Search Tolerance Signature in Vascularised Composite Allograft (BIOCTA)

Composite tissue allotransplants (CTA) involve transplantation of various tissues including vessels, nerves, skin, bones, and immune cells and entail a significant antigenic load. The large majority of recipients have been maintained on immunosuppression therapy similar to that used in solid organ transplantation that is associated with the complications usually reported in solid organ transplantation. The question whether risks associated with indefinite immunosuppressive are justified for a non-lifesaving procedure still remains unanswered. At present no CTA recipient proved to be spontaneously tolerant with any immunosuppressive protocol; indeed, until now all recipients who discontinued the immunosuppressive therapy rejected their graft. On the other hand CTA recipients showed a low incidence of chronic rejection despite the high incidence of acute rejection episodes.

For all these reasons it should be of great interest to minimize the immunosuppression in CTA patients knowing their immunologic "risk". The main outcome of this study is to search for the signature of tolerance in recipients of hand or face allotransplantation testing biomarkers previously identified in operational tolerant kidney transplant recipients.

These markers have been developed studying tolerant kidney recipients and they were already tested in five bilateral hand transplantations and one face transplantation.

The present study will include hand and face allograft recipients transplanted at least one year in several European institutions (Innsbruck, Lyon, Monza, Valencia): 11 bilateral hand transplantations, 4 single hand transplantations and 3 face transplantations. All the patients will undergo B cell phenotyping, TCR repertoire, molecular signature from operational tolerance and a skin biopsy with immunohistochemical staining of the specimens in order to show signs of acute or chronic rejection.

The results could provide a valid tool to detect operationally tolerant recipients as well as recipients prone to develop chronic rejection.

Study Overview

• Status: Completed
• Conditions: Hand and Face Allotransplantation
• Intervention / Treatment: Procedure: Blood sample, biopsy

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69003
    • Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient with Hand (unilateral/bilateral) or face allotransplantation for at least one year
• Patient without clinical sign of acute rejection at inclusion
• Patient who signed the informed protocol consent
• Patient older than 18 years old
• Patient covered by an health insurance
• Patient without legal protection

Exclusion Criteria:

• Patient with Hand or face allotransplantation for less than one year
• Patient with clinical sign of acute rejection at inclusion
• Unsigned protocol consent
• Patient under the age of 18 years old

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of molecular signature from operational tolerance and/or chronic rejection research	B cell phenotyping, TCR repertoire, molecular signature from operational tolerance	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological characteristics of skin acute/chronic rejection on skin biopsy	skin biopsy with immunohistochemical staining of the specimens in order to show signs of acute or chronic rejection. We will try to correlate the signature of tolerance with the absence of chronic rejection symptoms, both clinically and in skin protocol biopsies.	1 day
Phenotype of skin T lymphocyte in cutaneous biopsies		1 day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Collaborators: Hospital Clínico Universitario de Valencia; ISTITUTO ITALIANO CHIRURGIA DELLA MANO, Italy; medizinische universität innsbruck, Austria

Publications and helpful links

General Publications

• Emmanuel Morelon, Sophie BROUARD, Stephan Schneeberger, Anne-Marie Weissenbache. Abstract accepted for presentation at the IHCTAs Congress (Philadelphia, April 2015) and at the ESOT Congress (Brussels, September 2015)."

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 17, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimated): February 5, 2014

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: operational tolerance; Composite tissue allograft; skin rejection; Hand and Face allotransplantation
• Additional Relevant MeSH Terms: Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Blood Specimen Collection; Biopsy; Phlebotomy
• Other Study ID Numbers: 2013.815