Transplanting both a kidney and a bladder at the same time

Concomitant Renal and Urinary Bladder Allograft Transplantation

This study is testing if it's possible to safely transplant both a kidney and a bladder at the same time in patients who have kidney problems caused by bladder issues.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 1 Year to 60 Years
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Locations: 2 sites (Rochester, Minnesota and 1 other locations)
• Trial ID: NCT04626167 on ClinicalTrials.gov

What this trial studies

This study aims to determine the feasibility of performing concomitant renal and vascularized urinary bladder allograft transplantation in patients with chronic kidney disease due to bladder dysfunction or absence. It is a single-center, prospective, single-group unblinded phase I study that will enroll patients who require surgical intervention for their conditions. Eligible participants will undergo evaluations to confirm their suitability for the dual transplant procedure, which is intended to address both kidney and bladder issues simultaneously.

Who should consider this trial

Good fit: Ideal candidates are males and females aged 1 to 60 with chronic kidney disease secondary to bladder dysfunction or absence, exhibiting 'hostile bladders'.

Not a fit: Patients with conditions unrelated to bladder dysfunction or those who do not meet the specific inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve the quality of life for patients suffering from chronic kidney disease and bladder dysfunction.

How similar studies have performed: While the approach of concomitant transplantation is innovative, similar studies have shown promise in addressing complex organ dysfunctions, though this specific combination is less commonly tested.

Eligibility criteria

Inclusion Criteria:

* Male or female patients between 1 yr. and 60 years of age.
* Subject is willing and able to give signed informed consent, or have a legally authorized representative who is willing and able to give consent. Informed assent will be required for children 6-17 years of age as appropriate or warranted.
* Patients with CKD secondary to neurogenic bladder, lower urinary tract obstruction or other disorders of the urinary bladder.
* Medical need for a bladder transplant, as defined by the presence of exhibiting "hostile bladders" defined as end filling pressure or detrusor leak point pressure (DLPP) of or greater than 40 cm H20 or at below estimated bladder capacity for age, or detrusor overactivity with detrusor sphincter dyssynergia, or new onset of upper urinary tract changes (hydronephrosis, vesicoureteral reflux) in the last 12 months
* If a concomitant kidney transplant is being considered, additionally, estimated GFR less than or equal to 20 mL/min or dialysis. If GFR 20-25 mL/min would also qualify if expected progression is rapid (\>10 mL/min/year)
* Vetting and approval by the Mayo Clinic multidisciplinary transplant team (MDC) for renal transplantation.
* Ability of subject and/or care provider to be successfully trained in clean intermittent catheterization and bladder cycling. Or current use of CIC.
* Utilization of maximally-tolerated dose and regimen of medical therapy (e.g. anticholinergics) or failure to tolerate/contraindications to such agents.
* Psychosocial clearance: Demonstrated commitment to psychological evaluation perioperatively, in which the psychologist must confirm that the subject has the maturity and stable psychosocial environment necessary for this research study.
* Agree to avoid pregnancy for 1 year after surgery through abstinence or approved contraception as noted in Appendix A (female subjects only)
* If patient has a history of malignancy (with the exception of localized non-melanoma skin cancer) the patient must be at least 5 years from termination of treatment without evidence of recurrent disease.

Exclusion Criteria:

* They are pregnant or breastfeeding, or planning a pregnancy during the course of the study, or who are of child bearing potential and not willing to continue using an effective method of birth control (i.e. with a low failure rate of less than 1 percent per year including injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or a vasectomized partner), or
* Any contraindication to general anesthesia or evaluation reveals that the subject cannot safely undergo general anesthesia and post-operative recovery due to severe cardiovascular, pulmonary, neurological, metabolic, or rheumatologic disease (requires special consultation)
* Any contraindication or known anaphylactic or severe systemic reaction to either human blood products or materials of bovine origin
* Subjects with a current positive (\>=5 mm induration for high-risk subjects; otherwise \>=10 mm of induration) purified protein derivative (PPD) test are excluded unless they have completed a full course of treatment for latent TB and have a negative chest x-ray film at enrollment.
* Known history of hypersensitivity to aminoglycosides or fluoroquinolones
* Use of any investigational product within 3 months
* Prior participation in the study
* Currently smoking
* Current incarceration for any reason
* Unwillingness, inability, or unlikely compliance of individual and/or primary caregiver with study related schedules procedures, management, or follow -up in the opinion of the PI and/or co-investigators
* Any circumstance in which the investigator deems participation in the study is not in the subject's best interest
* Subjects with an ALT or AST value \>3 times the upper limit of normal
* Subjects with acute or chronic abdominal skin infections and/or acute or chronic abdominal inflammatory conditions such as inflammatory bowel disease
* Subjects with uncontrolled diabetes defined as HgA1c\>10, unstable cardiac and/or pulmonary disorders, or bleeding disorders
* Active malignant neoplasm (with the exception of localized non-melanoma skin cancer) that is untreated, unresponsive to available treatment, or too recently treated to determine relapse risk.
* Surgical procedure for transplantation cannot be successfully performed for anatomical reasons
* Life expectancy with successful transplantation is estimated to be \<5 years for any reason.
* There is any other disease, physical examination finding, or clinical laboratory result that provides a reasonable suspicion of a disease or condition that contraindicates the procedure or the interpretation of results or render the subject at high risk for treatment complications, or
* Serious or uncontrolled psychiatric illness or disorder that could compromise their understanding of, or compliance with, follow-up visits/care after transplant, or
* Taking medications on specified hourly intervals that may be affected by changes to renal clearance, or
* Hypertension stage II \> 99th percentile, unless they had a complete workup to exclude secondary etiologies other than being overweight, or
* Presence of severe coagulopathy, (hyper or hypo)
* Patient is not up to date on current CDC recommended vaccines

Where this trial is running

Rochester, Minnesota and 1 other locations

• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Patricio Gargollo, MD — Mayo Clinic
• Study coordinator: Vidhu Joshi

Conditions Chronic Kidney Diseases; Bladder Dysfunction; Bladder Absence; Posterior Urethral Valve; Neurogenic Bladder; Bladder Exstrophy; Bladder Outlet Obstruction; Failure, Kidney