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Human Upper Extremity (Hand and Forearm) 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. Read our disclaimer for details. Identifier: NCT00722280
Recruitment Status : Terminated (loss of funding)
First Posted : July 25, 2008
Last Update Posted : October 16, 2018
Armed Forces Institute of Regenerative Medicine
U.S. Army Medical Research and Development Command
San Antonio Military Medical Center
Information provided by (Responsible Party):
Mario Solari, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE July 23, 2008
First Posted Date  ICMJE July 25, 2008
Last Update Posted Date October 16, 2018
Study Start Date  ICMJE December 2008
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2008)
Graft survival [ Time Frame: One to ten years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00722280 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2008)
Functional Outcome [ Time Frame: One to ten years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Human Upper Extremity (Hand and Forearm) Allotransplantation
Official Title  ICMJE The Pittsburgh Protocol in Human Upper Extremity Allotransplantation
Brief Summary

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.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Amputation, Traumatic
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Hand Transplantation
Described above
Intervention: Procedure: Hand Transplantation
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 23, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2008)
Actual Study Completion Date  ICMJE October 2017
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  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).

Exclusion Criteria:

  1. Conditions that may impact the immunomodulatory protocol: These include diseases like HIV or malignancy that could expose the recipient to an unacceptable risk under immunosuppressive treatment. Sensitized recipients with high level of preformed antibodies are also at risk.
  2. Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications: These include inherited coagulopathies like Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thallassemias, Sickle Cell disease etc. Mixed connective tissue diseases and collagen diseases can result in poor wound healing after surgery,
  3. Conditions that may impact functional outcomes: Lipopolysaccharidoses and amyloidosis are few of the conditions that may impact nerve regeneration and impair outcomes. Also, rare disorders of bone healing like osteopetrosis may also be causes for exclusion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00722280
Other Study ID Numbers  ICMJE PRO07030180
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mario Solari, University of Pittsburgh
Study Sponsor  ICMJE University of Pittsburgh
Collaborators  ICMJE
  • Armed Forces Institute of Regenerative Medicine
  • U.S. Army Medical Research and Development Command
  • San Antonio Military Medical Center
Investigators  ICMJE
Principal Investigator: Joseph E Losee, MD University of Pittsburgh Medical Center
Study Director: Vijay S Gorantla, MD, PhD University of Pittsburgh Medical Center
PRS Account University of Pittsburgh
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP