Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03240822

Collaborator

(none)

Enrollment

Arm

107

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a 4-year, non-randomized, single center, patient self-controlled, clinical trial (though enrolled subjects will be followed for life as are all transplant patients) for patients seeking allotransplantation of the male external genitalia (MEG), or penile tissue, as a feasible reconstructive strategy for the treatment of devastating and irreversible injuries to the genitalia. In addition to receiving penile allotransplantation and post-operative monitoring and support, enrolled patients will receive an innovative and clinically proven immunomodulatory protocol that combines lymphocyte depletion of the recipient with donor bone marrow cell infusion. Patients will be treated with lymphocyte depleting induction therapy, donor bone marrow cell infusion and tacrolimus. After the first year, maintenance immunosuppression will be modified gradually and cautiously (tapered dose reduction or spaced frequency dosing of tacrolimus) in selected patients based on a critical evaluation of clinical and immunologic outcomes. Outcomes will include but not be limited to functional metrics (sensation, erection, voiding), psychosocial (body integrity, adaptation to transplant) and health related quality of life (HRQOL) measures.

Condition or Disease	Intervention/Treatment	Phase
Urologic Injuries Genital Diseases, Male Amputation	Procedure: Penile Transplant Biological: Monoclonal Antibody (Humanized Anti-CD52) Drug: Tacrolimus	Phase 1

Detailed Description

Initial treatment with an antibody targeting recipient immune cells followed by triple-drug maintenance therapy represents the current standard in clinical VCA. Our protocol is different from the existing conventional drug treatments used in MEG allotransplantation in that it combines donor bone marrow infusion with an immunosuppression sparing protocol. The primary goal of this pilot clinical trial is to determine the feasibility of using allogeneic penile tissue to repair/replace irreversibly damaged external genitalia. Enrolled and transplanted subjects will be followed for their lifetime as a transplant patient.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

All subjects receive transplant and immunosuppression therapyAll subjects receive transplant and immunosuppression therapy

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Vascularized Composite Allotransplantation (VCA) for Devastating Penile and Concomitant Genital Trauma

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Penile Allotransplant and Immunosuppression Treatment Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.	Procedure: Penile Transplant Penile Allotransplantation Biological: Monoclonal Antibody (Humanized Anti-CD52) Drug: Tacrolimus

Arm

Intervention/Treatment

Experimental: Penile Allotransplant and Immunosuppression Treatment

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

Procedure: Penile Transplant

Penile Allotransplantation

Biological: Monoclonal Antibody (Humanized Anti-CD52)

Drug: Tacrolimus

Outcome Measures

Primary Outcome Measures

Need for Immunosuppressive drug therapy [6 months]
The amount of immunosuppressive drug therapy will be recorded.

Secondary Outcome Measures

erectile function [6 months]
This will be assessed following intracorporal injection of vaso-active agents, such as prostaglandin, phentolamine, papaverine, or some mixture of these drugs (i.e. Trimix). and through high-resolution duplex Doppler ultrasonography
Assessment of sensory return and sensory thresholds [6 months]
This will be accomplished by penile biothesiometry
Determination of hemodynamic status [6 months]
Dynamic infusion pharmaco-cavernosometry and cavernosography will be utilized to better understand these changes
The Reintegration to Normal Living (RNL) Index [6 months]
The RNL is an 11-item questionnaire that asks how a person manages activities, roles, and relationships on a day-to-day basis.
The Situational Inventory of Body-Image Dysphoria (SIBID) [6 months]
The SIBID is a multidimensional body-image survey assessment of people's negative body-image emotions in everyday situations and physical experiences.
The Function and Body Image Survey [6 months]
This survey consists of six open-ended questions regarding personal thoughts, opinions, and experiences about the transplant, and the individual's current functional abilities.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria: For Recipients

Male
18-40 years
Irreversible and devastating genitalia damage not amenable to conventional reconstruction.
Patent main vessels leading into the remaining penile stump, as confirmed by angiography.
Adequate penile stump (> 2.5cm) to facilitate placement of a tourniquet, debridement of the distal portion and sufficient distal mobilization of the structures requiring anastomosis
Eligible for long term standard of care coverage

Exclusion Criteria: For Recipients

Documented history of:
cancer
renal impairment
hepatic disorders
neurologic disorders (sensory or motor function deficits)
severe scarring with poor host tissue bed
penile resection or implant surgery
diabetes
hypertension
hyperlipidemia
coronary artery disease
untreated genital cancer
HIV, Hepatitis B or C, or any infectious disease
erectile dysfunction
Peyronie's disease
urethral stricture disease
balanitis
xerotica obliterans
pelvic embolization
pelvic radiation
untreated hypogonadism
prior prostate surgery
recurrent urinary tract infections (UTIs)
nephrolithiasis
connective tissue disease or collagen disease
lipopolysaccharidosis or amyloidosis
Use of 5-alpha-reductase inhibitors
External signs, sequelae or positive serology of sexually transmitted disease (including HPV)
Active UTI, stones, urethral edema and other pathology that prevents urethral anastomosis
Current or past substance abuse
Current or past smoker (within past 3 months)
Use of any medications known to cause vasoconstriction
Psychiatric illness or psychological problems, or deemed unsuitable on psychiatric evaluation
Any condition that may prevent transplantation (positive cross match, high panel reactive antibody (PRA), etc.)
Uncontrolled bleeding disorder, platelet count > 50,000, hemophilia or any other inherited coagulopathy or need to routinely receive blood products for bleeding disorders
Concurrent participation in any other clinical investigation during the period of this investigation
Inability to undergo leukapheresis
Inability to participate in all necessary study activities due to physical or mental limitations
Inability or unwillingness to return for all required follow-up visits.
Inability or unwillingness to sign the patient informed consent document.