Pre-EclampsiaCAREFOL-HTNCT05434195
Clinical Antenatal Randomised Study to CharactErise Key Roles of TetrahydroFOLate in HyperTensive Pregnancies
A study testing Arcofolin® 5-Methyltetrahydrofolate in people with Pre-Eclampsia and Pregnancy Induced Hypertension, run by University of Oxford at 2 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pre-Eclampsia, Pregnancy Induced Hypertension, Pregnancy Related
- What is being tested?
- Arcofolin® 5-Methyltetrahydrofolate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Jun 2021to Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Participant is willing and able to give informed consent for participation in the study
- Age >18 and ≤45 years
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford, Oxfordhsire, OX3 9DU
Yvonne Kenworthy
- Recruiting
Cardiovascular Clinical Research Facility
Oxford, Oxfordshire, OX3 7RD
Yvonne Kenworthy, yvonne.kenworthy@cardiov.ox.ac.uk
About this study
Official title: Clinical Antenatal Randomised Study to CharactErise Key Roles of TetrahydroFOLate in HyperTensive Pregnancies (CAREFOL-HT)
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.
Read more
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.
Read the detailed description
High blood pressure during pregnancy is a world-wide 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 both have a higher risk of high blood pressure and cardiovascular disease in later 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 which may be important in understanding the subsequent increased risk of later disease. The investigators have also learned through previous work carried out by our research group that certain biological processes may be disturbed in women with high blood pressure in pregnancy. One of these processes involves a molecule called tetrahydrobiopterin (also known as BH4) which is required for the correct functioning of blood vessels. Supplementation with biologically-active forms of reduced folate are able to increase the levels of this molecule and can reverse the changes caused by high blood pressure in pregnant mice, and in cultured human endothelial cells. These particular folate supplements are safe and approved for use in pregnancy, but are not widely used as they are more specialised and currently less available than folic acid, the oxidized form of folate that is widely used for supplementation in pregnancy. However, folic acid does not have the same effects as the specific biologically-active form of reduced folate (tetrahydrofolate), because folic acid requires enzymatic conversion within the body in order to generate the biologically-active form of reduced folate. Whilst the use of folic acid appears to be sufficient in most cases to increase folate levels in the prevention of fetal abnormalities such as neural tube defects, the conversion of folic acid to its biologically-active reduced form may be itself deficient or detrimental in women with preeclampsia, and does not increase tetrahydrobiopterin levels. Indeed, folic acid treatment has been found to be ineffective in a large clinical trial to improve high blood pressure in pregnancy women.
This clinical trial will investigate the levels of biologically-active forms of reduced folates. As a way to increase the levels of tetrahydrobiopterin, in pregnant women with high blood pressure, women participating in the trial will take either a low dose or a high dose of a biologically-active form of reduced folate (tetrahydrofolate supplement) until delivery of their baby. A further group of women with high blood pressure will be recruited and will take a placebo. Blood tests will be taken and measurements performed to evaluate the heart and blood vessels of the participating women and their babies upon entry into the study and again at the time of birth. The investigators will also collect the umbilical cord and placenta tissue samples once the baby has been born, so that the investigators can assess blood vessel cell function following tetrahydrofolate supplementation in laboratory studies. In addition to the groups of women with high blood pressure, the investigators will also invite a group of women with an uncomplicated pregnancy to take part, as a comparison group, these women will not receive any supplementation. The investigators aim to investigate how levels of factors in the folate pathway 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 also aim to study whether this tetrahydrofolate supplement can increase the levels of tetrahydrobiopterin and if this improves blood vessel function. If successful, the investigators hope that the results of this study will enable us to design and conduct a larger study in future in order to test whether taking this tetrahydrofolate supplement will stop or reverse the changes caused by high blood pressure in pregnancy.
- Being tested
- Arcofolin® 5-Methyltetrahydrofolate, Arcofolin® Placebo
- Keywords
- 5-methyltetrahydrofolate, Tetrahydrobiopterin, Pre-Eclampsia, Antenatal study
- Medical subject headings
- Pre-Eclampsia, Hypertension, Pregnancy-Induced
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arcofolin® 5-MethyltetrahydrofolateDietary supplement
Also called Arcofolin®
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.
Arcofolin® PlaceboDietary supplement
The placebo, this consists of the same excipients as 5-MTHF, microcrystalline cellulose and silica with no active ingredient.
| Study group | Role | What they receive |
|---|---|---|
| Normotensive | No intervention | A sub-cohort of 32 normotensive women will be recruited to establish normal pregnancy values for the measures performed as well as validation of outcome measures. |
| Preeclampsia - Placebo | Placebo comparator | A sub-cohort of 32 preeclampsia women will be recruited taking the placebo. Receives: Dietary Supplement: Arcofolin® Placebo |
| Preeclampsia - low dosage | Active comparator | A sub-cohort of 32 preeclampsia women will be recruited taking the placebo low dose of 5-MTHF. Receives: Dietary Supplement: Arcofolin® 5-Methyltetrahydrofolate |
| Preeclampsia - high dosage | Active comparator | A sub-cohort of 32 preeclampsia women will be recruited taking the placebo high dose of 5-MTHF. Receives: Dietary Supplement: Arcofolin® 5-Methyltetrahydrofolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the change of maternal circulating BH4 biomarkers levels at baseline to prior to delivery.
Levels of BH4, Dihydrobiopterin (BH2), tetrahydrofolate, dihydrofolate reductase (DHFR), GTP cyclohydrolase I (GTPCH) will be assessed.
Measured: Baseline (gestation approx. 28- 34 weeks) and prior to delivery
To assess the change of maternal nitric oxide levels at baseline to prior to delivery.
Levels of nitric oxide will be assessed in maternal serum samples.
Measured: Baseline (gestation approx. 28- 34 weeks) and prior to delivery
To assess the levels of BH4 biomarkers in umbilical cord blood.
Levels of BH4, Dihydrobiopterin (BH2), tetrahydrofolate, dihydrofolate reductase (DHFR), GTP cyclohydrolase I (GTPCH) will be assessed in cord blood serum.
Measured: At delivery
To assess the levels of BH4 biomarkers in placenta.
Levels of BH4, Dihydrobiopterin (BH2), tetrahydrofolate, dihydrofolate reductase (DHFR), GTP cyclohydrolase I (GTPCH) will be assessed in placental tissues.
Measured: At delivery
To assess the levels of nitric oxide levels in umbilical cord blood.
Levels of nitric oxide will be assessed in cord blood serum.
Measured: At delivery
To assess the levels of nitric oxide levels in placenta.
Levels of nitric oxide will be assessed in placental tissues.
Measured: At delivery
Secondary outcomes (8)
To assess whether maternal BH4 biomarkers levels are correlated with changes in the offspring.
Levels of folates, BH4 BH2, tetrahydrofolate, DHFR, and GTPCH will be assessed
Measured: Maternal: at baseline (gestation approx. 28- 34 weeks) and prior to delivery Umbilical cord and placenta: immediately after delivery
To assess whether BH4 biomarkers levels are correlated with improved angiogenesis profile of maternal blood-derived endothelial cell forming colonies (ECFCs). changes in in-vitro maternal and fetal vascular function.
Angiogenesis profile of ECFCs (tube length, diameter, total area and duration for regression) will be determined via in vitro tube formation assay.
Measured: At baseline (gestation approx. 28- 34 weeks) and prior to delivery
To assess whether BH4 biomarkers levels are correlated with improved angiogenesis profile of human umbilical vein endothelial cells (HUVECs).
Angiogenesis profile of HUVECs (tube length, diameter, total area and duration for regression) will be determined via in vitro tube formation assay.
Measured: At delivery
To assess whether BH4 biomarkers levels are correlated with circulating angiogenic molecules (soluble fms-like tyrosine kinase-1 and placental growth factor).
Measurement of sFlt-1 and PlGF will be measure in serum samples in the clinical biochemistry laboratory.
Measured: At baseline (gestation approx. 34 weeks) and prior to delivery.
To assess whether BH4 biomarkers levels are correlated with in-vivo flow-mediated dilatation (FMD) changes.
Brachial artery FMD induced by reactive hyperemia to assess vascular endothelial function.
Measured: At baseline (gestation approx. 34 weeks) and prior to delivery.
To assess whether BH4 biomarkers levels are correlated with peripheral blood pressure changes.
Flow mediated dilatation, peripheral blood pressure, left and right ventricular mass and volumes and cardiac diastolic function.
Measured: At baseline (gestation approx. 34 weeks) and prior to delivery.
To assess whether tetrahydrofolate levels are associated with cardiac remodelling.
Echocardiography will be performed and left and right ventricular mass and volumes and cardiac diastolic function will be investigated.
Measured: At baseline (gestation approx. 34 weeks) and prior to delivery.
To investigate the acceptability and feasibility of taking the supplementation during pregnancy via questionnaire.
All participants will also be asked to complete a questionnaire assessing the acceptability of 5-MTHF supplementation. This questionnaire can be completed at any point before discharge.
Measured: After delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2022
- Study start1 Jun 2021
- Primary completion1 Jan 2026
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, British Heart Foundation, Merck & Cie
- Responsible party
- Sponsor
- Investigators
- Paul Leeson, FRCP, Principal investigator, University of Oxford, John Radcliffe Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05434195
- Sponsor's protocol ID
- 295830
- Acronym
- CAREFOL-HT
- Status last verified
- Apr 2026
- First submitted
- 5 May 2022
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cutler HR, Hanssen H, Hauser C, Streese L, Sattwika PD, Kitt J, McCourt A, Suriano K, Kenworthy Y, Frost A, Krasner S, Lewandowski AJ, Lapidaire W, Leeson P. Retinal Vascular Caliber: 6 to 12 Months and 15 to 25 Years Following Hypertensive Pregnancy. Hypertension. 2026 Aug;83(8):e27171. doi: 10.1161/HYPERTENSIONAHA.126.27171. Epub 2026 Jun 17.
PubMed 42305089Cutler HR, Kitt J, Sattwika PD, Finnigan LEM, Estevez-Fernandez A, Kenworthy Y, Suriano K, Frost A, Krasner S, Johnson C, McCourt A, Mills R, Tucker K, Cairns A, Roman C, Aye C, Mackillop L, Thilaganathan B, Chappell LC, Raman B, Lewandowski AJ, Lapidaire W, Leeson P. Subclinical Postpartum Renal Structure After Hypertensive Pregnancy Disorders. Hypertension. 2025 Nov;82(11):1948-1958. doi: 10.1161/HYPERTENSIONAHA.125.25130. Epub 2025 Aug 31.
PubMed 40886083
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Antenatal Randomised Study to CharactErise Key Roles of TetrahydroFOLate in HyperTensive Pregnancies (CAREFOL-HT)
- ClinicalTrials.gov ID
- NCT05434195
- Acronym / sponsor ID
- CAREFOL-HT / 295830
- Keywords
- 5-methyltetrahydrofolate, Tetrahydrobiopterin, Pre-Eclampsia, Antenatal study
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 128 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, British Heart Foundation, Merck & Cie
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 1 Jan 2026 (actual)
- Study completion
- Oct 2026 (estimated)
- First posted
- 27 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
High blood pressure during pregnancy is a world-wide 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 both have a higher risk of high blood pressure and cardiovascular disease in later 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 which may be important in understanding the subsequent increased risk of later disease. The investigators have also learned through previous work carried out by our research group that certain biological processes may be disturbed in women with high blood pressure in pregnancy. One of these processes involves a molecule called tetrahydrobiopterin (also known as BH4) which is required for the correct functioning of blood vessels. Supplementation with biologically-active forms of reduced folate are able to increase the levels of this molecule and can reverse the changes caused by high blood pressure in pregnant mice, and in cultured human endothelial cells. These particular folate supplements are safe and approved for use in pregnancy, but are not widely used as they are more specialised and currently less available than folic acid, the oxidized form of folate that is widely used for supplementation in pregnancy. However, folic acid does not have the same effects as the specific biologically-active form of reduced folate (tetrahydrofolate), because folic acid requires enzymatic conversion within the body in order to generate the biologically-active form of reduced folate. Whilst the use of folic acid appears to be sufficient in most cases to increase folate levels in the prevention of fetal abnormalities such as neural tube defects, the conversion of folic acid to its biologically-active reduced form may be itself deficient or detrimental in women with preeclampsia, and does not increase tetrahydrobiopterin levels. Indeed, folic acid treatment has been found to be ineffective in a large clinical trial to improve high blood pressure in pregnancy women.
This clinical trial will investigate the levels of biologically-active forms of reduced folates. As a way to increase the levels of tetrahydrobiopterin, in pregnant women with high blood pressure, women participating in the trial will take either a low dose or a high dose of a biologically-active form of reduced folate (tetrahydrofolate supplement) until delivery of their baby. A further group of women with high blood pressure will be recruited and will take a placebo. Blood tests will be taken and measurements performed to evaluate the heart and blood vessels of the participating women and their babies upon entry into the study and again at the time of birth. The investigators will also collect the umbilical cord and placenta tissue samples once the baby has been born, so that the investigators can assess blood vessel cell function following tetrahydrofolate supplementation in laboratory studies. In addition to the groups of women with high blood pressure, the investigators will also invite a group of women with an uncomplicated pregnancy to take part, as a comparison group, these women will not receive any supplementation. The investigators aim to investigate how levels of factors in the folate pathway 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 also aim to study whether this tetrahydrofolate supplement can increase the levels of tetrahydrobiopterin and if this improves blood vessel function. If successful, the investigators hope that the results of this study will enable us to design and conduct a larger study in future in order to test whether taking this tetrahydrofolate supplement will stop or reverse the changes caused by high blood pressure in pregnancy.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normotensive | No intervention | –A sub-cohort of 32 normotensive women will be recruited to establish normal pregnancy values for the measures performed as well as validation of outcome measures. |
| Preeclampsia - Placebo | Placebo comparator | Dietary Supplement: Arcofolin® PlaceboA sub-cohort of 32 preeclampsia women will be recruited taking the placebo. |
| Preeclampsia - low dosage | Active comparator | Dietary Supplement: Arcofolin® 5-MethyltetrahydrofolateA sub-cohort of 32 preeclampsia women will be recruited taking the placebo low dose of 5-MTHF. |
| Preeclampsia - high dosage | Active comparator | Dietary Supplement: Arcofolin® 5-MethyltetrahydrofolateA sub-cohort of 32 preeclampsia women will be recruited taking the placebo high dose of 5-MTHF. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
- Participant is willing and able to give informed consent for participation in the study
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arcofolin® 5-MethyltetrahydrofolateAlso: Arcofolin®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 | Preeclampsia - high dosage, Preeclampsia - low dosage |
| Arcofolin® PlaceboThe placebo, this consists of the same excipients as 5-MTHF, microcrystalline cellulose and silica with no active ingredient. | Dietary supplement | Preeclampsia - Placebo |
Primary outcome
To assess the change of maternal circulating BH4 biomarkers levels at baseline to prior to delivery.
Time frame: Baseline (gestation approx. 28- 34 weeks) and prior to delivery
Levels of BH4, Dihydrobiopterin (BH2), tetrahydrofolate, dihydrofolate reductase (DHFR), GTP cyclohydrolase I (GTPCH) will be assessed.
To assess the change of maternal nitric oxide levels at baseline to prior to delivery.
Time frame: Baseline (gestation approx. 28- 34 weeks) and prior to delivery
Levels of nitric oxide will be assessed in maternal serum samples.
To assess the levels of BH4 biomarkers in umbilical cord blood.
Time frame: At delivery
Levels of BH4, Dihydrobiopterin (BH2), tetrahydrofolate, dihydrofolate reductase (DHFR), GTP cyclohydrolase I (GTPCH) will be assessed in cord blood serum.
To assess the levels of BH4 biomarkers in placenta.
Time frame: At delivery
Levels of BH4, Dihydrobiopterin (BH2), tetrahydrofolate, dihydrofolate reductase (DHFR), GTP cyclohydrolase I (GTPCH) will be assessed in placental tissues.
To assess the levels of nitric oxide levels in umbilical cord blood.
Time frame: At delivery
Levels of nitric oxide will be assessed in cord blood serum.
To assess the levels of nitric oxide levels in placenta.
Time frame: At delivery
Levels of nitric oxide will be assessed in placental tissues.
8 secondary outcomes
To assess whether maternal BH4 biomarkers levels are correlated with changes in the offspring.
Time frame: Maternal: at baseline (gestation approx. 28- 34 weeks) and prior to delivery Umbilical cord and placenta: immediately after delivery
To assess whether BH4 biomarkers levels are correlated with improved angiogenesis profile of maternal blood-derived endothelial cell forming colonies (ECFCs). changes in in-vitro maternal and fetal vascular function.
Time frame: At baseline (gestation approx. 28- 34 weeks) and prior to delivery
To assess whether BH4 biomarkers levels are correlated with improved angiogenesis profile of human umbilical vein endothelial cells (HUVECs).
Time frame: At delivery
To assess whether BH4 biomarkers levels are correlated with circulating angiogenic molecules (soluble fms-like tyrosine kinase-1 and placental growth factor).
Time frame: At baseline (gestation approx. 34 weeks) and prior to delivery.
To assess whether BH4 biomarkers levels are correlated with in-vivo flow-mediated dilatation (FMD) changes.
Time frame: At baseline (gestation approx. 34 weeks) and prior to delivery.
To assess whether BH4 biomarkers levels are correlated with peripheral blood pressure changes.
Time frame: At baseline (gestation approx. 34 weeks) and prior to delivery.
To assess whether tetrahydrofolate levels are associated with cardiac remodelling.
Time frame: At baseline (gestation approx. 34 weeks) and prior to delivery.
To investigate the acceptability and feasibility of taking the supplementation during pregnancy via questionnaire.
Time frame: After delivery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Derived from this study: PubMed 42305089Cutler HR, Hanssen H, Hauser C, Streese L, Sattwika PD, Kitt J, McCourt A, Suriano K, Kenworthy Y, Frost A, Krasner S, Lewandowski AJ, Lapidaire W, Leeson P. Retinal Vascular Caliber: 6 to 12 Months and 15 to 25 Years Following Hypertensive Pregnancy. Hypertension. 2026 Aug;83(8):e27171. doi: 10.1161/HYPERTENSIONAHA.126.27171. Epub 2026 Jun 17.
- Derived from this study: PubMed 40886083Cutler HR, Kitt J, Sattwika PD, Finnigan LEM, Estevez-Fernandez A, Kenworthy Y, Suriano K, Frost A, Krasner S, Johnson C, McCourt A, Mills R, Tucker K, Cairns A, Roman C, Aye C, Mackillop L, Thilaganathan B, Chappell LC, Raman B, Lewandowski AJ, Lapidaire W, Leeson P. Subclinical Postpartum Renal Structure After Hypertensive Pregnancy Disorders. Hypertension. 2025 Nov;82(11):1948-1958. doi: 10.1161/HYPERTENSIONAHA.125.25130. Epub 2025 Aug 31.
- CAREFOL-HT StudyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Leeson, FRCP principal investigator
University of Oxford, John Radcliffe Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arcofolin® 5-Methyltetrahydrofolate in people with Pre-Eclampsia and Pregnancy Induced Hypertension, run by University of Oxford at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Annabelle Frost, MD (01865 572833 ext. 02833, carefol-ht@cardiov.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the change of maternal circulating BH4 biomarkers levels at baseline to prior to delivery. (time frame: Baseline (gestation approx. 28- 34 weeks) and prior to delivery). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05434195, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.