Human Upper Extremity Allotransplantation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01459107|
Recruitment Status : Recruiting
First Posted : October 25, 2011
Last Update Posted : May 13, 2021
Background: Millions of people each year sustain injuries, have tumors surgically removed, or are born with defects that require complex reconstructive surgeries to repair. In the case of hand, forearm, or arm amputation, prostheses only provide less than optimal motor function and no sensory feedback. However, hand and arm transplantation is a means to restore the appearance, anatomy, and function of a native hand. Although over 70 hand transplants have been performed to date and good functional results have been achieved, widespread clinical use has been limited due to 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 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. 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 30 human hand transplants employing this novel 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.
|Condition or disease||Intervention/treatment||Phase|
|Amputation, Traumatic Wounds and Injuries Hand Injuries||Procedure: Deceased donor hand transplantation Drug: Bone marrow cell-based therapy & single-drug immunosuppression.||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Human Upper Extremity Allotransplantation|
|Actual Study Start Date :||July 2011|
|Estimated Primary Completion Date :||June 2026|
|Estimated Study Completion Date :||June 2026|
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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01459107
|Contact: Jane Littleton, CRNP, MSNfirstname.lastname@example.org|
|Contact: TBD TBD||443-287-7848|
|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|
|Contact: TBD TBD 443-287-7848|
|Principal Investigator: Jaimie Shores, MD|
|Sub-Investigator: Gerald Brandacher, MD|
|Sub-Investigator: Damon S Cooney, MD, PhD|
|Principal Investigator:||Jaimie Shores, MD||Johns Hopkins University|