Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma

Amputation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03240822
• Other study ID #: IRB00027539
• Status: Withdrawn
• Phase: Phase 1
• Start date: January 2017
• Est. completion date: December 2025

Study information

• Verified date: July 2020
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2025
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amputation
• Genital Diseases, Male
• Urologic Injuries
• Wounds and Injuries

Intervention

Procedure:
• Penile Transplant
Penile Allotransplantation

Biological:
• Monoclonal Antibody (Humanized Anti-CD52)

Drug:
• Tacrolimus

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Need for Immunosuppressive drug therapy	The amount of immunosuppressive drug therapy will be recorded.	6 months
Secondary	erectile function	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	6 months
Secondary	Assessment of sensory return and sensory thresholds	This will be accomplished by penile biothesiometry	6 months
Secondary	Determination of hemodynamic status	Dynamic infusion pharmaco-cavernosometry and cavernosography will be utilized to better understand these changes	6 months
Secondary	The Reintegration to Normal Living (RNL) Index	The RNL is an 11-item questionnaire that asks how a person manages activities, roles, and relationships on a day-to-day basis.	6 months
Secondary	The Situational Inventory of Body-Image Dysphoria (SIBID)	The SIBID is a multidimensional body-image survey assessment of people's negative body-image emotions in everyday situations and physical experiences.	6 months
Secondary	The Function and Body Image Survey	This survey consists of six open-ended questions regarding personal thoughts, opinions, and experiences about the transplant, and the individual's current functional abilities.	6 months