Human Upper Extremity (Hand and Forearm) Allotransplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by University of Pittsburgh
Sponsor:
Collaborators:
ARMED FORCES INSTITUTE OF REGENERATIVE MEDICINE (AFIRM)
U.S. Army Medical Research and Materiel Command
San Antonio Military Medical Center
Information provided by (Responsible Party):
Vijay Gorantla, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00722280
First received: July 23, 2008
Last updated: September 5, 2012
Last verified: September 2012
  Purpose

Overall Goal

To establish hand transplantation as a safe and effective reconstructive strategy for the treatment of upper extremity amputations.

Specific Aim

To reduce the risk of rejection and enable allograft survival while minimizing the requirement for long term high dose immunosuppression.

For this purpose, we propose to utilize the "Pittsburgh Protocol", which is an immunomodulatory strategy that has been implemented in solid organ transplants at UPMC. Early results in living related liver and kidney patients have confirmed that this protocol provides the means to allow graft survival with minimization of maintenance immunosuppression and even allows weaning of some patients from long-term immunosuppression.We hypothesize that a similar protocol can enable graft survival in highly immunogenic composite tissue allografts like hand transplants while reducing the number,dosing and/or frequency of immunosuppressive drugs associated with serious adverse effects.


Condition Intervention
Amputation, Traumatic
Procedure: Hand Transplantation

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Pittsburgh Protocol in Human Upper Extremity Allotransplantation

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Graft survival [ Time Frame: One to ten years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Functional Outcome [ Time Frame: One to ten years ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: December 2008
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hand Transplantation
Described above
Procedure: Hand Transplantation
This program is the primary site for a novel immune modulation protocol for hand and/or forearm transplantation using donor bone marrow stem cells. This protocol, otherwise called the "Pittsburgh Protocol" has been published and implemented in 8 hand/forearm transplantations. The Pittsburgh hand transplant program is the only center that has experience with the "Pittsburgh Protocol" to reduce the number and dosing of immunosuppressive drugs used to prevent rejection of hand/forearm transplants.
Other Names:
  • Induction Immunosuppression
  • Maintenance Immunosuppression
  • Surgical Transplantation of Human Hand or Forearm
  • Rehabilitation

Detailed Description:

Suitable candidates will be identified via patient information brochures and via advertisements directed at upper limb amputees. For this purpose, a web-page will be constructed for free access by interested individuals. This website will be accessible through standard search engines. Interested potential subjects will be instructed to contact the investigator for an appointment. At the time of appointment, candidates will be first requested to complete a screening consent form (SCF) before undergoing further evaluation/medical screening procedures. The SCF includes a written consent to obtain PHI of the candidate. When the candidate visits UPMC he will undergo a consultation with the PI who will perform a thorough clinical assessment and explain in detail the treatment options, risks and benefits of the procedure. Candidates will be requested to complete a screening consent at this stage. Appropriate subjects will then undergo further medical screening procedures that include a number of examinations and investigations to determine their candidacy for hand transplantation. Prospective recipients who are selected based on results of screening procedures will be invited to review and sign the full informed consent form prior to being wait-listed for the procedure.

The screening tests include:

History and physical exam, including height and weight Urine pregnancy test for all female subjects of childbearing potential Complete blood count, differential, reticulocyte count, platelet count ABO type Liver function tests including SGPT or SGOT, serum bilirubin (total and direct), total protein, albumin, alkaline phosphatase and GGT, PT, PTT with INR Serum electrolytes and renal function panel to include the following: sodium, potassium, chloride, carbon dioxide, calcium, phosphorus, magnesium, glucose, creatinine and BUN Urinalysis and creatinine clearance test to determine GFR Infectious disease studies: HIV antigen, HTLV I-II antibody, antibodies to HIV 1 and 2, hepatitis C virus, syphilis, hepatitis B core antibody, and hepatitis B surface antigen titers are required Infectious disease titers: CMV, EBV, HSV, toxoplasmosis and VZV (IgG and IgM when indicated) Pulmonary function tests, including DLCO2 Chest X-ray EKG and MUGA scan or echocardiogram for determination of cardiac ejection fraction Sinus X-ray (if clinically indicated) CT scans (CT Angiography)/MRI studies (Functional MRI, Skeletal MRIs of hand/hips) as indicated by medical history and physical examination Ophthalmologic examination Dental consult Psychiatric evaluation

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 CORE (Center for Organ Recovery and Education), the organ procurement agency (OPO) for Pittsburgh and covers Pennsylvania, New York and West Virginia. 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 upper limb loss. Recipients may be male or female and of any race, color or ethnicity. Inclusion criteria for the study: 1) Age (>18 years <60 years): Recipients <18 years of age are excluded due to limitations of giving full informed consent and the potentially increased risk of lymphoproliferative disorder in a younger population. Once hand transplantation and in particular the strategy for minimizing immunosuppression has proven to be efficacious and safe, the restrictions with regard to recipient age may be relaxed. 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) Consent to cell collection, storage, and bone marrow infusion as part of the treatment regime. 7) Amputation may be recent (acute injury) or remote (patient may have undergone rehabilitation with prostheses).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00722280

Contacts
Contact: Vijay Gorantla, MD, PhD 4126489677 gorantlavs@upmc.edu
Contact: Daniel E Foust, RN 4126572519 foustde@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Daniel E Foust, RN    412-657-2519    foustde@upmc.edu   
Contact: Vijay S Gorantla, MD, PhD    412-648-9677    gorantlavs@upmc.edu   
Principal Investigator: Vijay S Gorantla, MD, PhD         
Sponsors and Collaborators
University of Pittsburgh
ARMED FORCES INSTITUTE OF REGENERATIVE MEDICINE (AFIRM)
U.S. Army Medical Research and Materiel Command
San Antonio Military Medical Center
Investigators
Principal Investigator: Joseph E Losee, MD University of Pittsburgh
Study Director: Vijay S Gorantla, MD, PhD University of Pittsburgh
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vijay Gorantla, Administrative Medical Director, Pittsburgh Reconstructive Transplant Program, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00722280     History of Changes
Other Study ID Numbers: PRO07030180
Study First Received: July 23, 2008
Last Updated: September 5, 2012
Health Authority: USA: Institutional Review Board (IRB), University of Pittsburgh, USA
USA: Human Subject Research Review Board (HSRRB)
USA: Veterans Affairs Pittsburgh Healthcare System (VAPHS) IRB

Keywords provided by University of Pittsburgh:
Amputation, upper limb, composite tissue, immunosuppression

Additional relevant MeSH terms:
Amputation, Traumatic
Wounds and Injuries

ClinicalTrials.gov processed this record on August 20, 2014