Clinical trial NCT03240822: Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma
Official title: Vascularized Composite Allotransplantation (VCA) for Devastating Penile and Concomitant Genital Trauma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Urologic Injuries
Genital Diseases, Male
Amputation
Keywords: Penile Trauma
Allotransplantation
Vascularized Composite Allotransplantation
VCA
Genital Trauma
Penile Transplantation
Amputation
Penile Injury
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2017-08-07
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All subjects receive transplant and immunosuppression therapy
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria: For Recipients

1. Male
2. 18-40 years
3. Irreversible and devastating genitalia damage not amenable to conventional reconstruction.
4. Patent main vessels leading into the remaining penile stump, as confirmed by angiography.
5. 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
6. Eligible for long term standard of care coverage

Exclusion Criteria: For Recipients

1. Documented history of:

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

Primary outcomes:
measure: Need for Immunosuppressive drug therapy
timeFrame: 6 months
Secondary outcomes:
measure: erectile function
timeFrame: 6 months
measure: Assessment of sensory return and sensory thresholds
timeFrame: 6 months
measure: Determination of hemodynamic status
timeFrame: 6 months
measure: The Reintegration to Normal Living (RNL) Index
timeFrame: 6 months
measure: The Situational Inventory of Body-Image Dysphoria (SIBID)
timeFrame: 6 months
measure: The Function and Body Image Survey
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Professor
name: Anthony Atala, MD
role: PRINCIPAL_INVESTIGATOR
References: