Clinical trial NCT06232668: Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Official title: Molecular Study of the Maternal-fetal Interface Prospectively to the Onset of Preeclampsia Using Single Cell Technology.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Preeclampsia
Keywords: Preeclampsia
Early onset Preeclampsia (EOPE)
First trimester
Chorionic villi
Pregnancy
Molecular study
Decidua
Maternal-fetal interface
Other pregnancy complications
Omic techniques
Lead sponsor: Carlos Simon Foundation
Sponsor class: OTHER
First posted: 2024-01-31
Enrollment: 2084
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women over the age of 18 recruited between 9 and 14 gestational weeks who attend the participating referral centers for a chorionic villus biopsy due to the detection of a foetal chromosomal abnormality risk.

Brief summary: Preeclampsia (PE) is a major obstetric complication with short- and long-term consequences for the mother and the fetus. Early screening tools to reduce its mortality and morbidity, as well as to prevent the life-threatening consequences are needed. Thus, the detection of women at risk of suffering PE is key to apply preventive and treatment strategies. Recently, the maternal contribution to PE based on defective decidualization that prevents the establishment of a functional maternal-fetal interface has been evidenced. The main objective of this study is to identify molecular markers or aberrant maternal-fetal cell types that can be detected early in the development of the disease in chorionic villi collected during gestational weeks 9 to 14. Chorionic villi will be collected from women who have a recommendation for aneuploidy testing. The remaining fragment will be used for this study.

Detailed description: The hypothesis is that those women who develop PE have impaired decidualization associated with shallow cytotrophoblast invasion during the development of the maternal-fetal interface whose molecular profile analysis at the single cell level will allow characterization of PE development prior to the onset of symptoms.

The purposed study is a biomedical, prospective, multicentre, case-control aimed to characterize the molecular profile of the maternal-foetal interface in the first trimester of pregnancy early in the development of preeclampsia using single-cell sequencing technology. Distinguishing the maternal and fetal origin of the chorionic biopsy cells , describing the maternal-foetal interface and deciphering the intercellular communications and altered pathways in PE and other obstetric complications could be suggested as a secondary outcome, as well as the characterization of the blood sample, the epigenome and metabolome of single cells or the validation of markers of the different cell types.

Subjects will be 2084 pregnant women over the age of 18 recruited between 9 and 14 gestational weeks. Patients attending the participating referral centers for a chorionic villus biopsy due to the detection of a foetal chromosomal abnormality risk will provide the leftover chorionic biopsy sample after determination of the risk of trisomies and a peripheral blood sample for genotyping of maternal lymphocytes and circulating cRNA.

Data will be registered in an electronic Case Report Form (eCRF) specifically designed for this study. Monitoring activities and data verification will be performed during the whole study to ensure data quality, integrity and transparency.

The total estimated duration of the study is 36 months, of which the first 24 months will correspond to the recruitment period of the participants.

Eligibility criteria: Inclusion Criteria:

* Patients whose written informed consent approved by the Ethics Committee (EC) has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
* Women over the age of 18 at the time of signing the informed consent form.
* Pregnant women with a single gestation between weeks 9 and 14 of gestation who will undergo a chorionic villus biopsy according to the centre's usual clinical practice.

Exclusion Criteria:

* Women with multiple pregnancy.
* Non-evolving pregnancies (including delayed abortion/foetal orbit).

Primary outcomes:
measure: To charactise the molecular profile of the maternal-fetal interface between 9 and 14 weeks of gestation in healthy and preeclamptic pregnancies
timeFrame: 18 months
Secondary outcomes:
measure: To characterise the molecular profile of the maternal-fetal interface between 9 and 14 weeks of gestation in pregnancies diagnosed with pregnancy complication other than preeclampsia
timeFrame: 18 months
measure: To characterise the epigenome and metabolome of individual cells from the maternal-fetal interface in healthy pregnancies and those diagnosed with preeclampsia or other pregnancy complication
timeFrame: 24 months
measure: The discovery and validation of molecular markers as candidates for early diagnosis and/or therapy
timeFrame: 30 months
Other outcomes:
Locations:
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
affiliation: Fundación Carlos Simon para la investigación en salud de la mujer
name: Tamara Garrido, PhD
role: PRINCIPAL_INVESTIGATOR
References: