Bladder or Combined Kidney-Bladder Transplants for Bladder Disease

Overseen By Gina Choi

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must be taking: Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

5 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on immunosuppression for a pre-existing organ transplant, you will continue with that treatment.

What data supports the effectiveness of this treatment for bladder disease?

Research shows that kidney transplants into reconstructed bladders have similar survival rates to those into normal bladders, despite higher complications. This suggests that combining kidney and bladder transplants might be feasible, although more studies are needed to confirm effectiveness. ^{1 2 3 4 5}

Is bladder or combined kidney-bladder transplantation safe in humans?

There is limited safety data specifically for bladder or combined kidney-bladder transplants in humans, but studies on kidney transplants in patients with bladder issues suggest that while there may be more complications, survival rates are similar to those without bladder issues. ^{1 3 4 5 6}

How is the treatment of bladder or combined kidney-bladder transplants unique for bladder disease?

This treatment is unique because it involves transplanting a whole bladder or a combined kidney and bladder from a deceased donor, which has never been done in humans before. It aims to address complex bladder diseases by replacing the entire organ, unlike other treatments that may only reconstruct or augment the existing bladder. ^{1 2 5 6 7}

What is the purpose of 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 is for individuals with severe bladder conditions or kidney failure who might benefit from a new bladder or both a new bladder and kidney. Participants should be in need of these transplants due to terminal diseases affecting these organs.

Inclusion Criteria

My caretakers are strongly advised to get vaccinated.

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

Patients must demonstrate appropriate manual dexterity or sufficient assistance at home to perform clean intermittent catheterizations

Exclusion Criteria

I have a connective tissue or collagen disorder.

I do not have active HIV, hepatitis B or C, viral encephalitis, untreated sepsis, active tuberculosis, toxoplasmosis, or varicella zoster virus.

Severe anemia, leukopenia, or thrombocytopenia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo bladder-only or combined kidney and bladder transplantation

Immediate

1 visit (in-person)

Initial Follow-up

Participants are monitored for immediate peri-operative, 30, and 90-day adverse profiles

3 months

Regular visits (in-person)

Long-term Follow-up

Participants are monitored for efficacy, safety, and functionality of the bladder transplant

2 years

Regular visits every 3 months (in-person)

Treatment Details

Interventions

• Bladder Transplantation
• Combined Kidney and Bladder Transplantation

Trial Overview The study is testing the feasibility and safety of transplanting a human bladder alone, or together with a kidney, into patients. It will assess how well the transplanted bladder can store urine and facilitate its release over two years.

Participant Groups

Group I: Combined Kidney and Bladder Transplantation Experimental Treatment 1 Intervention

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

Group II: Bladder Transplantation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

Renal transplantation in patients with reconstructed bladders has higher urologic complications, but overall graft and patient survival rates are similar to those with non-reconstructed bladders, based on a review of 25 articles.

It is recommended that bladder reconstruction be done prior to kidney transplantation when necessary, as this may help manage complications more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal transplantation in children with reconstructed bladders. Franc-Guimond, J., González, R.[2022]

The study demonstrated that urinary bladder vascularized composite allograft transplantation is technically feasible, as shown by successful mock transplants in two adult cadavers, indicating potential for future clinical applications.

This innovative approach could provide an alternative to using intestinal segments for bladder reconstruction, which may improve patient outcomes and reduce complications associated with intestinal grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver Model. Gargollo, PC., Ahmed, ME., Prieto, M., et al.[2021]

Kidney transplant recipients with prior bladder surgery face a significantly higher risk of graft failure and increased urinary complications, with a hazard ratio of 3.57 for graft survival, indicating a need for careful recipient selection.

Post-operative complications were notably higher in recipients with bladder dysfunction (35%) and those with bladder substitutes (52.3%), compared to only 12.8% in those with normal bladder function, highlighting the importance of monitoring these patients closely after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Kidney Transplant Recipients with Bladder Dysfunction: A Single-Center Study. Srinivasan, D., Stoffel, JT., Mathur, AK., et al.[2019]

In a study of 58 pediatric patients, three with severe bladder dysfunction who underwent augmentation cystoplasty prior to renal transplantation showed normal kidney function and no complications at follow-up periods of 13 to 49 months.

Augmentation cystoplasty appears to be a safe and effective treatment for these patients, with all subjects remaining continent and experiencing manageable urinary tract infections without affecting kidney graft function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal transplantation in children with augmentation enterocystoplasty. Aki, FT., Besbas, N., Ozcan, O., et al.[2006]

The study demonstrated that vascularized total bladder transplantation alongside kidney transplantation is feasible, as all grafts showed good blood supply and normal oxygen saturation during the observation period.

While one recipient experienced thrombosis leading to reduced urinary output, the other two recipients maintained normal bladder function, suggesting that with careful monitoring, this procedure could serve as a viable option for bladder augmentation or replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined kidney and vascularized total bladder transplantation: experience in an animal model. Torino, G., Capozza, N., Diomedi Camassei, F., et al.[2015]

In a study comparing 9 kidney transplant recipients who underwent simultaneous bladder augmentation (BA-KT) with 22 who had kidney transplants only, the BA-KT group showed better early graft function, with a higher estimated glomerular filtration rate (96.5 mL/min vs. 79.4 mL/min) within the first 6 months.

However, the BA-KT group experienced significantly higher rates of urinary tract infections (100% vs. 23% in the KT only group) and complications related to posttransplant care, leading to a notable decline in graft function by the fifth year, with only 66% of grafts functioning compared to 100% in the KT only group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation Procedure in Pediatric Patients. Cleper, R., Ben Meir, D., Krause, I., et al.[2022]

This study successfully developed a technique for robotic retrieval and autotransplantation of vascularized bladder allografts in preclinical models, including living pigs and human cadavers, paving the way for future human trials.

The procedure demonstrated technical success with healthy revascularized autografts and maintained vascularity in heart-beating brain-dead donors, indicating the potential for safe and effective bladder transplantation in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant. Nassiri, N., Cacciamani, G., Gill, IS.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Renal transplantation in children with reconstructed bladders. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver Model. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Kidney Transplant Recipients with Bladder Dysfunction: A Single-Center Study. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Renal transplantation in children with augmentation enterocystoplasty. [2006]

5. United States pubmed.ncbi.nlm.nih.gov

Combined kidney and vascularized total bladder transplantation: experience in an animal model. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation Procedure in Pediatric Patients. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant. [2023]