Human Upper Extremity Allotransplantation
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital, Orthopedic |
| Therapuetic Areas: | Orthopedics / Podiatry, Other |
| Healthy: | No |
| Age Range: | 18 - 69 |
| Updated: | 10/10/2018 |
| Start Date: | July 2011 |
| End Date: | June 2026 |
| Contact: | Jane Littleton, CRNP, MSN |
| Email: | jlittl38@jhmi.edu |
| Phone: | 410-955-6875 |
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.
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.
Inclusion Criteria:
- Recent (≥6 months) or remote (i.e., several decades) unilateral or bilateral upper
limb loss (below the shoulder) desiring limb transplantation.
- Below-shoulder amputation.
- Male or female and of any race, color or ethnicity.
- Aged 18-69 years.
- Completes the protocol informed consent form.
- No co-existing medical condition which, in the opinion of the study team, could affect
the immunomodulatory protocol, surgical procedure, or functional results (see Donor
and Recipient Exclusion Criteria below. If the condition is amenable to treatment, the
study team must agree that said condition should not significantly enhance the
surgical risks of upper extremity transplantation.)
- No co-existing psycho-social problems (i.e., alcoholism, drug abuse).
- Negative for malignancy for past 5 years.
- Negative for HIV at transplant.
- Negative crossmatch with donor.
- If female of child-bearing potential, negative serum pregnancy test.
- If female of child-bearing potential, consent to use reliable contraception for at
least one year following transplantation.
- Consents to bone marrow infusion as part of the treatment regime.
- USA citizen or equivalent.
- Patient agrees to comply with the protocol and states a dedication to the
immunomodulatory treatment regime.
Exclusion Criteria:
- Positive for any of the following conditions:
- Untreated sepsis.
- HIV (active or seropositive).
- Active tuberculosis.
- Hepatitis B or C.
- Viral encephalitis.
- Toxoplasmosis.
- Malignancy (within past 5 years).
- Current/recent (within 3 months of donation/screening consent) IV drug abuse.
- Paralysis of ischemic or traumatic origin.
- Inherited peripheral neuropathy.
- Infectious, post infectious, or inflammatory (axonal or demyelinating)
neuropathy.
- Toxic neuropathy (i.e. heavy metal poisoning, drug toxicity, industrial agent
exposure).
- Mixed connective tissue disease.
- Severe deforming rheumatoid or osteoarthritis in the limb.
- Type I (insulin-dependent) diabetes mellitus
- Conditions that, in the opinion of the study team, may impact the immunomodulatory
protocol potentially exposing the recipient to an unacceptable risk under
immunosuppressive treatment.
- Sensitized recipients with high levels (50%) of panel-reactive human leukocyte antigen
(HLA) antibodies.
- Conditions that may impact the success of the surgical procedure or increase the risk
of postoperative complications including inherited coagulopathies like Hemophilia,
Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thalassemias,
Sickle Cell disease, etc.
- Mixed connective tissue diseases and collagen diseases can result in poor wound
healing after surgery.
- Conditions that may impact functional outcomes including Lipopolysaccharidosis and
amyloidosis (may impact nerve regeneration) or rare disorders of bone healing like
osteopetrosis.
- Patients considered unsuitable per the consulted Psychiatrists appraisal.
We found this trial at
1
site
733 North Broadway
Baltimore, Maryland 21205
Baltimore, Maryland 21205
(410) 955-3182
Principal Investigator: W. P. Andrew Lee, MD
Phone: 443-287-4629
Johns Hopkins University School of Medicine Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is...
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