Human Upper Extremity Allotransplantation
Background: Millions of people each year sustain injuries, have tumors surgically removed, or are born with defects that require complex reconstructive surgeries to repair the problem. In case of hand, forearm, or arm amputation, prostheses only provide less than optimal motor function and do not enable sensory feedback. However, hand and arm transplantation is a means to restore the appearance, anatomy, and function of a native hand. Although over 65 hand transplants have been performed to date and good functional results have been achieved, widespread clinical use of this treatment has been limited due to adverse effects of life-long and high-dose immunosuppression needed to prevent graft rejection. These 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 hand 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 hand transplantation as a safe and effective reconstructive treatment for upper extremity amputations by minimizing maintenance immunosuppression therapy in unilateral and bilateral hand/forearm transplant patients. The investigators 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 (and perhaps elimination) of treatment. Although 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 30 human hand transplants employing this novel immunomodulatory protocol.
Specific Aims: 1) To establish hand transplantation as a safe and effective reconstructive strategy for the treatment of upper extremity amputations; 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: Hand transplantation could help upper extremity amputees recover functionality, self-esteem, and the capability to reintegrate into family and social life as "whole" individuals. The 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 widespread clinical application of hand transplantation. The significance of this research lies in combining the novel procedure of hand transplantation with the means of inducing partial tolerance to improve the safety, efficacy, and applicability of this reconstructive option.
Wounds and Injuries
Procedure: Deceased donor hand transplantation
Drug: Bone marrow cell-based therapy & single-drug immunosuppression.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Human Upper Extremity Allotransplantation|
- Graft Survival [ Time Frame: Transplantation through end of study period (up to 5 years) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||June 2021|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Transplantation)
Hand/arm transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning.
Procedure: Deceased donor hand transplantation
Deceased donor hand is surgically attached to recipient arm's stump.Drug: Bone marrow cell-based therapy & single-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 upper extremities 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.
|Contact: Cynthia Cohen, DNP,RN,CRNPfirstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins University School of Medicine||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Carisa M Cooney, MPH, CCRP 443-287-4629 email@example.com|
|Principal Investigator: W. P. Andrew Lee, MD|
|Sub-Investigator: Gerald Brandacher, MD|
|Sub-Investigator: Stefan Schneeberger, MD|
|Sub-Investigator: Damon S Cooney, MD, PhD|
|Sub-Investigator: Justin Sacks, MD|
|Principal Investigator:||W. P. Andrew Lee, MD||Johns Hopkins University|