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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2024
• Main ID: NCT06337942
• Date of registration: 15/03/2024
• Prospective Registration: Yes
• Primary sponsor: University of California, Los Angeles
• Public title: Deceased Donor Bladder or Combined Kidney-bladder Transplantation: a Phase 0 First-in-human Study
• Scientific title: Vascularized Composite Bladder Allograft Transplantation: a Phase 0 (First-in-human) Study for Deceased Donor Bladder or Combined Kidney-bladder Transplantation
• Date of first enrolment: April 1, 2024
• Target sample size: 5
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT06337942
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: Dana Lopez, MPH

• Name: Magdalena Mendez-Smith

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age 18-70 years

- Positive history of one of the following:

1. 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.

2. 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.

- Patient agrees to comply with the protocol and states a dedication to the
immunomodulatory treatment regime.

- Patient has been previously fully vaccinated and boosted against COVID-19, or is
willing to undergo timely vaccination.

(a) Caretakers of the recipient will be strongly encouraged to be vaccinated.

- 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. 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 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.

Exclusion Criteria:

- Positive history of one of the following medical co-morbidities:

1. HIV (active or seropositive), active hepatitis B or C, viral encephalitis,
untreated sepsis, active tuberculosis, viral encephalitis, toxoplasmosis,
varicella zoster virus

2. 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.

3. 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;

4. lipopolysaccharidosis or amyloidosis (effects nerve regeneration)

5. Impaired liver function as evaluated by liver function panel, including the
presence of hyperbilirubinemia, elevated AST/ALT, and the presence of secondary
coagulopathy, measured by prothrombin, international normalized ratio, and
partial thromboplastin time.

6. Severe anemia (hemoglobin < 7 g/dL), leukopenia (WBC < 3 x 109 cell/L), or
thrombocytopenia (platelets < 20 x109 cells/L).

- Patient is either not vaccinated or is unwilling to undergo vaccination against
COVID-19 prior to transplantation.

- Oncology patient specific:

1. History of non-urothelial malignancy in past 5 years, with the exception of
non-melanomatous skin cancer

2. History of malignancy involving metastases

- 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. 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Bladder, Neurogenic

Bladder Disease

Bladder Cancer

Kidney Failure

Intervention(s)

Procedure: Combined Kidney and Bladder Transplantation

Procedure: Bladder Transplantation

Primary Outcome(s)

Demonstrating the technical success of bladder or combined kidney-bladder transplantation [Time Frame: 2 years]

Secondary Outcome(s)

Incidence of immune rejection after bladder or combined kidney-bladder transplantation [Time Frame: 2 years]

Evaluate the functionality of the transplanted bladder [Time Frame: 2 years]

Incidence of adverse events after bladder or combined kidney-bladder transplantation [Time Frame: 2 years]

Secondary ID(s)

23-001621

Source(s) of Monetary Support

Please refer to primary and secondary sponsors