Vascularized Composite Bladder Allograft Transplantation

Launched by UNIVERSITY OF SOUTHERN CALIFORNIA · Jul 15, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at a new type of surgery called vascularized composite bladder allograft transplantation. This procedure aims to help people with severe bladder problems, especially those whose bladders are not functioning properly due to conditions like neurogenic bladder or bladder cancer. Instead of using a piece of bowel for urinary diversion, which is the standard method, this study explores whether a transplanted bladder can work better and be more comfortable for patients. The surgery will be performed using robotic technology, which helps ensure precision and reduce recovery time.

To be eligible for this trial, participants need to be between 18 and 65 years old and have a history of significant bladder issues leading to recurrent infections or kidney problems. Those already on medications that suppress the immune system might also be considered. Participants will need to demonstrate the ability to manage their catheter care, which involves a simple procedure to help them urinate after the transplant. Throughout the study, participants can expect close monitoring and support to ensure their health and safety. It's important to note that the trial has strict guidelines to ensure that only suitable candidates are included, focusing on those who can commit to the necessary follow-up and treatment plans.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age 18-65 years.
• * Positive history of one of the following:
• • Bladder pathology resulting in poor compliance, recurrent infections, and/or resultant upper tract (kidney and ureteral) pathology, demonstrated by hydronephrosis with resultant kidney disease.
• • Localized, non-metastatic, muscle-invasive or lesser urothelial cell carcinoma of the bladder that requires therapeutic radical cystectomy will be considered only if the patient is already on pre-existing immunosuppression or who are expected candidates for immunosuppression in the near future, and then on a case-by-case basis after thorough evaluation and presentation to institutional tumor board committee. A minority of accrued patients are expected to have bladder cancer as the etiology of their cystectomy.
• • Patients that are on pre-existing immunosuppression will be included in this study.
• • Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.
• • Patients must demonstrate appropriate manual dexterity or sufficient assistance at home to perform clean intermittent catheterizations as needed. The patient (or assistant) must demonstrate proficiency in performing clean intermittent catheterization during pre-transplant workup.
• • No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (see Exclusion Criteria below). If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of genitourinary transplantation. Examples of such medical conditions would include a burden of atherosclerotic disease that would preclude vascular anastomosis, and psychiatric disorders that would preclude reliable adherence to medications.
• • No active co-existing psychosocial problems (i.e., alcoholism, drug abuse).
• • Negative crossmatch with donor.
• • DONOR: Any potential brain dead donor considered for solid organ transplant.
• • DONOR: Age 18-65 years.
• • DONOR: Stable, meaning no requirement of excessive vasopressors for maintaining blood pressure.
• • DONOR: ABO compatibility.
• • DONOR: Negative cross-match with recipient.
• Exclusion Criteria:
• * Positive history of one of the following medical co-morbidities:
• • Human immunodeficiency virus \[HIV\] (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, thallassemia, 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
• • Ehler-Danlos syndrome
• • Lipopolysaccharidosis or amyloidosis (effects nerve regeneration).
• • Impaired liver function as evaluate by liver function panel, including the presence of hyperbilirubinemia, elevated aspartate aminotransferase/ alanine aminotransferase (AST/ALT), and the presence of secondary coagulopathy, measured by prothrombin, international normalized ratio, and partial thromboplastin time.
• • Severe anemia (hemoglobin \< 7 g/dL), leukopenia (WBC \< 3 x 10 \^ 9 cell/L), or thrombocytopenia (platelets \< 20 x10 \^ 9 cells/L).
• * Oncology patient specific:
• • History of any non-urothelial malignancy within the past 5 years, with the exception of non-melanomatous skin cancer and very-low to low risk prostate cancer on active surveillance.
• • History of metastasic malignancy within the past 5 years.
• • History of urothelial carcinoma in patients without pre-existing conditions that require immunosuppression and/or without the expected need for immunosuppression in the future.
• • Sensitized recipients; panel reactive antibody (PRA) \< 80%, with negative crossmatch to donor and no evidence of donor-specific antibody at time of transplant.
• • Patients unable to receive adequate follow-up care and/or unable to receive immunosuppression due to geographic, financial or other reasons.
• • Patients with a smoking history who cannot demonstrate smoking cessation for a period of 6 months prior to listing and a desire to abstain from post-operative smoking will be excluded.
• • Records of poor medical compliance, documented psychological disorder(s), substance abuse or incomplete psychological clearance.
• • Particular attention will be paid to the candidate's compliance and their desire to undergo the offered procedure. While there is no "score" on any particular evaluation that would rule out a patient, certain factors can aid in the identification of patients who for example may not have the ability to comply with the medical directives necessary to care for a genitourinary transplant, or psychologically are not prepared for transplant, or who have unrealistic expectations about the transplant. The decision on eligibility is a team decision. All members of the team will discuss each candidate in a multidisciplinary meeting and reasons for concern over eligibility will be discussed at a Selection Committee Meeting (per University of Southern California Transplant Center Policy). In circumstances where the candidate is considered to be less suitable, they could be given an opportunity to address these issues either through individual counseling or further education and then be reconsidered as a potential candidate. Every effort to prevent a request for allograft removal will be made. Towards these ends, a two-part initial psychiatric consultation will be rendered in addition to psychosocial evaluations already accounted for in the social work and transplantation evaluation prior to listing. The first visit focuses on background history and standard contraindications to transplantation, while the second visit is a more thorough discussion of the challenges ahead for the potential recipient and how these challenges relate to their strengths and vulnerabilities. If at this phase, or any subsequent one, significant psychological need emerges, the patient will be referred to another mental health professional for ongoing treatment with frequent communication between that provider and the transplant psychiatrist. The same psychiatrist responsible for listing and taking part in the protocol will not provide this treatment, given the potentially conflicting obligations involved and the disincentive present for the patient to be completely honest. If a greater than 6 month period of time elapses between listing and transplantation, a follow-up visit with psychiatry and social work will be arranged.
• • DONOR: Unresolved sepsis.
• • DONOR: Known history of urothelial or prostate cancer/malignancy.
• • DONOR: Known history of bladder or prostate surgery.
• • DONOR: Abnormal bladder capacity.
• • DONOR: Active sexually transmitted disease.
• • DONOR: Active cytomegalovirus (CMV), Epstein-Barr virus (EBV), or tuberculosis (TB) infections.
• • DONOR: Hepatitis B virus (HBV) core antibody, surface antigen, or DANN positive.
• • DONOR: Hepatitis C virus (HCV) antibody or viral load+.
• • DONOR: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).