Deceased Donor Bladder or Combined Kidney-bladder Transplantation: a Phase 0 First-in-human Study
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-70
SponsorUniversity of California, Los Angeles
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18-70 years
Terminal bladder pathology resulting in poor compliance, recurrent refractory infections, and/or and resultant upper tract (kidney and ureteral) pathology, with possible resultant kidney disease.
Localized, non-metastatic, bladder cancer requiring radical cystectomy. In this protocol, the only patients with a history of urothelial cell carcinoma that has already been treated, with an appropriate disease-free interval would be considered. Moreover, only candidates requiring a joint kidney and bladder transplantation or patients with a pre-existing transplant, on standard immunosuppression, will be considered.
Patients that are on immunosuppression for pre-existing solid organ transplantation will be included in this study.
Disqualifiers
HIV (active or seropositive), active hepatitis B or C, viral encephalitis, untreated sepsis, active tuberculosis, viral encephalitis, toxoplasmosis, varicella zoster virus
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, thrombocythemia, thalassemia, sickle cell disease.
Mixed connective tissue diseases and collagen disorders (can result in poor wound healing after surgery), including: mixed connective tissue disorder; severe deforming rheumatoid arthritis; infectious, post-infectious, or inflammatory (axonal or demyelinating) neuropathy; Ehlers-Danlos syndrome;
lipopolysaccharidosis or amyloidosis (effects nerve regeneration)
Trial design
Design model
Single group
Treatments tested in this trial
Bladder Transplantation
Procedure/SurgeryA 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.
Combined Kidney and Bladder Transplantation
Procedure/SurgeryFor 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.
Treatment groups
5 Participants
are divided into 2 treatment groupsGroup A: Bladder TransplantationExperimental treatment 1 intervention
Group B: Combined Kidney and Bladder TransplantationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Demonstrating the technical success of 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.
Time frame
2 yearsSecondary outcomes
1
Incidence of adverse events after bladder or combined kidney-bladder transplantation
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.
Time frame
2 years2
Incidence of immune rejection after bladder or combined kidney-bladder transplantation
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.
Time frame
2 years3
Evaluate the functionality of the transplanted bladder
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.
Time frame
2 yearsSponsors and contacts
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Source ClinicalTrials.gov