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.
