Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasms

Nervous System Diseases

Death

Renal Insufficiency

Urinary Bladder Neoplasms

Urinary Bladder Diseases

Urinary Bladder, Neurogenic

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Male Urogenital Diseases

Kidney Diseases

Neurologic Manifestations

Patients with terminal bladders who do not have kidney failure and who qualify for the study may undergo bladder transplantation.

Patients with terminal bladders who also have kidney failure and who qualify for the study may undergo combined kidney and bladder transplantation.

A bladder transplantation will be performed. The bladder will be recovered from a brain-dead human donor. The connections that will be made will include connections between donor and recipient blood vessels, the bladder transplant and the recipient urethra, and the recipient's ureter(s) to the new bladder.

Bladder Transplantation

For patients who qualify for a combined kidney and bladder transplant, both a kidney and a bladder transplant will be performed. Both kidney and bladder allografts will be recovered from the same brain-dead human donor. The connections that will be made will include connections between donor and recipient blood vessels, the bladder transplant and the recipient urethra, and the kidney transplant ureter to the transplanted bladder. If the recipient has continued urine output, new connections between the native ureters and the transplanted bladder will also be made.

Combined Kidney and Bladder Transplantation

Dana Lopez, MPH

Gina Choi

Magdalena Mendez-Smith

Nima Nassiri, MD

The goal of this clinical trial is to demonstrate the feasibility of bladder transplantation in patients with terminal bladder diseases who would benefit from a new bladder or a combined kidney and bladder transplant. The main questions it aims to answer are:

* Is human bladder transplantation feasible and safe?
* How will the new bladder function in terms of storage and emptying?

Participants will undergo a bladder-only or combined kidney and bladder transplantation. They will then be followed for two years to evaluate the efficacy, safety, and functionality of the bladder transplant.

Deceased Donor Bladder or Combined Kidney-bladder Transplantation: a Phase 0 First-in-human Study

Vascularized Composite Bladder Allograft Transplantation: a Phase 0 (First-in-human) Study for Deceased Donor Bladder or Combined Kidney-bladder Transplantation

The technical success of bladder transplantation will be evaluated. Technical success is defined as sustained and adequate perfusion to the bladder to maintain viability, as assessed through cystoscopic visual inspection and imaging, including ultrasound and cross-sectional imaging.

Adverse events will be evaluated. The endpoint for this outcome will be immediate peri-operative, 30, and 90-day adverse profiles. CTCAE v5 criteria will be used to describe adverse events. Of note a rejection episode managed medically will be defined as a grade 3 adverse event, while rejection requiring allograft explantation will be graded as a CTCAE grade 4 event.

Monitoring for immune or cell-mediated rejection will be monitored for the duration of the study. The endpoint for this outcome will be the incidence of acute (within 7 days) and delayed transplant rejection (up to 30 days) post-transplantation. Rejection will be graded using a modified histological grading system adapted from Banff criteria, similar to that adopted in uterine transplantation. This is adapted from pre-existing grading criteria for vascularized composite allograft rejection. Chronic rejection will be evaluated thereafter, up to 1 year at regular follow-up intervals.

The capacity of the bladder will be measured by ultrasound and cystoscopic visualization at 3 month intervals during the first year post-transplant, and as clinically indicated thereafter. The ability of the bladder to empty will be evaluated through using uroflowmetry studies at 3 month intervals and urodynamic evaluations. Successful bladder capacity is defined as a volume exceeding 300 cc, while successful bladder emptying will be defined by a post-void residual of less than 100 cc.

Spots Global Cancer Trial Database for vascularized composite bladder allograft