Limb Transplantation for Amputation

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must be taking: Immunosuppressants

Disqualifiers: Active malignancy, Mental instability, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores methods for successful limb transplants in individuals who have lost one or more limbs, aiming to enhance outcomes and quality of life. Participants will receive a limb from a deceased donor and must commit to extensive rehabilitation and take special medications to prevent rejection of the new limb. Ideal candidates have lost a dominant hand or multiple limbs between the wrist and shoulder or ankle and hip, have tried and struggled with prosthetics, and are prepared for a significant commitment to post-surgery care.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in limb transplantation.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be willing to take immunosuppressants for life, which might interact with other medications. It's best to discuss your current medications with the trial team.

What prior data suggests that limb transplantation is safe for patients with amputations?

Research has shown that limb transplants, such as hand transplants, carry certain risks. A key issue involves taking medication to prevent the body from rejecting the new limb. These medications can weaken the immune system, leading to serious side effects like infections or other health problems.

Studies have found that some patients experience complications, such as issues with blood vessels in the transplanted limb. In some cases, this has led to the removal of the transplanted limb. However, patient satisfaction often depends on the functionality of the new limb.

Overall, while limb transplants can greatly benefit amputees, managing these risks is crucial. Prospective trial participants should consider these factors and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Limb transplantation is unique because it offers the possibility of replacing a missing limb with a functional, living one, which is a significant shift from prosthetics, the current standard of care. Unlike prosthetics, which can be limited in functionality and sensation, limb transplants could potentially restore both movement and feeling, providing a more natural and integrated experience for the patient. Researchers are excited about this approach because it could dramatically improve quality of life, offering a level of rehabilitation that prosthetics simply can't match.

What evidence suggests that limb transplantation is effective for amputation?

Research has shown that limb transplantation, or VCA, can enhance life for those who have lost limbs. This trial will examine the effects of limb transplantation, with subjects undergoing single or multiple limb transplants. Studies indicate that success hinges on avoiding rejection of the new limb and restoring its function. Some patients encounter challenges, with about 17% requiring another amputation and 10.6% experiencing serious complications. However, advancements in techniques and patient care are making this option more promising. Overall, the goal is to help amputees move better and improve their daily lives. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 who have lost one or more limbs, from the wrist/ankle to just below the shoulder/hip, and haven't had success with prosthetics. They must be willing to undergo psychological evaluation, vaccinations, take lifelong immunosuppressants, commit to a minimum of two years of rehab post-transplant, and attend follow-up visits. Not eligible if they have active cancer risks or mental instability that affects treatment compliance.

Inclusion Criteria

I am willing to take drugs for life to prevent transplant rejection.

Willing to return for follow-up visits as determined by the treating physician.

My amputation is between my wrist and shoulder or ankle and hip, and it's functional.

Exclusion Criteria

I currently have cancer.

I have a condition that makes surgery or long-term immune suppression risky.

My cancer is at high risk of coming back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Several months

Multiple visits for psychiatric, social support evaluation, and imaging tests

Transplantation

Subjects will undergo single or multiple limb transplantation

Surgery and immediate recovery period

Inpatient hospital stay for surgery and initial recovery

Follow-up

Participants are monitored for safety and effectiveness after transplantation

18 months

Regular follow-up visits for monitoring and evaluation

Immune Suppression Optimization

Evaluation of the immune suppression protocol to prevent rejection

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Limb Transplantation

Trial Overview The study is testing limb transplantation from deceased donors to patients with amputations. It aims to develop best practices for this procedure in order to improve outcomes for those receiving multiple limb transplants.

How Is the Trial Designed?

Group I: Transplantation Experimental Treatment 1 Intervention

Subjects will undergo single or multiple limb transplantation

Limb Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Vascularized Composite Allotransplantation (VCA) for:

• Multiple extremity amputations
• Severe tissue defects
• Complex tissue injuries

Approved in European Union as Vascularized Composite Allotransplantation (VCA) for:

• Severe tissue defects
• Complex tissue injuries
• Facial reconstruction

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

From July 3, 2014, to February 28, 2018, 54 candidates were added to the OPTN VCA waiting list, with a notable increase in registrations following the introduction of uterine and penile transplants in the U.S.

Out of the candidates, 22 received deceased donor VCA transplants, but waiting times varied significantly, with some candidates receiving transplants quickly while others waited over 3 years, highlighting the need for further research into access and demand in VCA transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OPTN Vascularized Composite Allograft Waiting List: Current Status and Trends in the United States. Wainright, JL., Wholley, CL., Cherikh, WS., et al.[2019]

In a systematic review of 115 patients who underwent vascularized composite allotransplantation (VCA) for face and upper extremity reconstruction, the overall surgical complication rate was found to be 23%, highlighting the significant risks associated with this procedure.

The study revealed that 89% of patients experienced acute rejection, and 58% had opportunistic infections, indicating that while VCA can be beneficial for severe tissue loss, it carries a high risk of complications that must be carefully considered during patient selection and consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Reported Complications Related to Facial and Upper Extremity Vascularized Composite Allotransplantation. Milek, D., Reed, LT., Echternacht, SR., et al.[2023]

Vascularized composite allograft (VCA) transplants involve multiple tissues and are becoming more common, but there is limited data on their graft survival and infection risks.

VCA transplants have unique infection risk factors that differ from those associated with solid organ transplants, highlighting the need for tailored management strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications of vascularized composite allograft transplantation. Steinbrink, JM., Wolfe, CR.[2021]

Vascularized composite allotransplantation (VCA) involves complex transplants like hands and faces, and requires thorough psychosocial evaluations to ensure patient stability and support, as these factors significantly impact outcomes.

There is a need for standardized assessment tools to evaluate psychiatric health, social support, and quality of life in VCA patients, as nonadherence and psychosocial issues can lead to graft loss or decreased function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardizing psychosocial assessment for vascularized composite allotransplantation. Jowsey-Gregoire, S., Kumnig, M.[2018]

Vascularized composite allotransplantation (VCA) is an emerging area in reconstructive medicine that involves complex tissue types, including skin and bone marrow, which leads to unique immunological responses compared to traditional organ transplants.

The case report highlights a specific instance of trauma-induced rejection in an upper extremity transplant recipient, emphasizing the need for further research to understand rejection patterns in VCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trauma-induced Rejection in Vascularized Composite Allotransplantation. Etra, JW., Shores, JT., Sander, IB., et al.[2021]

Vascularized composite allotransplantation (VCA) is an effective procedure for restoring upper limb function in patients with acquired limb loss, particularly those who have undergone amputation due to trauma or severe sepsis.

Patients with amputations resulting from sepsis face unique challenges due to their history of global tissue hypoperfusion and multisystem organ failure, which must be considered when evaluating their candidacy for VCA and other transplant procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Nuances of Hand Transplantation After Sepsis. Zuo, KJ., Leonard, DA., Shores, JT., et al.[2023]

Vascularized composite tissue allotransplantation (VCA) has shown promising outcomes in upper extremity and facial transplants, but it also presents significant risks and complications that need to be carefully managed.

The review highlights the challenges in evaluating VCA outcomes due to the selective reporting of negative results, emphasizing the need for comprehensive data to improve patient consent and enhance overall graft and patient survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascularized Composite Allotransplantation: Medical Complications. Uluer, MC., Brazio, PS., Woodall, JD., et al.[2020]

In a study of 91 vascularized composite allotransplantation (VCA) procedures, a failure rate of 19.8% was observed, with significant failures linked to cases lacking psychological screening (56.3%) and competent social support systems (44%).

The findings highlight the need for improved perioperative risk management and ethical standards in VCA programs, particularly emphasizing the importance of psychological assessments and social support to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative risk factors for vascularized composite allotransplantation: a systematic review and proposal of identity-defining VCA. Zhu, H., Wei, X., Lineaweaver, W., et al.[2022]

Vascularized composite allotransplantation (VCA) is an innovative treatment for patients with limb loss or severe facial disfigurement, with 72 hand and 19 facial transplants performed globally.

While VCA can lead to good functional outcomes, it is complicated by skin rejection and requires long-term immunosuppression, highlighting the need for strategies to minimize immunosuppressive therapy to reduce associated risks and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial and hand allotransplantation. Pomahac, B., Gobble, RM., Schneeberger, S.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10350745/

Patient definitions of transplant success in upper extremity ... Participants rated their most important upper extremity vascularized composite allotransplantation outcomes as follows: not having transplant rejection, not ...

2. myast.org myast.org/vascularized-composite-allotransplantation-vca-research

Vascularized Composite Allotransplantation (VCA) Research This type of transplant is now known as Vascularized Composite ... Quality of life, social and economic outcomes including comparative effectiveness ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0003999325007208

Measuring Health-Related Quality of Life in Upper ... Objective. To develop patient-reported outcome (PRO) items tailored for upper extremity vascularized composite allotransplantation (UE VCA), a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4947978/

Composite Tissue Transplant of Hand or Arm - PubMed Central For various reasons, 17% of transplanted limbs were amputated, 6.4% of patients died within the first year after the transplant, and 10.6% of patients ...

5. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14132/full

Ex-Vivo Perfusion of Limb Vascularized Composite ... Within the past decade, use of EVMP in animal models and solid organ transplantation has made promising strides toward improved post-transplant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7756600/

Long‐term outcome after hand and forearm transplantation Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00711373

Vascularized Composite Allotransplantation of the Hand The major risk is the systemic immunosuppression that all current hand transplant recipients must take. As part of this clinical trial of hand transplanation we ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999325007208

Development of new patient-reported outcome items for ... These PRO items offer a structured way to measure HRQOL outcomes for UE VCA from the perspective of the recipients.

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK615569/

VCA Background Information and Context - NCBI Vascularized composite allotransplantation (VCA) replaces, in the recipient, vital tissue that has been severely damaged, rendered nonfunctional, or lost.

10. oaepublish.com oaepublish.com/articles/2347-9264.2021.116

lessons learned from hand transplantation and implications ... In this review, we discuss the ethical challenges of lower extremity VCA using available evidence for the upper extremity.