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Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03240822
Recruitment Status : Recruiting
First Posted : August 7, 2017
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Tracking Information
First Submitted Date  ICMJE August 2, 2017
First Posted Date  ICMJE August 7, 2017
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE January 2017
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2017)
Need for Immunosuppressive drug therapy [ Time Frame: 6 months ]
The amount of immunosuppressive drug therapy will be recorded.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2017)
  • erectile function [ Time Frame: 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 [ Time Frame: 6 months ]
    This will be accomplished by penile biothesiometry
  • Determination of hemodynamic status [ Time Frame: 6 months ]
    Dynamic infusion pharmaco-cavernosometry and cavernosography will be utilized to better understand these changes
  • The Reintegration to Normal Living (RNL) Index [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma
Official Title  ICMJE Vascularized Composite Allotransplantation (VCA) for Devastating Penile and Concomitant Genital Trauma
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
All subjects receive transplant and immunosuppression therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Urologic Injuries
  • Genital Diseases, Male
  • Amputation
Intervention  ICMJE
  • Procedure: Penile Transplant
    Penile Allotransplantation
  • Biological: Monoclonal Antibody (Humanized Anti-CD52)
  • Drug: Tacrolimus
Study Arms  ICMJE 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.
Interventions:
  • Procedure: Penile Transplant
  • Biological: Monoclonal Antibody (Humanized Anti-CD52)
  • Drug: Tacrolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 4, 2017)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: This is a male, penile transplantation study.
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mary-Clare Day, RN BSN (336) 713-1343 mday@wakehealth.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03240822
Other Study ID Numbers  ICMJE IRB00027539
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Wake Forest University Health Sciences
Study Sponsor  ICMJE Wake Forest University Health Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anthony Atala, MD Professor
PRS Account Wake Forest University Health Sciences
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP