Human Upper Extremity (Hand and Forearm) Allotransplantation

October 15, 2018 updated by: Mario Solari, University of Pittsburgh

The Pittsburgh Protocol in Human Upper Extremity Allotransplantation

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

38

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Rehabilitation
  • Induction Immunosuppression
  • Maintenance Immunosuppression
  • Surgical Transplantation of Human Hand or Forearm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Graft survival
Time Frame: One to ten years
One to ten years

Secondary Outcome Measures

Outcome Measure
Time Frame
Functional Outcome
Time Frame: One to ten years
One to ten years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

U.S. Army Medical Research and Development Command
San Antonio Military Medical Center
Armed Forces Institute of Regenerative Medicine

Investigators

  • Principal Investigator: Joseph E Losee, MD, University of Pittsburgh Medical Center
  • Study Director: Vijay S Gorantla, MD, PhD, University of Pittsburgh Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (Actual)

October 1, 2017

Study Completion (Actual)

October 1, 2017

Study Registration Dates

First Submitted

July 23, 2008

First Submitted That Met QC Criteria

July 24, 2008

First Posted (Estimate)

July 25, 2008

Study Record Updates

Last Update Posted (Actual)

October 16, 2018

Last Update Submitted That Met QC Criteria

October 15, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO07030180

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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