (estimated) |
| Ages | 18 Years to 45 Years |
| Sex | Female |
| Sponsor | University of Oxford (other) |
| Locations | 2 sites (Oxford, Oxfordhsire and 1 other locations) |
| Trial ID | NCT05434195 on ClinicalTrials.gov |
What this trial studies
Women with pre-eclampsia or pregnancy-induced hypertension before 34 weeks who are receiving antenatal care at the John Radcliffe Hospital are randomly assigned to receive either Arcofolin® (5‑methyltetrahydrofolate) or placebo. The study measures levels of tetrahydrobiopterin (BH4) in maternal and placental tissues and monitors cardiovascular and pregnancy-related outcomes for mother and baby. The design compares biological markers and clinical outcomes between the two groups to see if the active folate restores BH4 and improves blood vessel function. Participants are followed through the antenatal period with safety monitoring and standard obstetric care.
Who should consider this trial
Good fit: Pregnant women aged 18–45 diagnosed with pre-eclampsia (or pregnancy-induced hypertension) before 34 weeks, able to give informed consent and receiving care at the John Radcliffe Hospital are ideal candidates.
Not a fit: People with chronic renal disease, low vitamin B12, current use of proton pump inhibitors or anti-epileptic drugs, known fetal trisomy or major fetal congenital anomalies are excluded and unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, the intervention could reduce complications from hypertensive pregnancies and lower long-term cardiovascular risk for mothers and their children.
How similar studies have performed: Preclinical studies in mice and experiments in human endothelial cells show 5‑MTHF can restore BH4 and reverse vascular changes, but clinical benefit in pregnant women has not yet been established.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria (Preeclampsia individuals): * Diagnosed with preeclampsia, as defined in Section 8.1, at \<34 weeks' gestation within the last 48 hours and with no delivery planned within the next week * Receiving antenatal care in the John Radcliffe Hospital * Participant is willing and able to give informed consent for participation in the study * Age \>18 and ≤45 years Exclusion Criteria (Preeclampsia individuals): The participant may not enter the study if ANY of the following apply: Maternal * History of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure or valve disease * History of preexisting chronic renal disease * Contraindication to taking folate related supplements * Folate supplementation in excess of 400mcg in the third trimester * Low vitamin B12 levels (\<148 pmol/L) * Intake of either proton pump inhibitors or anti-epileptic drugs * Organ dysfunction Fetal * Any known trisomy * Fetus with congenital heart defect * Fetus at a high risk of heart disease * Known infection of fetus * Known severe anaemia Inclusion Criteria (Normotensive individuals): * Participant is willing and able to give informed consent for participation in the study * Age \>18 and ≤45 years * Normotensive, blood pressures \<140/90 throughout antenatal period * Less than 2 moderate risk factors for hypertensive disease in pregnancy according to the NICE guideline for management of hypertension in pregnancy * SFlt/PIGF ratio \<35 Exclusion Criteria (Normotensive individuals): The participant may not enter the study if ANY of the following apply: Maternal * Diagnosis of hypertensive disorder of pregnancy * Use of beta blockers such as atenolol or equivalent * History of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure or valve disease * History of preexisting chronic renal disease Fetal * Any known trisomy * Fetus with congenital heart defect * Fetus at a high risk of heart disease * Known infection of fetus * Known severe anaemia
Where this trial is running
Oxford, Oxfordhsire and 1 other locations
- Oxford University Hospitals NHS Foundation Trust — Oxford, Oxfordhsire, United Kingdom (RECRUITING)
- Cardiovascular Clinical Research Facility — Oxford, Oxfordshire, United Kingdom (RECRUITING)
Study contacts
- Principal investigator: Paul Leeson, FRCP — University of Oxford, John Radcliffe Hospital
- Study coordinator: Annabelle Frost, MD
- Email: carefol-ht@cardiov.ox.ac.uk
- Phone: 01865 572833
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Pre-Eclampsia, Pregnancy Induced Hypertension, Pregnancy Related, 5-methyltetrahydrofolate, Tetrahydrobiopterin, Antenatal study