Human Penile Allotransplantation
Primary Purpose
Amputation, Wounds and Injuries, Amputation, Traumatic
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Monoclonal Antibody (Humanized Anti-CD52)
Tacrolimus
Penile Allotransplantation
Sponsored by
About this trial
This is an interventional treatment trial for Amputation focused on measuring Penile Transplant, Vascularized Composite Allotransplantation (VCA), Composite Tissue Allotransplantation (CTA), Penis, Amputation, Immunosuppression, Composite Tissue, Male, Humans, Allotransplantation, Micropenis, Severely Aambiguous Male Genitalia, congenital/birth defect
Eligibility Criteria
Donor Inclusion Criteria:
- Males aged 16 - 65 years.
- Brain dead meeting the criteria for Determination of Death.
- Family consent for penile graft donation.
- Stable donor (i.e., does not require excessive vasopressors to maintain blood pressure).
- Same blood type as recipient.
- Negative lymphocytotoxic crossmatch.
- Accurately matched for skin tone
Recipient Inclusion Criteria:
- Males of any race, color or ethnicity; aged 18-69 years.
- Recent (≥6 months) or remote (i.e., several decades) penile injury resulting in the loss of ≥75% of the phallus.
- Penectomy secondary to penile cancer
- Penile Cancer Survivors > 5 years
- Micropenis associated with congenital/birth defect and severely ambiguous male genitalia
- Must have completed a clinic appointment with one of the study surgeons to discuss all penile reconstructive options.
- Completes the protocol informed consent form(s).
- No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of penile transplantation.).
- No co-existing psycho-social problems (i.e., alcoholism, drug abuse).
- Negative for malignancy for past 5 years.
- Negative for HIV at transplant.
- Negative crossmatch with donor.
- Consents to sample (i.e., skin biopsy) collection and storage and bone marrow infusion as part of the treatment regimen.
- USA citizen or equivalent.
- Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regimen.
Recipient and Donor Exclusion Criteria:
- Untreated sepsis.
- HIV (active or seropositive).
- Active tuberculosis.
- Active Hepatitis B infection.
- Hepatitis C.
- Viral encephalitis.
- Toxoplasmosis.
- Malignancy (within past 5 years).
- Current/recent (within 3 months of donation/screening consent) IV drug abuse.
- Paralysis of ischemic or traumatic origin.
- Inherited peripheral neuropathy.
- Infectious, post infectious, or inflammatory (axonal or demyelinating) neuropathy.
- Toxic neuropathy (i.e. heavy metal poisoning, drug toxicity, industrial agent exposure).
- Mixed connective tissue disease.
- Severe deforming rheumatoid or osteoarthritis in the limb.
Donor Only Exclusion Criteria:
- Evidence of active herpes simplex virus-2 (HSV-2) infection.
- Tattoos: non-professional tattoo within the last 6 months, or personally identifiable tattoo (i.e., donor name) on potential transplant.
Recipient Only Exclusion Criteria:
- Conditions that, in the opinion of the study team, may impact the immunomodulatory protocol potentially exposing the recipient to an unacceptable risk under immunosuppressive treatment.
- Sensitized recipients with high levels (50%) of panel-reactive human leukocyte antigen (HLA) antibodies.
- Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thalassemias, Sickle Cell disease, etc.
- Conditions that may impact functional outcomes including Lipopolysaccharidosis and amyloidosis (may impact nerve regeneration).
- Patients considered psychologically/psychiatrically unsuitable.
Sites / Locations
- Johns Hopkins University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment: Transplantation
Arm Description
Penile transplantation with an immunomodulatory protocol consisting of monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
Outcomes
Primary Outcome Measures
Allograft Survival
use an immunomodulatory protocol to reduce immunosuppression. Post-operative allograft survival will be assessed by various clinical measures including: physical assessments, imaging assessments (ultrasound, CT angiography, magnetic resonance (MR) Neurography and MRI) immune monitoring (screen patient sera for donor specific antibodies), hematologic and metabolic tests, viral tests, chimerism tests, and skin biopsies
Secondary Outcome Measures
Quality of Life (QOL) as assessed by Brief Symptom Inventory
Brief Symptom Inventory questionnaire evaluates psychological distress and psychiatric disorders. It consists of 53-item self-report inventory in which participants rate the extent to which they have been bothered. 5-point rating scale, 0 indicating not at all bothered to 4 extremely bothered.
QOL as assessed by Affect Balance Scale (ABS)
ABS is a 10-item questionnaire that assess positive and negative affect as indicators of life satisfaction and/or well-being. Score range from 0-4. 0 indicating the feeling never affected to 4, where the feeling is affected always.
QOL as assessed by NEO Five-Factor Inventory Scale (NEO-FFI)
NEO-FFI is used to examine personality traits. Questions consists of 60 items. Items are scored from Strongly disagree to Strongly agreed
QOL as assessed by the International Index of Erectile Function (IIEF)
A score of 0-5 is awarded to each of the 15 questions that examine the 4 main domains of male sexual function: erectile function, orgasmic function, sexual desire and intercourse satisfaction.
Psychosexual Measures assessed by Self-Esteem and Relationship (SEAR) questionnaire
14 item questionnaire where responses are scored from 1-5. Response of 1 indicating almost never/never to 5 indicating almost always/always
T0 asses Erection Hardness Score (EHS)
EHS rates the hardness of erection on a scale of one to four, with four being the maximal score.
Modified Sexual Life Quality Questionnaire-Quality of Life (mSLQQ- QoL)
Used to validate as a tool for evaluating sexual QoL. mSLQQ is measured from score of 0 to 8. 0 indicates a low score compare to 8, indicating high. A score of 4 indicates, nothing has been changed.
Psychological Measures by Satisfaction with Life Scale (SWLS)
SWLS is a measure of life satisfaction. Uses scale to rate from 1-7, Where 1 indicates Strongly disagree to 7 indicating strongly agree.
Brief Pain Inventory (Short Form) ) (BPISF)
BPISF assesses the severity of pain and its impact on functioning. It is scored from 0 to 10, 0 indicating no pain, does not interfere to 10 indicating pain as bad as you can imagine, completely interferes.
Full Information
NCT ID
NCT02395497
First Posted
March 17, 2015
Last Updated
August 17, 2023
Sponsor
Johns Hopkins University
1. Study Identification
Unique Protocol Identification Number
NCT02395497
Brief Title
Human Penile Allotransplantation
Official Title
Human Penile Allotransplantation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 2014 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Injuries to the genitalia are of concern to the military with emphasis placed on the surgical reconstruction and psychological health of these Wounded Warriors. However, despite significant surgical advances in microvascular surgery and autologous free tissue transfer, conventional reconstructions cannot truly replace the complicated structures and functions of the penis including the urethra, erogenous sensation, and erectile corporal bodies. Conventional reconstruction poses several challenges: patients may not have sufficient donor tissue due to other injuries or previous surgery; multiple operations are often needed to restore the neophallus; the final reconstruction only approximates the penis' native form; recreating the urethra is challenging and the new urethra is prone to stricture and fistula formation; the erectile function necessary for sexual intercourse is often lacking; and insufficient protective sensation can lead to penile implant extrusion, infection, subsequent explantation or loss of the reconstruction.
The investigators propose this clinical trial to determine functional outcomes and quality of life for Wounded Warriors and civilians who choose to undergo penile allotransplantation. The investigators will combine extensive experience performing total penile reconstruction in a large population affected by congenital, traumatic, and therapeutically extirpated Genitourinary deformities and expertise in reconstructive transplantation using an immunomodulatory protocol to for this study. The investigators anticipate penile transplantation can potentially replace "like with like," restoring the appearance, anatomy, and function of the recipient in a manner far superior to autologous reconstruction. This project will establish the ability to perform penile allotransplantation using an immunomodulatory protocol and will compare outcomes with conventional phalloplasty patient results.
Study Design: This is a non-randomized subject self-controlled clinical trial to implement a cell-based immunomodulatory protocol for penile allotransplantation. An intermediate deliverable is achieving allograft survival and functional return with reduced dosing/frequency of maintenance immunosuppression on steroid-free monotherapy (tacrolimus) immunosuppression. The long-term deliverable and goal is to demonstrate superior outcomes when compared to satisfaction and QOL in conventional phalloplasty patients 12-60 months post-transplant.
Detailed Description
Specific Aims: 1) To assess the feasibility and function of penile allotransplantation in Wounded Warriors and civilians who have lost their penis due to battle or traumatic injury, using an immunomodulatory protocol to reduce immunosuppression; 2) To assess pre-to-post changes in QOL in patients who undergo penile allotransplantation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amputation, Wounds and Injuries, Amputation, Traumatic, Urologic Surgical Procedures, Male, Amputation, Traumatic/Surgery, Penis/Transplantation, Penis/Surgery, Penis/Injuries
Keywords
Penile Transplant, Vascularized Composite Allotransplantation (VCA), Composite Tissue Allotransplantation (CTA), Penis, Amputation, Immunosuppression, Composite Tissue, Male, Humans, Allotransplantation, Micropenis, Severely Aambiguous Male Genitalia, congenital/birth defect
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment: Transplantation
Arm Type
Experimental
Arm Description
Penile transplantation with an immunomodulatory protocol consisting of monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
Intervention Type
Biological
Intervention Name(s)
Monoclonal Antibody (Humanized Anti-CD52)
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Type
Procedure
Intervention Name(s)
Penile Allotransplantation
Primary Outcome Measure Information:
Title
Allograft Survival
Description
use an immunomodulatory protocol to reduce immunosuppression. Post-operative allograft survival will be assessed by various clinical measures including: physical assessments, imaging assessments (ultrasound, CT angiography, magnetic resonance (MR) Neurography and MRI) immune monitoring (screen patient sera for donor specific antibodies), hematologic and metabolic tests, viral tests, chimerism tests, and skin biopsies
Time Frame
Transplantation through end of study period (up to 5 years)
Secondary Outcome Measure Information:
Title
Quality of Life (QOL) as assessed by Brief Symptom Inventory
Description
Brief Symptom Inventory questionnaire evaluates psychological distress and psychiatric disorders. It consists of 53-item self-report inventory in which participants rate the extent to which they have been bothered. 5-point rating scale, 0 indicating not at all bothered to 4 extremely bothered.
Time Frame
Transplantation through end of study period ( 5 years)
Title
QOL as assessed by Affect Balance Scale (ABS)
Description
ABS is a 10-item questionnaire that assess positive and negative affect as indicators of life satisfaction and/or well-being. Score range from 0-4. 0 indicating the feeling never affected to 4, where the feeling is affected always.
Time Frame
Transplantation through end of study period (up to 5 years)
Title
QOL as assessed by NEO Five-Factor Inventory Scale (NEO-FFI)
Description
NEO-FFI is used to examine personality traits. Questions consists of 60 items. Items are scored from Strongly disagree to Strongly agreed
Time Frame
Transplantation through end of study period (up to 5 years)
Title
QOL as assessed by the International Index of Erectile Function (IIEF)
Description
A score of 0-5 is awarded to each of the 15 questions that examine the 4 main domains of male sexual function: erectile function, orgasmic function, sexual desire and intercourse satisfaction.
Time Frame
Transplantation through end of study period (up to 5 years)
Title
Psychosexual Measures assessed by Self-Esteem and Relationship (SEAR) questionnaire
Description
14 item questionnaire where responses are scored from 1-5. Response of 1 indicating almost never/never to 5 indicating almost always/always
Time Frame
Transplantation through end of study period ( 5 years)
Title
T0 asses Erection Hardness Score (EHS)
Description
EHS rates the hardness of erection on a scale of one to four, with four being the maximal score.
Time Frame
Transplantation through end of study period ( 5 years)
Title
Modified Sexual Life Quality Questionnaire-Quality of Life (mSLQQ- QoL)
Description
Used to validate as a tool for evaluating sexual QoL. mSLQQ is measured from score of 0 to 8. 0 indicates a low score compare to 8, indicating high. A score of 4 indicates, nothing has been changed.
Time Frame
Transplantation through end of study period ( 5 years)
Title
Psychological Measures by Satisfaction with Life Scale (SWLS)
Description
SWLS is a measure of life satisfaction. Uses scale to rate from 1-7, Where 1 indicates Strongly disagree to 7 indicating strongly agree.
Time Frame
Transplantation through end of study period ( 5 years)
Title
Brief Pain Inventory (Short Form) ) (BPISF)
Description
BPISF assesses the severity of pain and its impact on functioning. It is scored from 0 to 10, 0 indicating no pain, does not interfere to 10 indicating pain as bad as you can imagine, completely interferes.
Time Frame
Transplantation through end of study period ( 5 years)
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Donor Inclusion Criteria:
Males aged 16 - 65 years.
Brain dead meeting the criteria for Determination of Death.
Family consent for penile graft donation.
Stable donor (i.e., does not require excessive vasopressors to maintain blood pressure).
Same blood type as recipient.
Negative lymphocytotoxic crossmatch.
Accurately matched for skin tone
Recipient Inclusion Criteria:
Males of any race, color or ethnicity; aged 18-69 years.
Recent (≥6 months) or remote (i.e., several decades) penile injury resulting in the loss of ≥75% of the phallus.
Penectomy secondary to penile cancer
Penile Cancer Survivors > 5 years
Micropenis associated with congenital/birth defect and severely ambiguous male genitalia
Must have completed a clinic appointment with one of the study surgeons to discuss all penile reconstructive options.
Completes the protocol informed consent form(s).
No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of penile transplantation.).
No co-existing psycho-social problems (i.e., alcoholism, drug abuse).
Negative for malignancy for past 5 years.
Negative for HIV at transplant.
Negative crossmatch with donor.
Consents to sample (i.e., skin biopsy) collection and storage and bone marrow infusion as part of the treatment regimen.
USA citizen or equivalent.
Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regimen.
Recipient and Donor Exclusion Criteria:
Untreated sepsis.
HIV (active or seropositive).
Active tuberculosis.
Active Hepatitis B infection.
Hepatitis C.
Viral encephalitis.
Toxoplasmosis.
Malignancy (within past 5 years).
Current/recent (within 3 months of donation/screening consent) IV drug abuse.
Paralysis of ischemic or traumatic origin.
Inherited peripheral neuropathy.
Infectious, post infectious, or inflammatory (axonal or demyelinating) neuropathy.
Toxic neuropathy (i.e. heavy metal poisoning, drug toxicity, industrial agent exposure).
Mixed connective tissue disease.
Severe deforming rheumatoid or osteoarthritis in the limb.
Donor Only Exclusion Criteria:
Evidence of active herpes simplex virus-2 (HSV-2) infection.
Tattoos: non-professional tattoo within the last 6 months, or personally identifiable tattoo (i.e., donor name) on potential transplant.
Recipient Only Exclusion Criteria:
Conditions that, in the opinion of the study team, may impact the immunomodulatory protocol potentially exposing the recipient to an unacceptable risk under immunosuppressive treatment.
Sensitized recipients with high levels (50%) of panel-reactive human leukocyte antigen (HLA) antibodies.
Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thalassemias, Sickle Cell disease, etc.
Conditions that may impact functional outcomes including Lipopolysaccharidosis and amyloidosis (may impact nerve regeneration).
Patients considered psychologically/psychiatrically unsuitable.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jane Littleton, CRNP, MSN
Phone
410-955-6875
Email
jlittl38@jhmi.edu
First Name & Middle Initial & Last Name or Official Title & Degree
TBD TBD
Phone
443-287-7848
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Redett, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carisa Cooney, MPH,CCRP
Phone
443-287-4629
Email
ccooney3@jhmi.edu
First Name & Middle Initial & Last Name & Degree
TBD TBD
Phone
443-287-7848
First Name & Middle Initial & Last Name & Degree
Richard Redett, MD
First Name & Middle Initial & Last Name & Degree
Damon Cooney, MD,PHD
First Name & Middle Initial & Last Name & Degree
Gerald Brandacher, MD
First Name & Middle Initial & Last Name & Degree
Arthur Burnett, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
23001085
Citation
Schneeberger S, Gorantla VS, Brandacher G, Zeevi A, Demetris AJ, Lunz JG, Metes DM, Donnenberg AD, Shores JT, Dimartini AF, Kiss JE, Imbriglia JE, Azari K, Goitz RJ, Manders EK, Nguyen VT, Cooney DS, Wachtman GS, Keith JD, Fletcher DR, Macedo C, Planinsic R, Losee JE, Shapiro R, Starzl TE, Lee WP. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013 Feb;257(2):345-51. doi: 10.1097/SLA.0b013e31826d90bb.
Results Reference
background
PubMed Identifier
22851911
Citation
Bluebond-Langner R, Redett RJ. Phalloplasty in complete aphallia and ambiguous genitalia. Semin Plast Surg. 2011 Aug;25(3):196-205. doi: 10.1055/s-0031-1281489.
Results Reference
background
PubMed Identifier
23270911
Citation
Massanyi EZ, Gupta A, Goel S, Gearhart JP, Burnett AL, Bivalacqua TJ, Redett RJ. Radial forearm free flap phalloplasty for penile inadequacy in patients with exstrophy. J Urol. 2013 Oct;190(4 Suppl):1577-82. doi: 10.1016/j.juro.2012.12.050. Epub 2012 Dec 25.
Results Reference
background
PubMed Identifier
24622570
Citation
Tuffaha SH, Sacks JM, Shores JT, Brandacher G, Lee WPA, Cooney DS, Redett RJ. Using the dorsal, cavernosal, and external pudendal arteries for penile transplantation: technical considerations and perfusion territories. Plast Reconstr Surg. 2014 Jul;134(1):111e-119e. doi: 10.1097/PRS.0000000000000277.
Results Reference
background
PubMed Identifier
21554424
Citation
Schneeberger S, Landin L, Jableki J, Butler P, Hoehnke C, Brandacher G, Morelon E; ESOT CTA Working Group. Achievements and challenges in composite tissue allotransplantation. Transpl Int. 2011 Aug;24(8):760-9. doi: 10.1111/j.1432-2277.2011.01261.x. Epub 2011 May 9.
Results Reference
background
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Human Penile Allotransplantation
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