Hand Transplant for Hand Loss from Trauma

Overseen By TBD TBD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must be taking: Immunosuppressants

Disqualifiers: Diabetes, HIV, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the hand transplant trial?

The trial information does not specify if you need to stop your current medications. However, since the trial involves immunosuppressive treatment, it's possible that some medications might need to be adjusted. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Deceased Donor Hand Transplantation for hand loss from trauma?

Hand transplantation has shown promising results, with 100% patient survival and graft survival at 1 and 2 years, and most patients achieving protective and discriminative sensation, allowing them to perform daily activities and return to work. Additionally, 15 recipients reported an improved quality of life, highlighting the potential benefits of this treatment. ^{1 2 3 4 5}

Is hand transplantation safe for humans?

Hand transplantation has been shown to be generally safe in humans, with no life-threatening complications or cancers reported. However, patients need to take lifelong immunosuppressive drugs, which can have serious side effects, and there is a risk of rejection if the medication is not taken as prescribed. ^{1 2 3 4 6}

How is the Pittsburgh Protocol treatment for hand transplantation unique?

The Pittsburgh Protocol for hand transplantation is unique because it aims to minimize the use of multiple immunosuppressive drugs, which are typically required for life to prevent rejection of the transplanted hand. This approach focuses on using a single-drug immunosuppression strategy, potentially reducing the risk of serious side effects associated with long-term use of multiple immunosuppressive medications. ^{1 5 6 7 8}

Research Team

Damon Cooney, MD, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-69 who've lost a hand, forearm, or arm and want to undergo transplantation. They must be in good health without conditions that could interfere with the treatment, willing to follow the protocol including bone marrow infusion, and able to pay for care if not a US citizen. Women of childbearing age should agree to use contraception.

Inclusion Criteria

I have had an amputation below the shoulder.

Completes the protocol informed consent form

No co-existing psycho-social problems

Exclusion Criteria

I have not been treated for sepsis, HIV, active TB, Hepatitis B or C, viral encephalitis, toxoplasmosis, or any cancer in the last 5 years.

I do not have a history of drug abuse, paralysis, inherited neuropathy, or severe arthritis.

I have Type 1 diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Hand/arm transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning

Initial surgery and immediate post-operative period

Daily visits Days 1-28

Post-operative Monitoring

Monitoring of graft survival and immunosuppression levels

5 years

Semiweekly Weeks 5-12, weekly Weeks 13-25, biweekly Weeks 26-38, monthly Months 10-12, quarterly Years 2-5

Follow-up

Participants are monitored for long-term safety and effectiveness after transplantation

Up to 5 years

Treatment Details

Interventions

• Deceased Donor Hand Transplantation
• Pittsburgh Protocol
• Single-Drug Immunosuppression

Trial Overview The study tests a new approach combining bone marrow cell therapy with low-dose immunosuppression (Pittsburgh Protocol) in hand transplants from deceased donors. The goal is safer and more effective limb restoration by reducing long-term high-dose medication needs after transplanting hands/forearms.

Participant Groups

Group I: Treatment (Transplantation) Experimental Treatment 2 Interventions

Hand/arm transplantation in combination with a novel donor bone marrow cell-based therapy followed by single-drug immunosuppression with potential weaning.

Deceased Donor Hand Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Hand Transplantation for:

• Upper extremity amputations
• Severe hand deformities

Approved in European Union as Hand Transplantation for:

• Upper extremity amputations
• Severe hand deformities

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Armed Forces Institute of Regenerative Medicine

Collaborator

Trials

7

Recruited

220+

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Findings from Research

Hand transplantation has evolved significantly over the past decade, showing promising immunological and functional outcomes, but the need for lifelong immunosuppression remains a major challenge due to potential side effects.

Recent advancements in immunosuppressive drugs and innovative cell-based therapies are demonstrating success in reducing the need for immunosuppressive medication and promoting tolerance, which could improve the overall safety and effectiveness of hand transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimizing immunosuppression in hand transplantation. Brandacher, G., Lee, WP., Schneeberger, S.[2022]

A new immunomodulatory protocol for hand transplantation, which includes donor bone marrow infusion and low-dose tacrolimus, has been successfully applied in clinical settings, leading to good-to-excellent functional recovery in patients.

This approach allows for a favorable risk-benefit balance by minimizing immunosuppression while still enabling transplant recipients to regain autonomy and productivity in their lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation. Lee, WPA., Shores, JT., Brandacher, G.[2022]

In a study involving two recipients of bilateral hand allografts, sirolimus-based immunosuppressive therapy did not delay bone healing or cause nonunion after joint surgeries, indicating its safety in this context.

Both recipients showed improved functionality in daily activities following the transplant and subsequent joint surgeries, suggesting that sirolimus does not hinder recovery in upper limb reconstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone healing after secondary surgery on hand allografts under sirolimus-based maintenance immunosuppression. Cavadas, PC., Hernan, I., Landin, L., et al.[2013]

In a review of 24 hand transplantations performed on 18 male patients, both patient and graft survival rates were 100% at 1 and 2 years, highlighting the efficacy of the immunosuppressive therapy used, which included tacrolimus and mycophenolate mofetil.

Despite some cases of acute rejection, all compliant patients experienced reversible rejection episodes, and 90% of recipients returned to work, indicating significant improvements in quality of life and functional recovery after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation. Lanzetta, M., Petruzzo, P., Dubernard, JM., et al.[2021]

Hand transplantation is a viable option for select patients with traumatic upper extremity amputations, with 72 hands successfully transplanted in 51 patients worldwide since 1998.

A major challenge in hand transplantation is the need for lifelong immunosuppression to prevent rejection, particularly of the skin, which is the most vulnerable tissue; ongoing research aims to minimize this immunosuppression to improve the procedure's applicability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hand transplantation - fiction or reality?]. Vögelin, E.[2013]

The first double hand transplantation using a conventional immunosuppressive protocol was successful in a 33-year-old man, demonstrating both safety and efficacy over a two-year follow-up period.

Despite two episodes of acute rejection, which were effectively managed, the patient experienced no serious complications such as infections or malignancies, indicating that the immunosuppressive regimen was well-tolerated and effective for graft survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. Petruzzo, P., Revillard, JP., Kanitakis, J., et al.[2019]

Recent advances in transplant immunology are enabling the possibility of composite tissue allotransplantation with less potent immunosuppressive regimens, which could improve patient outcomes.

Hand transplantation has been the most common type of composite tissue allotransplantation, with over 50 procedures performed globally, highlighting its growing acceptance and potential in enhancing quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Composite tissue allotransplantation: hand transplantation and beyond. Shores, JT., Brandacher, G., Schneeberger, S., et al.[2022]

Hand transplantation shows promising functional results, with six patients in this study recovering protective and some discriminative sensation in their transplanted hands, indicating better outcomes compared to prosthetic options.

The study involved a well-defined immunosuppressive protocol and reported no surgical complications, although all patients experienced skin rejection at an average of 40 days post-surgery, highlighting the importance of adherence to immunosuppressive therapy to prevent rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human hand transplantation: what have we learned? Lanzetta, M., Petruzzo, P., Vitale, G., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Minimizing immunosuppression in hand transplantation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Bone healing after secondary surgery on hand allografts under sirolimus-based maintenance immunosuppression. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[Hand transplantation - fiction or reality?]. [2013]

6. Denmark pubmed.ncbi.nlm.nih.gov

First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Composite tissue allotransplantation: hand transplantation and beyond. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Human hand transplantation: what have we learned? [2013]