Penile Transplant for Traumatic Amputation

Overseen By TBD TBD

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Johns Hopkins University

Must be taking: Tacrolimus

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: Unknown

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since the study involves an immunomodulatory protocol, it's possible that adjustments to your medications might be necessary. It's best to discuss this with the study team.

What data supports the effectiveness of this treatment for penile transplantation?

Penile transplantation has shown promising results in restoring urinary function, natural erections, and sensation, with some successful cases reported. Long-term outcomes have been encouraging with proper immunosuppressive therapy, such as tacrolimus, which helps prevent rejection of the transplanted tissue. ^{1 2 3 4 5}

Is penile transplantation generally safe for humans?

Penile transplantation has been performed in a few cases worldwide, with mixed outcomes. While some long-term results are encouraging, such as stable kidney function and nerve regeneration, there are still uncertainties about long-term safety, including the risks of lifelong immunosuppression and potential complications. ^{1 2 3 4 6}

How is penile transplantation different from other treatments for traumatic amputation?

Penile transplantation is a unique treatment option for severe penile tissue loss, as it involves transplanting a donor penis to restore function and appearance, unlike traditional reconstructive surgeries. This procedure is not yet standard care and requires lifelong immunosuppression to prevent rejection, with tacrolimus being a key medication used to manage this. The treatment aims to provide better outcomes in terms of urinary function, natural erections, and sensation compared to existing options. ^{1 2 3 4 7}

What is the purpose of this trial?

Injuries to the genitalia are of concern to the military with emphasis placed on the surgical reconstruction and psychological health of these Wounded Warriors. However, despite significant surgical advances in microvascular surgery and autologous free tissue transfer, conventional reconstructions cannot truly replace the complicated structures and functions of the penis including the urethra, erogenous sensation, and erectile corporal bodies. Conventional reconstruction poses several challenges: patients may not have sufficient donor tissue due to other injuries or previous surgery; multiple operations are often needed to restore the neophallus; the final reconstruction only approximates the penis' native form; recreating the urethra is challenging and the new urethra is prone to stricture and fistula formation; the erectile function necessary for sexual intercourse is often lacking; and insufficient protective sensation can lead to penile implant extrusion, infection, subsequent explantation or loss of the reconstruction. The investigators propose this clinical trial to determine functional outcomes and quality of life for Wounded Warriors and civilians who choose to undergo penile allotransplantation. The investigators will combine extensive experience performing total penile reconstruction in a large population affected by congenital, traumatic, and therapeutically extirpated Genitourinary deformities and expertise in reconstructive transplantation using an immunomodulatory protocol to for this study. The investigators anticipate penile transplantation can potentially replace "like with like," restoring the appearance, anatomy, and function of the recipient in a manner far superior to autologous reconstruction. This project will establish the ability to perform penile allotransplantation using an immunomodulatory protocol and will compare outcomes with conventional phalloplasty patient results. Study Design: This is a non-randomized subject self-controlled clinical trial to implement a cell-based immunomodulatory protocol for penile allotransplantation. An intermediate deliverable is achieving allograft survival and functional return with reduced dosing/frequency of maintenance immunosuppression on steroid-free monotherapy (tacrolimus) immunosuppression. The long-term deliverable and goal is to demonstrate superior outcomes when compared to satisfaction and QOL in conventional phalloplasty patients 12-60 months post-transplant.

Research Team

Richard Redett, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for males aged 18-69 who have lost most of their penis due to injury or cancer. Donors must be brain-dead, a blood type match, stable without strong drugs to maintain blood pressure, and with family consent. Recipients should closely match the donor's skin tone.

Inclusion Criteria

My donor's blood pressure is stable without needing a lot of medication.

Donor: Brain dead meeting the criteria for Determination of Death

Donor: Family consent for penile graft donation

Exclusion Criteria

I have active tuberculosis.

I was diagnosed with cancer within the last 5 years.

I have paralysis due to a stroke or injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Penile transplantation with an immunomodulatory protocol consisting of monoclonal antibody induction therapy followed by donor bone marrow infusion and tacrolimus monotherapy

Immediate post-operative period

Follow-up

Participants are monitored for allograft survival and functional return with reduced dosing/frequency of maintenance immunosuppression

5 years

Long-term Follow-up

Assessment of quality of life and psychosexual measures using various questionnaires

12-60 months post-transplant

Treatment Details

Interventions

• Monoclonal Antibody
• Penile Allotransplantation
• Tacrolimus

Trial Overview The study tests penile allotransplantation using immunosuppression (tacrolimus) and humanized anti-CD52 antibodies. It aims to achieve graft survival with reduced immunosuppression and compare outcomes with traditional reconstructions in terms of function and quality of life.

Participant Groups

Group I: Treatment: Transplantation Experimental Treatment 3 Interventions

Penile transplantation with an immunomodulatory protocol consisting of monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

A novel ex vivo model demonstrated that rejection of penile tissue due to allogenic PBMC activation leads to impaired cavernous tissue physiology, characterized by cellular infiltration and apoptosis.

Cyclosporine A (CsA) effectively prevented rejection but did not enhance tissue relaxation, suggesting that other immunosuppressants like FK506 may be more beneficial for maintaining erectile function in penile transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology. Sopko, NA., Matsui, H., Lough, DM., et al.[2022]

Penile transplantation is a complex surgical procedure that has been successfully performed in three cases, with one patient achieving natural erections and the ability to impregnate his partner, demonstrating its potential for functional restoration.

Despite its success, the procedure poses significant ethical and psychosocial challenges, and there is still uncertainty regarding the effects of rejection and immunosuppression on graft function, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penile Allotransplantation for Complex Genitourinary Reconstruction. Sopko, NA., Tuffaha, SH., Lough, D., et al.[2022]

Penile transplantation has shown promise in restoring urinary function, natural erections, and sensation, but it is not yet considered standard care, and long-term outcomes remain uncertain.

The study proposes the Baltimore Criteria for an Ethical Approach to Penile Transplantation, emphasizing the need for clear guidelines and ethical considerations in this emerging field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Baltimore Criteria for an ethical approach to penile transplantation: a clinical guideline. Ngaage, LM., Elegbede, A., Sugarman, J., et al.[2021]

Long-term outcomes of penis transplants have been promising, particularly with proper compliance to immunosuppressive therapy, showing stable leukocyte counts and renal function up to 3 years post-transplant.

Continuous nerve regeneration in penile allografts has been observed for up to 3 years, indicating potential for functional recovery, although ethical and psychosocial considerations remain important for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons learned from the first 15 years of penile transplantation and updates to the Baltimore Criteria. Lopez, CD., Girard, AO., Lake, IV., et al.[2023]

The first successful penis transplant in the U.S. was performed on a patient who had undergone subtotal penectomy due to penile cancer, demonstrating the feasibility of this procedure for restoring anatomy and function.

Despite experiencing some complications, including rejection that required treatment, the patient reported significant improvements in self-image and health satisfaction, indicating the potential psychological benefits of penile transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penis Transplantation: First US Experience. Cetrulo, CL., Li, K., Salinas, HM., et al.[2022]

Penile transplantation, a complex surgical procedure involving vascularized composite allotransplantation, has been successfully performed in five cases worldwide, indicating its feasibility as a treatment option.

The procedure raises important ethical considerations regarding its aesthetic outcomes, potential complications, functional results, and cost compared to the less invasive alternative of phalloplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Penile Transplantation: An Unjustified Ethical Dilemma? Patel, HD.[2022]

Penile transplantation is being explored as a promising solution for patients with severe genital defects, particularly in cases of male genitourinary trauma, which is increasingly common in military settings.

The article highlights the limitations of traditional reconstructive methods and emphasizes the need for careful consideration of technical, logistical, and ethical factors to ensure successful outcomes in penile transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penile transplantation: an emerging option for genitourinary reconstruction. Tuffaha, SH., Cooney, DS., Sopko, NA., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology. [2022]

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

Penile Allotransplantation for Complex Genitourinary Reconstruction. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Baltimore Criteria for an ethical approach to penile transplantation: a clinical guideline. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Lessons learned from the first 15 years of penile transplantation and updates to the Baltimore Criteria. [2023]

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

Penis Transplantation: First US Experience. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Human Penile Transplantation: An Unjustified Ethical Dilemma? [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Penile transplantation: an emerging option for genitourinary reconstruction. [2022]