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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04705935
Other study ID # AU011020
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date August 15, 2022
Est. completion date July 2024

Study information

Verified date December 2023
Source University of Aarhus
Contact Emmeli Mikkelsen, MD
Phone +45 29652328
Email emmeli.mikkelsen@clin.au.dk
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Globally, preterm birth (15 mill. per year) is the leading cause of under-5 child mortality (1 mill. per year) and morbidity. Important pathways include preterm labor contractions, Preterm Prelabor Rupture of the Fetal Membranes (PPROM), and iatrogenic delivery. At labor, the fetal amniochorionic membrane undergoes a cellular senescence and shed fetal amniochorionic membrane cells (ACM cells) to the maternal circulation. In collaboration with the private firm ARCEDI Biotech and The University of Texas Medical Branch at Galveston, Aarhus University has identified specific antibodies, which can be used to isolate ACM cells from maternal blood. Thus, the aim of this study is 1) to characterize ACM cells by histological and immunological techniques, and 2) in a cohort assess their performance as biomarkers of amniochorionic membrane dysfunction, including early detection of threatening preterm birth. In perspective, the findings are expected to improve the diagnostics and treatment of preterm birth.


Description:

Aim: The aim of the study is 1) to characterize circulating fetal amniochorionic membrane cells (ACM cells) in pregnant women and 2) to investigate if they can function as biomarkers of amniochorionic membrane dysfunction, including risk of preterm birth. Background: Globally, preterm birth (15 mill. per year) is the leading cause of under-5 child mortality (1 mill. per year) and morbidity. Important pathways include preterm labor contractions (PLC), Preterm Prelabor Rupture of the Fetal Membranes (PPROM), and iatrogenic delivery due to preeclampsia and fetal growth restriction. At labor, the fetal amniochorionic membrane undergoes a cellular senescence and shed fetal amniochorionic membrane cells (ACM cells) to the maternal circulation. Similar features are expected to be seen in cases with PPROM. In collaboration with ARCEDI Biotech Aps and the University of Texas Medical Branch at Galveston, Aarhus University has identified specific fetal membrane cell markers, i.e. specific proteins highly expressed by the ACM cells. Commercially available antibodies specific for these identified proteins can be used to isolate ACM cells from the maternal blood. The preliminary studies indicate that circulating ACM cells are present in the second half of pregnancy but not in the first half of pregnancy. The investigators want to confirm by immunohistochemistry that specific antibodies can identify ACM cells in the fetal membranes, and that they can be a platform for isolating ACM cells from the maternal circulation. Materials and Methods: The investigators will isolate ACM cells from maternal blood by Magnetic Activating Cell Sorting (MACS) using different specific antibodies for ACM cells. The enriched ACM cells will be stained using fluorescent-labeled cytokeratin and vimentin antibodies, and sorted individually by Fluorescence Activated Cell Sorting (FACS). The true identification of the fetal derived ACM cells will be done by Short Tandem Repeat (SRT) analysis. The antibodies that perform best will be selected based on pilot studies on pregnant women at term and in gestation week 12, 20, 28 and 34, as well as at labor and post partum. The protein expression and specificity of each antibody will be confirmed by immunohistochemistry and bright field microscopy on biopsies from the fetal membranes, placental tissue, and the placental bed in the uterus. The established protocol will be used to evaluate the number of ACM cells in the maternal blood in normal and pathological pregnancies on cross sectional cohorts of term pregnant women with and without labor contractions and spontaneous rupture of membranes, women with PLC before 34 weeks gestation, women with PPROM before 34 weeks gestation, and a control group at gestational age 25+0 to 37. Perspectives: In the future, the results are expected to improve the diagnostics and treatment of threatening preterm birth, thus preventing mortality and morbidity in millions of children worldwide.


Recruitment information / eligibility

Status Recruiting
Enrollment 500
Est. completion date July 2024
Est. primary completion date July 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria: - Normal pregnancy at term (> 37 weeks) the day before a planned caesarean section. - Normal pregnancy at term (> 37 weeks) with planned vaginal delivery. - Women with preterm labor contractions < 34 weeks admitted at the hospital. - Women with PPROM < 34 weeks admitted at the hospital. - Normal pregnancy at gestational age 25+0 to 37. - Normal pregnancy at gestational age 12 included at the nuchal translucency scan. - Normal pregnancy at birth. Exclusion Criteria: - Maternal age < 18 - Women who does not understand the oral or written information - Women who does not speak Danish - Women who does not want to participate - Women with complications in pregnancy

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Denmark Aarhus University Hospital Aarhus

Sponsors (5)

Lead Sponsor Collaborator
University of Aarhus Aarhus University Hospital, ARCEDI Biotech, Medical University of Graz, The University of Texas Medical Branch, Galveston

Country where clinical trial is conducted

Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Other Maternal age Years At inclusion
Other Maternal BMI kg/m At inclusion
Primary ACM cells in maternal blood Number At inclusion
Secondary Gestational age at delivery Weeks+days At delivery
Secondary Birth weight of child Kg At delivery
Secondary APGAR score <4, 4-7, or >7 At delivery
Secondary Sex of child M/F At delivery
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