Chronic Histiocytic IntervillositisRH-PLNCT05936333
Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis
A study testing Biological collection in people with Chronic Histiocytic Intervillositis and Intrauterine Growth Retardation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Chronic histiocytic intervillositis (CHI) is a rare condition with an incidence of 5 in 10,000 pregnancies. This rare condition is associated with placental inflammatory lesions leading to severe and recurrent obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and miscarriage. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Histiocytic Intervillositis, Intrauterine Growth Retardation, Fetal Death in Utero
- What is being tested?
- Biological collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteFrance
- Study dates
- 11 Oct 2023to 11 Oct 2025
- Phase
- Interventional
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Family Inclusion Criteria:
- Mother and father ≥ 18 years old
- For mothers in the CHI group :
- History of a normal pregnancy (full term, alive child) or IUGR/MFIU or miscarriage(s) or abortion followed by at least 1 obstetrical complication such as IUGR, MFIU, miscarriage
- Diagnosis of chronic histiocytic intervillitis made by placental anatomopathological examination with CD68+ marking
- For the mothers of the antiphospholipid syndrom group
- History of miscarriage(s)
- Having an anti-phospholipid syndrome
- For mothers in the normal pregnancy group:
- Third consecutive pregnancy of normal course, at term (≥ 36 weeks of amenorrhea) with eutrophic child
For the mother and father:
- Consent to participate in the study and for the participation in the study of at least one child and/or the use of existing samples (placenta / fetal DNA) from at least one previous pregnancy with CHI for the CHI group or at least one previous miscarriage for the APS group
For the father:
- Father of the last pregnancy and of the child(ren) participating in the study
Exlusion criteria :
- For mothers in the normal pregnancy group:
- Suspected or confirmed intra-amniotic infection
- For all the mothers:
- History of blood transfusion
- History of allogeneic organ transplantation
- For the mother and the father:
- Person under legal protection (guardianship, curatorship)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Antoine Béclère Hospital
Clamart
Alexandra LETOURNEAU, Doctor
Alexandra BENACHI, Professor
About this study
Chronic histiocytic intervillositis (CHI) is a rare condition with an incidence of 5 in 10,000 pregnancies. This rare condition is associated with placental inflammatory lesions leading to severe and recurrent obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and miscarriage. The pathophysiological mechanisms of CHI are poorly understood, while the empirical treatments prescribed to prevent recurrence are cumbersome and of poor efficacy.
Recent findings suggest that an alloimmune response may play a role. In a recent work, the investigators have demonstrated the role of maternal alloantibodies directed against fetal HLA antigens in two patients followed for recurrent IUGR associated with CHI. Their work suggests that a humoral alloimmune response directed against fetal HLA antigens mimics an allograft rejection process.
The investigators propose to extend the preliminary results obtained in these patients to provide new insights into the pathophysiological mechanisms of CHI, and eventually to predict the risks of fetal loss.
- Conditions
- Chronic Histiocytic Intervillositis, Intrauterine Growth Retardation, Fetal Death in Utero, Miscarriage
- Being tested
- Biological collection
- Medical subject headings
- Fetal Growth Retardation, Stillbirth, Abortion, Spontaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological collectionProcedure or surgery
up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth
| Study group | Role | What they receive |
|---|---|---|
| Patient with chronic histiocytic intervillositis | Experimental | Patient with CHI, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection Receives: Procedure: Biological collection |
| patients with anti-phospholipid syndromes (APS) | Active comparator | Patient with antiphospholipid syndrome, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection Receives: Procedure: Biological collection |
| women with a third full-term pregnancy without growth retardation. | Placebo comparator | Patient with normal pregnancies, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection Receives: Procedure: Biological collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology
Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology, namely CD68+ infiltrate, AND C4d deposits on the trophoblastic villi AND the presence of at least one FSA (fetus-specific antibody, directed against fetal HLA antigens in the maternal blood) with an elevated level, defined by a Mean Fluorescence Intensity (MFI) > 10,000).
This proportion of patients observed in CHI carriers will be compared to the proportion of patients with the concomitant presence of the same 3 criteria observed in the other two control groups.
Measured: up to 6 months
Secondary outcomes (6)
To measure the FSA levels by Mean Fluorescence Intensity for the different obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and abortion for IUGR.
Measured: up to 6 months
to measure the correlation between fetus-specific antibody level by Mean Fluorescence Intensity and the severity and/or precocity of obstetrical complications
Measured: up to 6 months
measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis
Measured: up to 6 months
measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis
Measured: up to 6 months
To measure the expression of HLA class I and II molecules by placental villi by ß2-microglobulin and HLA-DR labelling
Measured: up to 6 months
Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin)
Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin) to determine whether an antibody response against a limited number of epitopes present during a first pregnancy that resulted in a healthy child can explain immunization against both paternal alleles
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2023
- Study start11 Oct 2023
- Primary completion11 Oct 2025 (estimated)
- Study completion11 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Histiocytic IntervillositisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandra LETOURNEAU, Doctor, Principal investigator, APHP, Antoine Béclère Hospital, CLAMART, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05936333
- Sponsor's protocol ID
- APHP221169
- Acronym
- RH-PL
- Status last verified
- Oct 2024
- First submitted
- 12 Jun 2023
- Last updated
- 6 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis
- ClinicalTrials.gov ID
- NCT05936333
- Acronym / sponsor ID
- RH-PL / APHP221169
- Conditions
- Chronic Histiocytic Intervillositis, Intrauterine Growth Retardation, Fetal Death in Utero, Miscarriage
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- 11 Oct 2025 (estimated)
- Study completion
- 11 Oct 2025 (estimated)
- First posted
- 7 Jul 2023 (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.
Chronic histiocytic intervillositis (CHI) is a rare condition with an incidence of 5 in 10,000 pregnancies. This rare condition is associated with placental inflammatory lesions leading to severe and recurrent obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and miscarriage. The pathophysiological mechanisms of CHI are poorly understood, while the empirical treatments prescribed to prevent recurrence are cumbersome and of poor efficacy.
Recent findings suggest that an alloimmune response may play a role. In a recent work, the investigators have demonstrated the role of maternal alloantibodies directed against fetal HLA antigens in two patients followed for recurrent IUGR associated with CHI. Their work suggests that a humoral alloimmune response directed against fetal HLA antigens mimics an allograft rejection process.
The investigators propose to extend the preliminary results obtained in these patients to provide new insights into the pathophysiological mechanisms of CHI, and eventually to predict the risks of fetal loss.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patient with chronic histiocytic intervillositis | Experimental | Procedure: Biological collectionPatient with CHI, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection |
| patients with anti-phospholipid syndromes (APS) | Active comparator | Procedure: Biological collectionPatient with antiphospholipid syndrome, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection |
| women with a third full-term pregnancy without growth retardation. | Placebo comparator | Procedure: Biological collectionPatient with normal pregnancies, as well as her children and their father. Blood collection from the parents, saliva collection (or blood collection) from the children, placenta collection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biological collectionup to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth | Procedure or surgery | Patient with chronic histiocytic intervillositis, patients with anti-phospholipid syndromes (APS), women with a third full-term pregnancy without growth retardation. |
Primary outcome
Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology
Time frame: up to 6 months
Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology, namely CD68+ infiltrate, AND C4d deposits on the trophoblastic villi AND the presence of at least one FSA (fetus-specific antibody, directed against fetal HLA antigens in the maternal blood) with an elevated level, defined by a Mean Fluorescence Intensity (MFI) > 10,000). This proportion of patients observed in CHI carriers will be compared to the proportion of patients with the concomitant presence of the same 3 criteria observed in the other two control groups.
6 secondary outcomes
To measure the FSA levels by Mean Fluorescence Intensity for the different obstetrical complications: intrauterine growth retardation (IUGR), fetal death in utero and abortion for IUGR.
Time frame: up to 6 months
to measure the correlation between fetus-specific antibody level by Mean Fluorescence Intensity and the severity and/or precocity of obstetrical complications
Time frame: up to 6 months
measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis
Time frame: up to 6 months
measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis
Time frame: up to 6 months
To measure the expression of HLA class I and II molecules by placental villi by ß2-microglobulin and HLA-DR labelling
Time frame: up to 6 months
Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin)
Time frame: up to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2024.
- Individual participant dataSharing planned: No
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.
Alexandra LETOURNEAU, Doctor principal investigator
APHP, Antoine Béclère Hospital, CLAMART, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biological collection in people with Chronic Histiocytic Intervillositis and Intrauterine Growth Retardation, run by Assistance Publique - Hôpitaux de Paris 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?
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: status not confirmed, as of the sponsor's last update on 6 Nov 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 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alexandra LETOURNEAU, Doctor (331 45 37 44 76, letourneau.alexandra@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology (time frame: up to 6 months). 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 6 Nov 2024.