Preterm BirthNCT04705935
Amniochorionic Membrane Cells in the Maternal Blood as a Biomarker for Preterm Birth
An observational study of Preterm Birth and Preterm Premature Rupture of Membrane, run by University of Aarhus at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth, Preterm Premature Rupture of Membrane, Preterm Labor
- How many people
- 83 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Aug 2022to 28 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Pregnant women who complies to the above mentioned inclusion and exclusion criteria.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Keywords
- Amniochorionic Membrane Cells, Fetal Membrane Cells
- Medical subject headings
- Premature Birth, Preterm Premature Rupture of the Membranes, Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Term pregnant women without labor contractions or rupture of membranes | Term pregnant women > 37 weeks gestation with a normal pregnancy. One blood sample before a scheduled caesarean section. | |
| Term pregnant women with labor contractions | Term pregnant women > 37 weeks gestation with a normal pregnancy. One blood sample when labor contractions, but before spontaneous rupture of membranes. | |
| Term pregnant women with spontaneous rupture of membranes | Term pregnant women > 37 weeks gestation with a normal pregnancy. One blood sample after spontaneous rupture of membranes, but without labor contractions. | |
| Preterm labor contractions (PLC) | One blood sample when labor contractions before 34 weeks gestation without rupture of membranes. | |
| Preterm Prelabor Rupture of the Fetal Membranes (PPROM) | One blood sample when rupture of the fetal membranes before 34 weeks gestation without labor contractions. | |
| Control group | Women with normal pregnancies. One blood sample in gestation week 25+0 to 37 matched as controls for PLC and PPROM cases. | |
| Longitudinal cohort during pregnancy | Women with normal pregnancies, where blood samples will be collected at week 12, 20, 28, 34 and 36, as well as at labor. | |
| Longitudinal cohort post partum | Women with normal pregnancies, where blood samples will be collected at labor, as well as 2 days, and 4, 8 and 12 weeks after birth. |
What is being measured
The primary outcome is the main question the study is designed to answer.
ACM cells in maternal blood
Number
Measured: At inclusion
Secondary outcomes (4)
Gestational age at delivery
Weeks+days
Measured: At delivery
Birth weight of child
Kg
Measured: At delivery
APGAR score
<4, 4-7, or >7
Measured: At delivery
Sex of child
M/F
Measured: At delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2021
- Study start15 Aug 2022
- Primary completion28 Jun 2024
- Study completion28 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Arcedi Biotech, Aarhus University Hospital, The University of Texas Medical Branch, Galveston, Medical University of Graz
- Responsible party
- Principal investigator, Niels Uldbjerg, University of Aarhus
- Investigators
- Ramkumar Menon, PhD, Study chair, The University of Texas Medical Branch, GalvestonTorben Steiniche, DMSc, Study chair, Aarhus University HospitalPalle Schelde, MSc, Principal investigator, Arcedi BiotechRipudaman Singh, PhD, Study chair, Arcedi BiotechBerthold Huppertz, PhD, Study chair, Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04705935
- Sponsor's protocol ID
- AU011020
- Status last verified
- Dec 2024
- First submitted
- 1 Dec 2020
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amniochorionic Membrane Cells in the Maternal Blood as a Biomarker for Preterm Birth
- ClinicalTrials.gov ID
- NCT04705935
- Acronym / sponsor ID
- AU011020
- Keywords
- Amniochorionic Membrane Cells, Fetal Membrane Cells
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Arcedi Biotech, Aarhus University Hospital, The University of Texas Medical Branch, Galveston, Medical University of Graz
- Study start
- 15 Aug 2022 (actual)
- Primary completion
- 28 Jun 2024 (actual)
- Study completion
- 28 Jun 2024 (actual)
- First posted
- 12 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Term pregnant women without labor contractions or rupture of membranes | – | –Term pregnant women > 37 weeks gestation with a normal pregnancy. One blood sample before a scheduled caesarean section. |
| Term pregnant women with labor contractions | – | –Term pregnant women > 37 weeks gestation with a normal pregnancy. One blood sample when labor contractions, but before spontaneous rupture of membranes. |
| Term pregnant women with spontaneous rupture of membranes | – | –Term pregnant women > 37 weeks gestation with a normal pregnancy. One blood sample after spontaneous rupture of membranes, but without labor contractions. |
| Preterm labor contractions (PLC) | – | –One blood sample when labor contractions before 34 weeks gestation without rupture of membranes. |
| Preterm Prelabor Rupture of the Fetal Membranes (PPROM) | – | –One blood sample when rupture of the fetal membranes before 34 weeks gestation without labor contractions. |
| Control group | – | –Women with normal pregnancies. One blood sample in gestation week 25+0 to 37 matched as controls for PLC and PPROM cases. |
| Longitudinal cohort during pregnancy | – | –Women with normal pregnancies, where blood samples will be collected at week 12, 20, 28, 34 and 36, as well as at labor. |
| Longitudinal cohort post partum | – | –Women with normal pregnancies, where blood samples will be collected at labor, as well as 2 days, and 4, 8 and 12 weeks after birth. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant women who complies to the above mentioned inclusion and exclusion criteria.
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
ACM cells in maternal blood
Time frame: At inclusion
Number
4 secondary outcomes
Gestational age at delivery
Time frame: At delivery
Birth weight of child
Time frame: At delivery
APGAR score
Time frame: At delivery
Sex of child
Time frame: At delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramkumar Menon, PhD study chair
The University of Texas Medical Branch, Galveston
Torben Steiniche, DMSc study chair
Aarhus University Hospital
Palle Schelde, MSc principal investigator
Arcedi Biotech
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preterm Birth and Preterm Premature Rupture of Membrane, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACM cells in maternal blood (time frame: At inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.