Human Penile Allotransplantation

NCT02395497 | Recruiting Phase 2 DMC

• 1 other identifier: NA_00089306
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amputation; Wounds and Injuries; Amputation, Traumatic; Urologic Surgical Procedures, Male; Amputation, Traumatic/Surgery; Penis/Transplantation; Penis/Surgery; Penis/Injuries; Congenital Anomaly, Male Genitalia

Keywords

Penile Transplant; Vascularized Composite Allotransplantation (VCA); Composite Tissue Allotransplantation (CTA); Penis; Amputation; Immunosuppression; Composite Tissue; Male; Humans; Allotransplantation; Micropenis; Severely Aambiguous Male Genitalia; congenital/birth defect

Outcome Measures

Primary Outcomes (1)

• Allograft Survival

  use an immunomodulatory protocol to reduce immunosuppression. Post-operative allograft survival will be assessed by various clinical measures including: physical assessments, imaging assessments (ultrasound, CT angiography, magnetic resonance (MR) Neurography and MRI) immune monitoring (screen patient sera for donor specific antibodies), hematologic and metabolic tests, viral tests, chimerism tests, and skin biopsies

  Transplantation through end of study period (up to 5 years)

Secondary Outcomes (9)

• Quality of Life (QOL) as assessed by Brief Symptom Inventory

  Transplantation through end of study period ( 5 years)

• QOL as assessed by Affect Balance Scale (ABS)

  Transplantation through end of study period (up to 5 years)

• QOL as assessed by NEO Five-Factor Inventory Scale (NEO-FFI)

  Transplantation through end of study period (up to 5 years)

• QOL as assessed by the International Index of Erectile Function (IIEF)

  Transplantation through end of study period (up to 5 years)

• Psychosexual Measures assessed by Self-Esteem and Relationship (SEAR) questionnaire

  Transplantation through end of study period ( 5 years)

Study Arms (1)

Treatment: Transplantation

EXPERIMENTAL

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.

Biological: Monoclonal Antibody (Humanized Anti-CD52); Drug: Tacrolimus; Procedure: Penile Allotransplantation

Interventions

Monoclonal Antibody (Humanized Anti-CD52) BIOLOGICAL

Treatment: Transplantation

Tacrolimus DRUG

Treatment: Transplantation

Penile Allotransplantation PROCEDURE

Treatment: Transplantation

Eligibility Criteria

• Age: 18 Years - 69 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged 16 - 65 years.
• Brain dead meeting the criteria for Determination of Death.
• Family consent for penile graft donation.
• Stable donor (i.e., does not require excessive vasopressors to maintain blood pressure).
• Same blood type as recipient.
• Negative lymphocytotoxic crossmatch.
• Accurately matched for skin tone
• Males of any race, color or ethnicity; aged 18-69 years.
• Recent (≥6 months) or remote (i.e., several decades) penile injury resulting in the loss of ≥75% of the phallus.
• Penectomy secondary to penile cancer
• Penile Cancer Survivors \> 5 years
• Micropenis associated with congenital/birth defect and severely ambiguous male genitalia
• Must have completed a clinic appointment with one of the study surgeons to discuss all penile reconstructive options.
• Completes the protocol informed consent form(s).
• No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of penile transplantation.).

You may not qualify if:

• Untreated sepsis.
• HIV (active or seropositive).
• Active tuberculosis.
• Active Hepatitis B infection.
• Hepatitis 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.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

RECRUITING

Related Publications (5)

• Schneeberger S, Gorantla VS, Brandacher G, Zeevi A, Demetris AJ, Lunz JG, Metes DM, Donnenberg AD, Shores JT, Dimartini AF, Kiss JE, Imbriglia JE, Azari K, Goitz RJ, Manders EK, Nguyen VT, Cooney DS, Wachtman GS, Keith JD, Fletcher DR, Macedo C, Planinsic R, Losee JE, Shapiro R, Starzl TE, Lee WP. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013 Feb;257(2):345-51. doi: 10.1097/SLA.0b013e31826d90bb.

  PMID: 23001085 BACKGROUND

• Bluebond-Langner R, Redett RJ. Phalloplasty in complete aphallia and ambiguous genitalia. Semin Plast Surg. 2011 Aug;25(3):196-205. doi: 10.1055/s-0031-1281489.

  PMID: 22851911 BACKGROUND

• Massanyi EZ, Gupta A, Goel S, Gearhart JP, Burnett AL, Bivalacqua TJ, Redett RJ. Radial forearm free flap phalloplasty for penile inadequacy in patients with exstrophy. J Urol. 2013 Oct;190(4 Suppl):1577-82. doi: 10.1016/j.juro.2012.12.050. Epub 2012 Dec 25.

  PMID: 23270911 BACKGROUND

• Tuffaha SH, Sacks JM, Shores JT, Brandacher G, Lee WPA, Cooney DS, Redett RJ. Using the dorsal, cavernosal, and external pudendal arteries for penile transplantation: technical considerations and perfusion territories. Plast Reconstr Surg. 2014 Jul;134(1):111e-119e. doi: 10.1097/PRS.0000000000000277.

  PMID: 24622570 BACKGROUND

• Schneeberger S, Landin L, Jableki J, Butler P, Hoehnke C, Brandacher G, Morelon E; ESOT CTA Working Group. Achievements and challenges in composite tissue allotransplantation. Transpl Int. 2011 Aug;24(8):760-9. doi: 10.1111/j.1432-2277.2011.01261.x. Epub 2011 May 9.

  PMID: 21554424 BACKGROUND

MeSH Terms

Conditions

Wounds and Injuries; Amputation, Traumatic; Congenital Abnormalities; Penis agenesis

Interventions

Antibodies, Monoclonal; Tacrolimus

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals

Study Officials

• Richard Redett, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jane Littleton, CRNP, MSN

CONTACT

410-955-6875; jlittl38@jhmi.edu

TBD TBD

CONTACT

443-287-7848

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 23, 2015
• Study Start: June 1, 2014
• Primary Completion (Estimated): June 1, 2034
• Study Completion (Estimated): June 1, 2039
• Last Updated: July 7, 2025

Record last verified: 2025-07

Locations

US (1)