Pre-EclampsiaGrossNETsNCT05470712
Vital Mechanism of NETs Formation vs. Suicidal Mechanism of NETs Formation During Normal Pregnancy and Preeclampsia
An observational study of Pre-Eclampsia, run by Centre Hospitalier Universitaire de Nīmes at 1 site in France.
Trial summary
Formation of neutrophil extracellular traps (NETs) is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pre-Eclampsia
- How many people
- 26 participants
- Where
- 1 siteFrance
- Study dates
- 20 Jul 2022to 31 Dec 2022
- 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
- No healthy volunteers
- Adult, Older adult
Study population: The study is based on frozen plasma samples from pregnant women, taken at the time of them giving birth from among the 85 women who constituted the previous cohort (NCT01736826). Thirteen of these women had had normal pregnancies and thirteen had developed pre-eclampsia. Cases are matched on maternal age, clinical event (delivery) and gestational age will be included from the previous cohort (NCT01736826).
Who may be able to join
- The inclusion criteria for the previous cohort (NCT01736826) were:
- pregnant women followed at Nimes University hospital for normal pregnancy or pregnancy with placental vascular pathology (pre-eclampsia and/or intra-uterine growth retardation).
- The patient must have given her free and informed consent and signed the consent form.
- The patient must be a member or beneficiary of a health insurance plan
- Only women are included
- Patients are at least 18 years old
Who cannot join
- Not applicable as this is a study on samples from a biobank. The non-inclusion criteria of the previous cohort (NCT01736826) were :
- twin pregnancies.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Retrospective Study of Vital Mechanism of NETs Formation vs. Suicidal Mechanism of NETs Formation During Normal Pregnancy and Preeclampsia
Formation of neutrophil extracellular traps (NETs) is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism, dependent on the reactive oxygen species (ROS) pathway. The description of these two mechanisms of formation of NETs is recent and no data exist in the context of pregnancy.
Read the detailed description
This is a descriptive pilot study on a ready-constituted biobank. It is an ancillary study to a previous cohort (RCB number: 2014-A01120-47, NCT01736826).
Pregnancy generates an increased risk of thrombosis, and placenta-mediated diseases constitute a risk factor for cardiovascular pathologies responsible for significant maternal-fetal morbidity and mortality. Understanding and exploring the cellular and molecular mechanisms of dysfunctions of the vascular-placental interface could provide arguments to understand the systemic vascular risk, characterize it and finally detect it on the basis of new markers, thus opening the way for targeted preventive management to reinforce the general principles of precision medicine.
Formation of NETs is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Formation of NETs occurs in pregnancy and is increased in vascular-placental complications. It can be studied by measuring circulating histones, particularly the citrullinated histone H3. Levels of this modified histone H3, as well as those of two other modifications, have recently been shown to increase during pregnancy. These levels have also been shown to be even greater in pregnancy complications.
Furthermore, two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism, dependent on the reactive oxygen species (ROS) pathway. The description of these two mechanisms of formation of NETs is recent and no data exist in the context of pregnancy.
The aim of this study is to describe the part of these two mechanisms in normal and complicated pre-eclampsia pregnancies in order to obtain a better physiopathological knowledge of pre-eclampsia to propose new circulating biomarkers and to develop new therapeutic strategies for placental vascular pathologies.
- Conditions
- Pre-Eclampsia
- Keywords
- Pregnancy, Pre-eclampsia, Neutrophils, Extracellular traps
- Medical subject headings
- Pre-Eclampsia
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 |
|---|---|---|
| Plasma from women with preeclampsia | Plasma collected from women who developed preeclampsia during pregnancy will be analyzed for mechanism of NETs formation. | |
| Plasma from women with normal pregnancies | Plasma collected from women with normal pregnancies will be analyzed for mechanism of NETs formation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia.
Evaluation of vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia.
Measured: 3 months
Secondary outcomes (8)
To compare the proportion of vital mechanism of NETs formation in the presence or absence of a TLR-blocking antibody within each group: normal pregnancy and preeclamptic pregnancy.
Evaluation of the proportion of vital mechanism of NETs formation in the presence or absence of a TLR-blocking antibody within each group: normal pregnancy and preeclamptic pregnancy.
Measured: 3 months
To compare the proportion of vital mechanism of NETs formation in the presence of a TLR-blocking antibody between pregnant women with normal pregnancies and those developing preeclampsia.
Evaluation of the proportion of vital mechanism of NETs formation in the presence of a TLR-blocking antibody between pregnant women with normal pregnancies and those developing preeclampsia.
Measured: 3 months
To compare vital and suicidal mechanisms of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
Evaluation of vital and suicidal mechanisms of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
Measured: 3 months
To compare vital and suicidal mechanisms of NETs formation in the presence or absence of a TLR blocking antibody or ROS inhibitor (DPI) separately within each group: normal pregnancy and preeclamptic pregnancy.
Evaluation of vital and suicidal mechanisms of NETs formation in the presence or absence of a TLR blocking antibody or ROS inhibitor (DPI) separately within each group: normal pregnancy and preeclamptic pregnancy.
Measured: 3 months
To compare vital and suicidal mechanisms of NETs formation in the presence of TLR blocking antibody or ROS inhibitor (DPI) between pregnant women with normal pregnancy and those developing preeclampsia.
Evaluation of vital and suicidal mechanisms of NETs formation in the presence of TLR blocking antibody or ROS inhibitor (DPI) between pregnant women with normal pregnancy and those developing preeclampsia.
Measured: 3 months
To compare the proportion of suicidal mechanism of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
Evaluation of the proportion of suicidal mechanism of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
Measured: 3 months
To compare suicidal mechanism of NETs formation in the presence or absence of ROS inhibitor (PGD) separately within each group: normal pregnancy and preeclamptic pregnancy.
Evaluation of suicidal mechanism of NETs formation in the presence or absence of ROS inhibitor (PGD) separately within each group: normal pregnancy and preeclamptic pregnancy.
Measured: 3 months
To compare the proportion of suicidal mechanism of NETs formation in the presence of an ROS inhibitor (PGD) between pregnant women with a normal pregnancy and those developing preeclampsia.
Evaluation of the proportion of suicidal mechanism of NETs formation in the presence of an ROS inhibitor (PGD) between pregnant women with a normal pregnancy and those developing preeclampsia
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start20 Jul 2022
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NīmesThe 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nīmes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anissa MEGZARI, Study chair, CHU Nimes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05470712
- Sponsor's protocol ID
- NIMAO/2022-1/SB-01
- Acronym
- GrossNETs
- Status last verified
- Feb 2023
- First submitted
- 20 Jul 2022
- Last updated
- 4 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Guillotin F, Fortier M, Portes M, Demattei C, Mousty E, Nouvellon E, Mercier E, Chea M, Letouzey V, Gris JC, Bouvier S. Vital NETosis vs. suicidal NETosis during normal pregnancy and preeclampsia. Front Cell Dev Biol. 2023 Jan 5;10:1099038. doi: 10.3389/fcell.2022.1099038. eCollection 2022.
PubMed 36684420
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Retrospective Study of Vital Mechanism of NETs Formation vs. Suicidal Mechanism of NETs Formation During Normal Pregnancy and Preeclampsia
- ClinicalTrials.gov ID
- NCT05470712
- Acronym / sponsor ID
- GrossNETs / NIMAO/2022-1/SB-01
- Conditions
- Pre-Eclampsia
- Keywords
- Pregnancy, Pre-eclampsia, Neutrophils, Extracellular traps
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NīmesUniversity, hospital or other
- Study start
- 20 Jul 2022 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 22 Jul 2022 (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.
Formation of neutrophil extracellular traps (NETs) is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism, dependent on the reactive oxygen species (ROS) pathway. The description of these two mechanisms of formation of NETs is recent and no data exist in the context of pregnancy.
Detailed description
This is a descriptive pilot study on a ready-constituted biobank. It is an ancillary study to a previous cohort (RCB number: 2014-A01120-47, NCT01736826).
Pregnancy generates an increased risk of thrombosis, and placenta-mediated diseases constitute a risk factor for cardiovascular pathologies responsible for significant maternal-fetal morbidity and mortality. Understanding and exploring the cellular and molecular mechanisms of dysfunctions of the vascular-placental interface could provide arguments to understand the systemic vascular risk, characterize it and finally detect it on the basis of new markers, thus opening the way for targeted preventive management to reinforce the general principles of precision medicine.
Formation of NETs is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Formation of NETs occurs in pregnancy and is increased in vascular-placental complications. It can be studied by measuring circulating histones, particularly the citrullinated histone H3. Levels of this modified histone H3, as well as those of two other modifications, have recently been shown to increase during pregnancy. These levels have also been shown to be even greater in pregnancy complications.
Furthermore, two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism, dependent on the reactive oxygen species (ROS) pathway. The description of these two mechanisms of formation of NETs is recent and no data exist in the context of pregnancy.
The aim of this study is to describe the part of these two mechanisms in normal and complicated pre-eclampsia pregnancies in order to obtain a better physiopathological knowledge of pre-eclampsia to propose new circulating biomarkers and to develop new therapeutic strategies for placental vascular pathologies.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plasma from women with preeclampsia | – | –Plasma collected from women who developed preeclampsia during pregnancy will be analyzed for mechanism of NETs formation. |
| Plasma from women with normal pregnancies | – | –Plasma collected from women with normal pregnancies will be analyzed for mechanism of NETs formation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study is based on frozen plasma samples from pregnant women, taken at the time of them giving birth from among the 85 women who constituted the previous cohort (NCT01736826). Thirteen of these women had had normal pregnancies and thirteen had developed pre-eclampsia. Cases are matched on maternal age, clinical event (delivery) and gestational age will be included from the previous cohort (NCT01736826).
Key inclusion criteria (6 listed)
- pregnant women followed at Nimes University hospital for normal pregnancy or pregnancy with placental vascular pathology (pre-eclampsia and/or intra-uterine growth retardation).
- The patient must have given her free and informed consent and signed the consent form.
- The patient must be a member or beneficiary of a health insurance plan
- Only women are included
- Patients are at least 18 years old
Key exclusion criteria (2 listed)
- Not applicable as this is a study on samples from a biobank. The non-inclusion criteria of the previous cohort (NCT01736826) were :
- twin pregnancies.
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
To evaluate vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia.
Time frame: 3 months
Evaluation of vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia.
8 secondary outcomes
To compare the proportion of vital mechanism of NETs formation in the presence or absence of a TLR-blocking antibody within each group: normal pregnancy and preeclamptic pregnancy.
Time frame: 3 months
To compare the proportion of vital mechanism of NETs formation in the presence of a TLR-blocking antibody between pregnant women with normal pregnancies and those developing preeclampsia.
Time frame: 3 months
To compare vital and suicidal mechanisms of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
Time frame: 3 months
To compare vital and suicidal mechanisms of NETs formation in the presence or absence of a TLR blocking antibody or ROS inhibitor (DPI) separately within each group: normal pregnancy and preeclamptic pregnancy.
Time frame: 3 months
To compare vital and suicidal mechanisms of NETs formation in the presence of TLR blocking antibody or ROS inhibitor (DPI) between pregnant women with normal pregnancy and those developing preeclampsia.
Time frame: 3 months
To compare the proportion of suicidal mechanism of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
Time frame: 3 months
To compare suicidal mechanism of NETs formation in the presence or absence of ROS inhibitor (PGD) separately within each group: normal pregnancy and preeclamptic pregnancy.
Time frame: 3 months
To compare the proportion of suicidal mechanism of NETs formation in the presence of an ROS inhibitor (PGD) between pregnant women with a normal pregnancy and those developing preeclampsia.
Time frame: 3 months
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 4 Dec 2025.
- Results publication: PubMed 36684420Guillotin F, Fortier M, Portes M, Demattei C, Mousty E, Nouvellon E, Mercier E, Chea M, Letouzey V, Gris JC, Bouvier S. Vital NETosis vs. suicidal NETosis during normal pregnancy and preeclampsia. Front Cell Dev Biol. 2023 Jan 5;10:1099038. doi: 10.3389/fcell.2022.1099038. eCollection 2022.
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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.
Anissa MEGZARI study chair
CHU Nimes
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 Pre-Eclampsia, run by Centre Hospitalier Universitaire de Nīmes at 1 site in France.
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 6 inclusion and 2 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 4 Dec 2025. 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 France. 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?
To evaluate vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05470712, which also lists 1 linked publication.
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 4 Dec 2025.