Molekulare Untersuchung der Schnittstelle zwischen Mutter und Fötus bei Präeklampsie. (PREMAFE)
Molekulare Untersuchung der Schnittstelle zwischen Mutter und Fötus prospektiv bis zum Auftreten einer Präeklampsie mithilfe der Einzelzelltechnologie.
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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
- Verfahren: Maternal-fetal interface biopsy and peripheral blood collection in cases group
- Verfahren: Maternal-fetal interface biopsy and peripheral blood collection in control group
- Verfahren: Maternal-fetal interface biopsy and peripheral blood collection in cases group
- Verfahren: Maternal-fetal interface biopsy and peripheral blood collection in control group
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Geschätzt)
Kontakte und Standorte
Studienkontakt
- Name: Carlos Simón, MD, PhD
Studieren Sie die Kontaktsicherung
- Name: Érika Ortiz, BSc, MSc
- Telefonnummer: +34962938210
- E-Mail: clinicalstudies@fundacioncarlossimon.com
Studienorte
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Alicante
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Alicante, Alicante, Spanien
- Rekrutierung
- 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
- Rekrutierung
- 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
- Rekrutierung
- 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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Unterermittler:
- Walter Plasencia Acevedo
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Valencia
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Valencia, Valencia, Spanien
- Rekrutierung
- 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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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
The study population will consist of women aged 18 years or older with singleton pregnancies who, depending on their stage of pregnancy and willingness to participate, may be enrolled in one or both phases of the study:
- Phase 1 (first trimester): Women attending the participating referral centers between 9 and 15 weeks of gestation to undergo chorionic villus sampling (CVS), either due to an increased risk of fetal chromosomal abnormalities identified through non-invasive prenatal screening or for any other medical indication. In these cases, participants will be asked to donate surplus chorionic villus tissue obtained during the diagnostic procedure, as well as a peripheral blood sample.
- Phase 2 (delivery): Women who, regardless of whether they participated in the initial phase of the study, agree to donate placental tissue and maternal blood samples at the time of delivery. Participation in this phase may be offered at later stages of pregnancy.
Beschreibung
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.
- Women who meet at least one of the following criteria at the time of inclusion:
Phase 1 (first trimester): Pregnant women between 9 and 15 weeks of gestation who are scheduled to undergo chorionic villus sampling (CVS) as part of the center's routine clinical practice.
Phase 2 (delivery): Women with an ongoing pregnancy, regardless of gestational age and without the requirement of having participated in Phase 1, who are willing to donate placental and maternal blood samples following delivery.
Exclusion Criteria:
- Women with multiple pregnancy.
- Non-evolving pregnancies (including delayed abortion/foetal orbit).
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Beobachtungsmodelle: CASE_CONTROL
- Zeitperspektiven: PROSPECTIVE
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
|
Cases group (phase 1)
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. Maternal-fetal interface tissue (placenta) and peripheral blood will be collected from women who develop preeclampsia or other obstetric complication at the end of their pregnancy. Clinical data will be compiled. |
|
Control group (phase 1)
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. Maternal-fetal interface tissue (placenta) and peripheral blood will be collected from women who do not experience any complications or who do not experience the specific obstetric complication defined in the case group to which they are compared. |
|
Cases group (phase 2)
Women recruited at delivery with preeclampsia or other complication. |
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. Maternal-fetal interface tissue (placenta) and peripheral blood will be collected from women who develop preeclampsia or other obstetric complication at the end of their pregnancy. Clinical data will be compiled. |
|
Control group (phase 2)
Women recruited at delivery with no obstetric complication or who do not experience the specific obstetric complication defined in the case group to which they are compared. |
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. Maternal-fetal interface tissue (placenta) and peripheral blood will be collected from women who do not experience any complications or who do not experience the specific obstetric complication defined in the case group to which they are compared. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
To charactize the molecular profile of the maternal-fetal interface (chorionic billi and decidua) between 9 and 15 weeks of gestation in healthy and preeclamptic pregnancies
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
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
Zeitfenster: 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 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
Zeitfenster: 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
Zeitfenster: 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
|
|
To characterize the molecular profile of the maternal-fetal interface (placenta) at the end of pregnancy in healthy and preeclamptic pregnancies
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Tamara Garrido, PhD, Fundación Carlos Simon para la investigación en salud de la mujer
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Schwangerschaftskomplikationen
- Bluthochdruck, schwangerschaftsbedingt
- Präeklampsie
- Untersuchungstechniken
- Epidemiologisches Forschungsdesign
- Epidemiologische Methoden
- Forschungsdesign
- Methoden
- Kontrollgruppen
Andere Studien-ID-Nummern
- FCS-IMF-TG-23-03
Plan für individuelle Teilnehmerdaten (IPD)
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