Human Craniomaxillofacial Allotransplantation
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|ClinicalTrials.gov Identifier: NCT01889381|
Recruitment Status : Recruiting
First Posted : June 28, 2013
Last Update Posted : October 6, 2017
Background: The human face is critically important for breathing, eating, seeing, and speaking/ communicating, but its most important job may be to look like a human face. Devastating facial deformities often cause affected individuals to avoid human contact and disappear from society. Although current surgical advancements can somewhat restore facial defects, this process often requires many operations and the resulting face only resembles the human face. To date, over 20 face transplants have been performed with highly encouraging functional and aesthetic results, but widespread clinical use has been limited due to the adverse effects of life-long and high-dose immunosuppression needed to prevent graft rejection. Risks include infection, cancer, and metabolic problems, all of which can greatly affect recipients' quality of life, make the procedure riskier, and jeopardize the potential benefits of face transplantation.
Study Design: This non-randomized, Phase II clinical trial will document the use of a new immunomodulatory protocol (aka - Pittsburgh Protocol, Starzl Protocol) for establishing face transplantation as a safe and effective reconstructive treatment for devastating injuries/ defects by minimizing maintenance immunosuppression therapy in face transplant patients. This protocol combines lymphocyte depletion with donor bone marrow cell infusion and has enabled graft survival using low doses of a single immunosuppressive drug followed by weaning of treatment. Initially designed for living-related solid organ donation, this regimen has been adapted for use with grafts donated by deceased donors. The investigators propose to perform 15 full or partial human face transplants employing this novel protocol.
Specific Aims: 1) To establish face transplantation as a safe and effective reconstructive strategy for the treatment of devastating facial injuries/defects; 2) To reduce the risk of rejection and enable allograft survival while minimizing the requirement for long-term, high-dose, multi-drug immunosuppression.
Significance of Research: Face transplantation could help injured individuals recover functionality, self-esteem, and the ability to reintegrate into family and social life as "whole" individuals. This protocol offers the potential for minimizing the morbidity of maintenance immunosuppression, thereby beneficially shifting the risk/benefit ratio of this life-enhancing procedure and enabling a wider clinical application of face transplantation.
|Condition or disease||Intervention/treatment||Phase|
|Facial Injuries Traumatic Wounds and Injuries Craniofacial Injuries Craniofacial Defects||Drug: Bone marrow cell-based therapy & 1-drug immunosuppression.||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Human Craniomaxillofacial Allotransplantation|
|Actual Study Start Date :||August 2012|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||August 2026|
Experimental: Treatment (Transplantation)
Face transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning.
Drug: Bone marrow cell-based therapy & 1-drug immunosuppression.
This protocol uses a novel bone marrow cell-based therapy for composite tissue allotransplantation (CTA) rather than conventional triple-drug immunosuppression to facilitate long-term graft survival of deceased donor human faces under low-dose maintenance immunosuppression. Initial T-cell depletion with alemtuzumab is followed by upper extremity transplantation and tacrolimus maintenance therapy. Donor bone marrow cells are infused on Day 10 (±4 days) post-transplantation to elicit a host alloimmune response triggering exhaustion and deletion of the respective host (anti-donor) lymphocyte clones. Subsequently, tacrolimus therapy is given for at least 6 months before spaced weaning is considered in stable recipients.
Other Name: Deceased donor face transplantation
- Graft Survival [ Time Frame: Transplantation through end of study period (up to 5 years) ]Post-operative graft survival will be documented monthly Months 1-12 and quarterly (every 3 months) Years 2-5.
- Documentation of immunosuppression required by transplanted participants to maintain graft. [ Time Frame: Transplantation to end of study period (up to 5 years) ]Post-operative serum trough levels will be documented daily Days 1-28, semiweekly Weeks 5-12, weekly Weeks 13-25, biweekly Weeks 26-38, monthly Months 10-12, and quarterly (every 3 months) Years 2-5.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01889381
|Contact: Jane Littleton, CRNP, MSNfirstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins University School of Medicine||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Carisa Cooney, MPH,CCRP 443-287-4629 email@example.com|
|Principal Investigator: W. P. Andrew Lee, MD|
|Sub-Investigator: Chad Gordon, DO|
|Sub-Investigator: Patrick Byrne, MD|
|Sub-Investigator: Gerald Brandacher, MD|
|Sub-Investigator: Steven Bonawitz, MD|
|Sub-Investigator: Amir Dorafshar, MD|
|Sub-Investigator: Damon Cooney, MD, PhD|
|Principal Investigator:||W. P. Andrew Lee, MD||Johns Hopkins University|