Amputation, Genital Diseases, Male, Urologic Injuries
Conditions
Keywords
Penile Trauma, Allotransplantation, Vascularized Composite Allotransplantation, VCA, Genital Trauma, Penile Transplantation, Amputation, Penile Injury
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.
Interventions
PROCEDUREPenile Transplant
Penile Allotransplantation
DRUGTacrolimus
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects receive transplant and immunosuppression therapy
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Need for Immunosuppressive drug therapy | 6 months | The amount of immunosuppressive drug therapy will be recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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. |
Outcome results
None listed