Clinical Research Directory

Placental Biology in Health and Disease

Pre-eclampsia (PET) is a condition characterised by high blood pressure and damage to other organs, and is a leading cause of maternal and fetal complications such as fetal growth restriction (FGR). Gestational diabetes mellitus (GDM) involves abnormal blood sugar levels during pregnancy and can have both short and long-term impacts on the health of the mother and child. Both conditions are linked to placental dysfunction but the precise mechanisms behind these links remain unclear. A major focus of this study is on extracellular vesicles (EVs) which are tiny, bubble-like particles released by the placenta into the mother's and baby's bloodstreams. These EVs act as messengers, carrying proteins, lipids and genetic material that can influence how cells function, even in parts of the body far from the placenta. Notably, the number and content of these EVs change in conditions like PET and GDM, suggesting they may play a role in the development of these complications. This single-site, observational, laboratory study aims to investigate how these EVs contribute to maternal health and disease. To enable analysis across different physiological and pathological conditions pregnant participants with healthy pregnancies, pregnancies predisposed to PET and pregnancies complicated by GDM, FGR and PET will be recruited alongside healthy non-pregnant controls. Recruitment will be from the Oxford University Hospitals NHS Foundation Trust and the Nuffield Department of Women's and Reproductive Health, University of Oxford (who fund the research). Demographic and clinical data will be collected as well as blood, urine, breath, placenta, umbilical cord, umbilical cord blood, amniotic fluid and/or uterine vein blood samples. Through examining EV content and function, it is hoped a better understanding of their role in pregnancy complications will be gained, including their potential as non-invasive biomarkers for early detection and targeted treatments, improving outcomes for mothers and babies worldwide.

Usability Evaluation of Gen AI-based Nutrition Chatbot for Pregnant Women

Background: Pregnancy imposes significant physical demands, with complications like gestational diabetes (GDM) and pre-eclampsia posing serious risks. Nutrition is crucial for mitigation, but accessing reliable guidance remains challenging. This study evaluates the feasibility of an AI chatbot providing nutritional guidance for managing these conditions. Methods: In a quasi-experimental design, 100 pregnant women will self-select into either the intervention group (n=50, using an AI chatbot) or control group (n=50, receiving standard care). The primary outcome is usability measured by the System Usability Scale (SUS) at 12 weeks, with an expected mean difference of ≥13 points. Secondary outcomes include technology acceptance (Technology Acceptance Model), user engagement, information accuracy, and changes in dietary knowledge/behaviors. Quantitative data will be analyzed using intention-to-treat and t-tests. Semi-structured interviews with 20 participants will explore user experiences through thematic analysis. Expected Results: The AI chatbot is anticipated to demonstrate superior usability and high user acceptance (TAM \>5.0/7), with improvements in dietary knowledge and behavior. Qualitative findings will provide insights into benefits, barriers, and engagement factors. Conclusion: This study will establish an evidence base on AI chatbot feasibility and acceptance for prenatal nutrition, informing tool optimization and future large-scale trials.

Pharmacokinetic Study to Evaluate Safety and Tolerability of EG-101 in Healthy Female Volunteers as a Safety Lead-In for Dosing in Pregnant Women With Severe Pre-eclampsia

Preeclampsia is one of the leading causes of maternal and fetal death. It is a syndrome of pregnant women and is usually characterized by new onset of hypertension and proteinuria after 20 weeks of gestation. This disease is a multisystem disorder affects most maternal organs, predominantly the vascular, renal, hepatic, cerebral and coagulation systems. While hypertension is almost always a symptom of this disease, preeclampsia is not the same as essential hypertension. This is a single-center, randomized, open-label, 4 period, 3-way crossover, single dose fasted study to evaluate the safety, tolerability and pharmacokinetics of four ascending doses of the EG-101 IV injection in healthy volunteers. Twenty-four subjects in total, with eight subjects randomly assigned to one of three different sequences for variation of doses under fasted conditions. Dosing duration is approximately 4 weeks and followed by the follow-up for each subject.

Vitamin D for Preventing Recurrent Preeclampsia in Pregnant Women

The goal of this clinical trial is to find out whether giving vitamin D to pregnant women who had pre-eclampsia in a previous pregnancy helps prevent the condition from coming back. The main question it aims to answer is: Does vitamin D supplementation reduce the chance of pre-eclampsia recurring in pregnant women with a history of pre-eclampsia? To answer this question, pregnant women attending the antenatal clinic at the Department of Obstetrics and Gynaecology, Nishtar Hospital Multan will be invited to join the study. Participants will be randomly assigned to two equal groups: * Vitamin D group: will take 4,000 IU of oral vitamin D until 36 weeks of gestation. * Placebo group: will receive a pill identical in appearance, taste, and consistency but without vitamin D. While on the study medication, each woman will visit the clinic every two weeks. At each visit, her blood pressure will be measured, and if it is 140/90 mmHg or higher, a urine test will check for protein to identify pre-eclampsia as per hospital protocol. Any diagnosis of pre-eclampsia will lead to standard care, and the outcome will be recorded. At the end, researchers will compare how many women in each group developed recurrent pre-eclampsia. This study will help answer whether vitamin D supplementation can safely reduce the risk of pre-eclampsia returning in women with a prior history - a question important for improving pregnancy outcomes and maternal health.

PRIOR Study (Pre-eclampsia Risk In Oocyte Recipients)

The aim of this prospective observational cohort study is to investigate the pathophysiological mechanisms behind and risk of pre-eclampsia in women pregnant after fertility treatment with oocyte donation. The participants are included in of of two cohorts. One includes women pregnant after oocyte donation whereas the other includes women pregnant after IVF treatment with autologous oocytes. Participants will be followed throughout pregnancy with blood samples, blood pressure, clinical controls and ultrasound examinations. Clinical outcomes will be registered post-partum.

Oxford Luteal Dysfunction and Placental Insufficiency Study

High blood pressure (BP) affects approximately 1 in 10 pregnancies. About half of women with high blood pressure in pregnancy develop a serious complication called preeclampsia, which kills over 70,000 women and 500,000 babies every year worldwide. Despite its devastating impact, scientists know little about preeclampsia prevention or treatment. Research has shown that preeclampsia results mainly from an abnormal attachment of the placenta to the lining of the womb. In the first 8 weeks of pregnancy, placental attachment depends on the release of hormones (for example, progesterone) by a gland in the ovary called the corpus luteum. Low blood levels of progesterone in early pregnancy are associated with a reduced chance of having a live baby and higher risk of miscarriage. Giving progesterone to women at risk of miscarriage in early pregnancy reduces their chance of developing preeclampsia by nearly 40%. These results highlight the crucial role of the corpus luteum in normal pregnancy, but there is a need for high-quality studies to identify women whose corpus luteum may be defective. Giving these women medicines to treat corpus luteal defects may lead to normal attachment of the placenta, reducing the risk of pregnancy complications such as preeclampsia. The investigators propose a study that will investigate whether ultrasound features of the corpus luteum and blood and urine levels of corpus luteal hormones may predict preeclampsia.

Prevalence of Blood Pressure Complications During Cesarean Section in Pre-eclamptic Patients (HOPE)

Preeclampsia (PE) is an obstetric placental vascular pathology with a prevalence of 2 to 5% of pregnant women. It is defined by learned societies by the association of high blood pressure (BP≥140/90mmHg) and proteinuria \> 0.3g/day. The last French Maternal Mortality Report 2024 places cardiovascular complications among the main causes of maternal death. PE has an increasing number of deaths in 2016-2018 and significant preventability (66%). Cesarean sections in pre-eclamptic patients are difficult procedures and, do not benefit from any specific recommendations. Cesarean section is promptly performed under regional anesthesia by spinal anesthesia or spinal anesthesia with combined epidural, techniques that cause maternal arterial hypotension with consequences for the baby. These hypertensive patients, often on antihypertensives, challenge the anesthesiologist to manage the hemodynamic balance between the risk of arterial hypotension generated by the anesthesia corrected by vasoactive amines and the risk of major hypertension secondary to their management. The major risk in these patients with low platelet counts is hemorrhagic stroke. Our study is an observational, bi-centric study between the maternity wards of the Clermont Ferrand and Lille University Hospitals. It consists of collecting data prospectively on all pre-eclamptic patients undergoing a non-urgent cesarean section. The objective is to observe the management of hemodynamics and calculate the prevalence of complications such as maternal hypotension and/or hypertension through the implementation of non-invasive monitoring (ClearSight). Patients meeting the inclusion and non-inclusion criteria may be included in the study by an investigator after having given a non-opposition agreement after having received clear and fair information about the study. In any case, the care of patients participating in the study will not be modified in any way compared to the usual practices of the services.

LimPrOn: Limburg Pre-eclampsia Investigation

Background: Multiple adaptations at the cardiovascular system occurs during pregnancy. In the pregnancy condition pre-eclampsia (PE), this adaptations are abnormal. Five to eight percent of all pregnant women worldwide will develop PE. PE is a pregnancy condition which is characterized with a high blood pressure (\>140/90 mm Hg) and the occurrence of proteinuria (\>3g/dl/24h) after 20 weeks of gestation. When untreated, this condition can have severe complications for both mother and child. It's important to monitor women with a high risk for developing PE for an early detection and treatment of this condition. For this reason, a multicenter study is set up with the following applications: 1. NICCOMO and Maternal Venous Doppler Echography: impedance cardiograph and an echography of the heart and veins. 2. Maltron: bio-electronic impedance analyze 3. Remote monitoring of the high risk patients to become a more intensive follow-up Number of inclusions: 2000 pregnant women from the prenatal consultations of eight different hospitals:

Study of Pregnancy Pathologies Associated With Placental Abnormalities

Pregnancy pathologies can occur from implantation until childbirth. The investigators are interested in the development mechanisms of these pathologies and aim to develop therapies to treat them. The investigators need to collect samples, especially placental samples, following abortions and term and premature deliveries. Abortions will allow investigators to have non-pathological placental material up to 13 weeks. This material will serve as a reference for the understanding of the histological changes that occur in normal placentas collected at term of pregnancy. The latter will, in turn, be compared with the placentas collected during premature deliveries. Also, the abortion product will be cultivated in an environment mimicking the pathology of pre-eclampsia. This study will allow investigators to advance their understanding of the pathophysiological mechanisms of the placenta. The investigators are internationally recognized for their research on these pathologies.