DSA Intragraft in Lung Transplantation: Diagnostic and Prognostic Value in Antibody Mediated Rejection

Intérêt Diagnostique et Pronostique de la présence d'Anticorps spécifiques du Donneur Intra-greffon Dans le Rejet Humoral en Transplantation Pulmonaire

The diagnosis of AMR in lung transplant recipients is difficult and often comes too late, because of lack of standardized definition. The diagnosis is nowadays based on an expert multidisciplinary approach involving clinical, histopathological and immunological criteria.

Hypothesis: the presence of intragraft donor specific antibodies (gDSAs) could be used as a new diagnostic tool for AMR in lung transplant recipients Study Objectives: to evaluate, in lung transplant patients with circulating DSAs, the diagnostic value of gDSAs in AMR and to analyze its prognostic value on graft outcome.

Study Overview

• Status: Recruiting
• Conditions: Lung Transplant Recipient; Antibody Mediated Rejection; Donor Specific Antibodies
• Intervention / Treatment: Procedure: bronchoscopy.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandrine HIRSCHI; Phone Number: +33 3 69 55 11 78; Email: sandrine.hirschi@chru-strasbourg.fr

Study Locations

• France
  • Le Plessis Robinson, France, 92350
    • Not yet recruiting
    • Hopital Marie Lannelongue
    • Contact: Jérôme LE PAVEC; Phone Number: +33 1 40 94 24 30; Email: lepavec@gmail.com
  • Marseille, France, 13915
    • Recruiting
    • CHU Nord
    • Contact: Martine REYNAUD GAUBERT; Phone Number: +33 1 40 25 82 37; Email: martine.reynaud@ap-hm.fr
  • Paris, France, 75018
    • Not yet recruiting
    • Hôpital Bichat
    • Contact: Olivier BRUGIERE; Phone Number: +33 1 40 25 82 37; Email: olivier.brugiere@aphp.fr
  • Strasbourg, France, 67091
    • Recruiting
    • Les Hôpitaux Universitaires de Strasbourg
    • Contact: Sandrine HIRSCHI; Phone Number: +33 3 69 55 11 78; Email: sandrine.hirschi@chru-strasbourg.fr
    • Principal Investigator: Sandrine HIRSCHI
  • Suresnes, France, 92151
    • Not yet recruiting
    • Hopital Foch
    • Contact: Antoine ROUX; Phone Number: +33 1 46 25 37 31; Email: a.roux@hopital-foch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patient older than 18 years
• Transplanted pulmonary or cardiopulmonary patient
• And developing circulating anti-HLA antibodies directed against the graft or "DSA" at a threshold > 1000 of MFI in the 30 days preceding the inclusion visit
• Affiliation to the French social security
• Patient able to understand the objectives and risks related to research and to give informed, dated and signed consent

Exclusion criteria:

• Patient whose anti-HLA antibodies are not directed against the graft (no DSA)
• Contraindication to performing a bronchial fibroscopy with transbronchial biopsies
• Treatment with intravenous immunoglobulin (less than 1 month before inclusion) or Rituximab (less than 6 months before inclusion)
• Plasma exchanges (less than 3 months before inclusion)
• Risk of bleeding predictable (crushing disorder, impossibility of stopping the offending treatments)
• Impossibility of giving the subject informed information
• Subject under the protection of justice Subject under guardianship or curatorship
• Pregnancy
• Breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Bronchial fibroscopy; Bronchial fibroscopy with trans-bronchial biopsies	Procedure: bronchoscopy.; gDSAs are studied on cryopreserved biopsies obtained during bronchoscopy. The technique is the one described by Visentin J.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of AMR	Sensitivity and specificity of the presence of gDSA for the diagnosis of AMR in lung transplant recipients with circulating DSA, as established by an expert pathologist panel and in accordance with recent international recommendations	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparaison in gDSA+ vs gDSAs- patients	Incidence of graft loss	2 years

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Anticipated): February 22, 2026
• Study Completion (Anticipated): February 22, 2026

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: February 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 7039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No