Molekylær undersøgelse af den moder-føtale grænseflade i præeklampsi. (PREMAFE)
Molekylær undersøgelse af den moder-føtale grænseflade fremadrettet til begyndelsen af præeklampsi ved hjælp af enkeltcelleteknologi.
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 maternal-fetal interface tissue (chorionic villi + decidua) collected during gestational weeks 9 to 15. Maternal-fetal interface biopsy will be collected from women who have a recommendation for aneuploidy testing. The remaining fragment will be used for this study.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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-fetal 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-fetal 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. Another objective will be to perform a molecular characterization of maternal-fetal blood and tissue samples collected at the time of delivery, with the aim of correlating the alterations detected in the first trimester with the molecular profiles at the end of pregnancy in both PE patients and controls.
Subjects will be 2084 pregnant women over the age of 18 recruited between 9 and 15 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 52 months, of which the first 48 months will correspond to the recruitment period of the participants.
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiekontakt
- Navn: Carlos Simón, MD, PhD
Undersøgelse Kontakt Backup
- Navn: Carla Gómez, BSc, MSc
- Telefonnummer: +34962938210
- E-mail: cgomez@fundacioncarlossimon.com
Studiesteder
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Alicante
-
Alicante, Alicante, Spanien
- Rekruttering
- Hospital General Universitario Dr. Balmis
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Kontakt:
- Ana María Palacios Marqués
- Telefonnummer: 965 93 30 00
- E-mail: ana.palacios.marques@gmail.com
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Murcia
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Murcia, Murcia, Spanien
- Rekruttering
- Hospital Clinico Universitario Virgen de la Arrixaca
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Kontakt:
- Juan Luis Delgado
- Telefonnummer: +34 968 36 96 74
- E-mail: juanluisdelgado@tokos.org
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Santa Cruz de Tenerife
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Santa Cruz de Tenerife, Santa Cruz de Tenerife, Spanien
- Rekruttering
- Hospital Universitario de Canarias
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Kontakt:
- Mercedes Hernández Suárez
- Telefonnummer: 922 67 80 00
- E-mail: mercedes021281@hotmail.com
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Underforsker:
- Walter Plasencia Acevedo
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Valencia
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Valencia, Valencia, Spanien
- Rekruttering
- Hospital Universitario y Politécnico La Fe
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Kontakt:
- Rogelio Monfort Ortiz
- Telefonnummer: +34 961 24 40 00
- E-mail: monfort_isaort@gva.es
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Kontakt:
- Beatriz Marcos Puig
- Telefonnummer: +34 961 24 40 00
- E-mail: marcos_bea@gva.es
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Pregnant women over the age of 18 recruited between 9 and 15 gestational weeks who attend the participating referral centers for a chorionic villus biopsy due to the detection of a foetal chromosomal abnormality risk.
Beskrivelse
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 15 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).
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: CASE_CONTROL
- Tidsperspektiver: PROSPECTIVE
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
|
Cases group
Women recruited between 9 and 15 gestational weeks diagnosed with preeclampsia or other complication at the end of pregnancy. |
Maternal-fetal interface tissue (chorionic villi and decidua) will be collected from women who have a recommendation for aneuploidy testing, and the remaining fragment will be used for this study and peripheral blood collection in cases group. Clinical data will be compiled. |
|
Control group
Women recruited between 9 and 15 gestational weeks without diagnosis of preeclampsia or other complication at the end of the pregnancy |
Maternal-fetal interface tissue (chorionic villi and decidua) will be collected from women who have a recommendation for aneuploidy testing, and the remaining fragment will be used for this study and peripheral blood collection in control group. Clinical data will be compiled. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
To charactize the molecular profile of the maternal-fetal interface between 9 and 15 weeks of gestation in healthy and preeclamptic pregnancies
Tidsramme: From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Differentially expressed genes between control vs preeclampsia group at the level of cell types/subtypes |
From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
To characterise the molecular profile of the maternal-fetal interface between 9 and 15 weeks of gestation in pregnancies diagnosed with pregnancy complication other than preeclampsia
Tidsramme: From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Differentially expressed genes between control vs cases group at the level of cell types/subtypes. |
From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
|
To characterize the molecular profile of the maternal-fetal interface at the end of pregnancy in healthy and preeclamptic pregnancies
Tidsramme: From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Differentially expressed genes between control vs preeclampsia group at the level of cell types/subtypes |
From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
|
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
Tidsramme: From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Differentially methylation profiles and differentially metabolites between control vs cases group at the level of cell types/subtypes. |
From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
|
The discovery and validation of molecular markers as candidates for early diagnosis and/or therapy
Tidsramme: From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Area Under the ROC Curve and/or cell type phenotyping in in vitro cultures after disrupting the candidate |
From the date of enrollment (minimum 9 weeks) until the end of pregnancy (maximum 43 weeks), assessed up to 34 weeks
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Tamara Garrido, PhD, Fundación Carlos Simon para la investigación en salud de la mujer
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- FCS-IMF-TG-23-03
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