Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis - Clinical Trial for Chronic Histiocytic Intervillositis | NCT05936333

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Primary Purpose

Status

Not yet recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Biological collection

About this trial

This is an interventional basic science trial for Chronic Histiocytic Intervillositis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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)

Sites / Locations

Antoine Béclère Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Patient with chronic histiocytic intervillositis

patients with anti-phospholipid syndromes (APS)

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

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

to measure the correlation between fetus-specific antibody level by Mean Fluorescence Intensity and the severity and/or precocity of obstetrical complications

measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis

measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis

To measure the expression of HLA class I and II molecules by placental villi by ß2-microglobulin and HLA-DR labelling

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

Full Information

NCT ID

NCT05936333

First Posted

June 12, 2023

Last Updated

June 30, 2023

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT05936333

Brief Title

Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis

Acronym

RH-PL

Official Title

Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

July 2023 (Anticipated)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Histiocytic Intervillositis, Intrauterine Growth Retardation, Fetal Death in Utero, Miscarriage

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Patient with chronic histiocytic intervillositis

Arm Type

Experimental

Arm Description

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

Arm Title

patients with anti-phospholipid syndromes (APS)

Arm Type

Active Comparator

Arm Description

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

Arm Title

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

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Procedure

Intervention Name(s)

Biological collection

Intervention Description

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

Primary Outcome Measure Information:

Title

Proportion of patients diagnosed with CHI, defined by the concomitant presence of the 3 criteria required to evoke humoral alloimmune rejection for this pathology

Description

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.

Time Frame

up to 6 months

Secondary Outcome Measure Information:

Title

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

Title

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

Title

measure of semi-quantitative graduation of C4d in placenta compared to percentage of villositis

Time Frame

up to 6 months

Title

measure of semi-quantitative graduation of CD68+ infiltrate in placenta compared to surface and number of involved villositis

Time Frame

up to 6 months

Title

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

Title

Epitope analysis with algorithm developped by laboratoire HLA de St Louis (Pr JL Taupin)

Description

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

Time Frame

up to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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: 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alexandra LETOURNEAU, Doctor

Phone

331 45 37 44 76

Email

letourneau.alexandra@aphp.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Alexandra BENACHI, Professor

Phone

331 45 37 44 76

Email

alexandra.benachi@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexandra LETOURNEAU, Doctor

Organizational Affiliation

APHP, Antoine Béclère Hospital, CLAMART, France

Official's Role

Principal Investigator

Facility Information:

Facility Name

Antoine Béclère Hospital

City

Clamart

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alexandra BENACHI, Professor

12. IPD Sharing Statement

Plan to Share IPD

No

Exploration of Allograft Humoral Rejection in Chronic Histiocytic Intervillositis (RH-PL)

Chronic Histiocytic Intervillositis, Intrauterine Growth Retardation, Fetal Death in Utero

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial