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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to hand transplantation for individuals who have lost a hand or arm. It aims to make hand transplants safer by using the Pittsburgh Protocol, a special treatment plan that reduces the need for strong, long-term medications to prevent rejection of the new hand. The trial targets those who have lost a hand or arm below the shoulder and wish to regain function and appearance. Participants should not have certain medical conditions, such as untreated infections or active substance abuse issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 prior data suggests that this protocol is safe for hand transplantation?

Research has shown that hand transplants, when combined with a special treatment called the "Pittsburgh Protocol," yield promising safety results. This treatment uses bone marrow cells and just one drug to prevent the body from rejecting the new hand. Studies have found that this method is generally safe and well-tolerated, leading to successful transplant outcomes with less need for long-term medication.

In over 70 hand transplants worldwide, patients have often experienced good results in using their new hands. Traditional methods to prevent rejection required high doses of multiple drugs, which could cause serious side effects, such as infections and other health issues.

The Pittsburgh Protocol aims to use much lower doses of medication, potentially reducing these risks significantly. Early findings suggest that this new approach may offer a safer alternative, making hand transplants more accessible and less risky for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard options for hand loss from trauma, which typically involve prosthetics or multi-drug immunosuppression after transplantation, this treatment is unique because it uses a deceased donor hand transplant combined with a novel donor bone marrow cell therapy. This approach allows for single-drug immunosuppression, which reduces the risk of side effects associated with taking multiple drugs. Researchers are excited about this because the new protocol might make it possible to eventually wean patients off immunosuppression altogether, offering a more sustainable and less invasive long-term solution.

What evidence suggests that this trial's treatments could be effective for hand loss from trauma?

Research has shown that hand transplants can help individuals who have lost an upper limb regain movement and feeling. More than 70 successful hand transplants have demonstrated good functional results. This trial tests a new method called the Pittsburgh Protocol, which has proven effective in organ transplants. Participants will receive hand or arm transplantation combined with a novel donor bone marrow cell-based therapy, followed by single-drug immunosuppression. This approach aims to reduce the need for high doses of drugs that prevent rejection of the transplanted hand. Early results suggest this method could extend the transplant's longevity while reducing side effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Damon Cooney, MD, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01459107

NCT01459107 | Human Upper Extremity Allotransplantation Significance of Research: Hand transplantation could help upper extremity amputees ... Amputation, TraumaticWounds and InjuriesHand Injuries. Amputation, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12430936/

Successful forearm and hand transplantations from living ... ... traumatic amputation of the left arm at the proximal ... upper limb amputees by surgeons, particularly when prosthetic options are limited.

3. aetna.com aetna.com/cpb/medical/data/800_899/0816.html

Hand Transplantation - Medical Clinical Policy Bulletins Eligible participants are upper-limb amputees (below the elbow; regardless of when the amputation was performed) who are between the age of 18 and 55 years.

4. tandfonline.com tandfonline.com/doi/full/10.2147/TRRM.S94298

Full article: Hand transplantation: current challenges and ... Indications may include amputation of the dominant hand, bilateral amputations, distal amputations (less nerve regeneration required), and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7268554/

All hands on deck: Hand replantation versus transplantation ... data to encourage transplantation closer to the time of amputation when practicable. Avulsion and crush amputations result in worse outcomes than sharp ...

6. amjtransplant.org amjtransplant.org/article/S1600-6135(22)22327-2/fulltext

Hand transplantation in the United States: A review ... Data collection by the OPTN include wait list considerations, patient and graft survival, donor demographics, and safety and system parameters. Parameters ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522223272

Hand transplantation in the United States: A review of ... The purpose of this study was to review the current state of upper extremity transplantation in the United States contained in the OPTN database.