Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis

NCT ID: NCT05936333

Last Updated: 2024-11-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-11
• Study Completion Date: 2025-10-11

Brief 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. 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Patient with chronic histiocytic intervillositis

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

Group Type: EXPERIMENTAL

Biological collection

Intervention Type: PROCEDURE

up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth

patients with anti-phospholipid syndromes (APS)

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

Group Type: ACTIVE_COMPARATOR

Biological collection

Intervention Type: PROCEDURE

up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth

women with a third full-term pregnancy without growth retardation.

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

Group Type: PLACEBO_COMPARATOR

Biological collection

Intervention Type: PROCEDURE

up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth

Interventions

Biological collection

up to 25 mL of blood collection for the adults and saliva collection for the minor at inclusion, and placenta collection at childbirth

Intervention Type: PROCEDURE

Eligibility Criteria

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:

o 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:

o Father of the last pregnancy and of the child(ren) participating in the study

Exlusion criteria :

• For mothers in the normal pregnancy group:

o 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandra LETOURNEAU, Doctor

Role: PRINCIPAL_INVESTIGATOR

APHP, Antoine Béclère Hospital, CLAMART, France

Locations

Antoine Béclère Hospital

Clamart, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Alexandra LETOURNEAU, Doctor

Role: CONTACT

letourneau.alexandra@aphp.fr

331 45 37 44 76

Alexandra BENACHI, Professor

Role: CONTACT

alexandra.benachi@aphp.fr

331 45 37 44 76

Facility Contacts

Alexandra LETOURNEAU, Doctor

Role: primary

Alexandra BENACHI, Professor

Role: backup

Other Identifiers

APHP221169

Identifier Type: -

Identifier Source: org_study_id