Human Upper Extremity Transplantation

Study ID
STU 032011-081

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Kimberly Mackenzie
214-645-3261
kimberly.mackenzie@utsouthwestern.edu

Principal Investigator
Tae Chong

Summary

We propose to perform 10 human hand transplants utilizing standard immunosuppression protocols in use here at uT Southwestern Medical Center (kidney, heart, lung, liver). We expect to consent up to 75 potential subjects in order to accomplish 5 completed procedures. Patients will receive thymoglobulin induction with steroids followed by triple drug maintenance immunosuppression (prednisone, tacrolimus, and mycophenolate mofetil). The steroids will be weaned to a low dose within 3 months after transplantation. Postoperative care and recovery will consist of daily hand therapy, immune surveillance, protocol biopsies, and routine follow-up in the composite tissue transplant clinic. For the first year, the patient will participate in daily hand therapy with a certified hand therapist. Follow-up for surveillance biopsies of the transplant and to monitor immunosupppression will be scheduled monthly for the first year and annually thereafter for the duration of the transplant.

outcome Measures
This is a non-randomized subject self-controlled study, where the selection criteria and endpoints are not based on a calculated difference with regard to a control group, as only historical controls are available for comparison. Therefore, the investigators have defined the following two endpoints in order to address successful application of this protocol in hand transplant recipients.
1. Graft loss or severe damage: a patient who sustains graft loss for a reason that is not related to the surgery itself or suffers from severe graft damage due to uncontrolled rejection that is non-responsive to available drug/antibody therapy will be withdrawn from the study. a systematic analysis of the cause of graft loss or damage will then be performed.
2. Life threatening complications of immunosuppression: although the aim of this study is to implement a regimen that allows for minimization of maintenance immunosuppression, use of immunosuppressive agents cannot be entirely avoided. if complications secondary to the maintenance immunosuppressive regimen threaten to compromise the life of the patient, the drug treatment will be stopped, the graft amputated and the patient withdrawn from the study.

Participant Eligibility

Donor Selection Criteria
Brain dead donors who have met the criteria for Determination of Death will be selected by the hand transplant team in conjunction with the organ procurement agency (OPO) for Dallas x Southwest Transplant Alliance. The mandatory requirements are family consent for limb donation, stable donor (does not require excessive vasopressors to maintain blood pressure), age between 18 to 55 years, limb matched for size with recipient, same blood type as recipient, negative cross-match, and importantly accurately matched for gender, skin tone and race (may be relative requirement depending on recipient consent).

Recipient Selection Criteria Recipients will be selected from a population of subjects with bilateral upper limb loss. We expect the minimum selection/screening ratio for recipients to be 1:15. Recipients may be male or female and of any race, color or ethnicity. Inclusion criteria for the study:
1. Male or female, age (>18 years <60 years), of all races and ethnicities.
2. No serious co- existing medical (coronary artery disease, diabetes) or psycho-social problems (including alcoholism, drug abuse).
3. Must be negative for malignancy (for 10 years) or HIV (at transplant).
4. Negative crossmatch with donor.
5. Negative pregnancy test in female recipient of child bearing potential and consent to use reliable contraception for at least one year following transplantation.
6. Amputation must be at least 9-12 months ago. This is to allow tissue homeostasis to occur and to allow the individual time to adjust and cope with the injury. Moreover, they must have attempted prosthetic based rehabilitation and been unsatisfied with the level of independence and function provided by the prosthetic. Patients must have attempted the prosthetic for at least 3 months under the guidance of a certified prosthetist and occupational therapist. Level of amputation may be above or below the elbow.
7. Spanish-speaking subjects will be eligible for participation, as well as other non-English speaking subjects dependent on the availability of translators and translation services.