Clinical trial NCT05054790: Augmentation Cystoplasty Using an Autologous Neo-Bladder Construct
Official title: A Phase 2 Study of Augmentation Cystoplasty Using an Autologous Neo-Bladder Construct In Subjects With Fibrotic Contracted Bladder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Contracted Bladder
Keywords: Neo-bladder
fibrotic bladder
bladder compliance
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2021-09-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to find out if autologous "neo-bladder" construct for the treatment of fibrotic and/or contracted bladder can improve bladder compliance and be safe long term. The neo-bladder is like a reservoir or pouch that will be surgically attached to the bladder to assist with urine collection.

Detailed description: This is a prospective, open-label, single-group clinical study. All subjects will have non-neurogenic, fibrotic contracted bladder that is refractory to medical treatment and require augmentation cystoplasty for preventing long-term sequelae (i.e., kidney failure) that result from persistently high intravesical pressure. Subjects will undergo an open full thickness bladder biopsy from which autologous urinary bladder smooth muscle and urothelial cells will be procured and expanded ex vivo. After approximately 5 - 7 weeks, expanded cells will be seeded on a biodegradable scaffold to produce the neo-bladder construct that will be surgically implanted onto an opened native bladder during an augmentation cystoplasty. Subjects will be followed for 36 months.

Eligibility criteria: Inclusion Criteria:

* Subjects with small contracted and/or fibrotic non-neurogenic bladder.
* Small bladder \<150cc capacity
* Willing and able to give signed informed consent in English.
* Ability of subject to be successfully trained in clean intermittent catheterization and bladder cycling
* Failure to respond to maximum approve dose of medical therapy (e.g. anticholinergics) or failure to tolerate /contraindication to such agents
* Medical need for bladder augmentation, as defined by the presence of:

  1. Decreased and inadequate bladder compliance with a bladder pressure ≥40 cmH20. OR
  2. New-onset of upper urinary tract changes (hydronephrosis, vesicoureteral reflux) in the last 12 months

Exclusion:

* Neurogenic bladder
* Recent (\< 12 months) urological or intraperitoneal surgery or device implantation; recent (\<6 month neurologic surgery-brain or spine)
* Any prior bladder augmentation procedure
* Known or suspected limitation to obtaining omentum for implantation procedure (e.g., extensive intraperitoneal adhesions)
* Any contraindication to general anesthesia
* Any contraindication or known anaphylactic or severe systemic reaction to either human blood products or materials of bovine origin
* Human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV), active hepatitis A (HAV) or other known active infection
* Subjects with active tuberculosis (TB) requiring treatment in the past 3 years. 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.
* Subjects known to be colonized with either methicillin-resistant staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE), or gentamicin-resistant organisms.
* Receipt of blood or blood products for transfusion during the 3 months prior to biopsy
* Immunocompromised subjects or subjects receiving immunosuppressive agents (inhaled corticosteroids and chronic low-dose corticosteroids \[≤0.25 mg/kg prednisone or equivalent per day\] are permitted).
* Brief pulsed corticosteroids for intermittent symptoms (e.g., asthma) are permitted.
* Known history of hypersensitivity to aminoglycosides or fluoroquinolones.
* History of true allergy to iodine or iodinated x-ray contrast agents
* Use of any investigational product within 3 months
* Prior participation in the study
* Any history of alcohol and/or any drug abuse
* Current incarceration for any reason
* Unwillingness, inability, or unlikely compliance with study related procedures
* Any circumstance in which the investigator deems participation in the study is not in the subject's best interest
* Subjects with an Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) value \>3 times the upper limit of normal
* Subjects with an albumin value \<3.0 g/dL
* Subjects with a history of an anaphylactic or a severe systemic reaction to the biodegradable polymers glycolic acid (PGA) and lactic-co-glycolic acid (PLGA)
* Subjects with acute or chronic abdominal skin infections and/or acute or chronic inflammatory bowel disease
* Subjects with uncontrolled diabetes, unstable cardiac and/or pulmonary disorders, or bleeding disorders
* Subjects who have received Botulinum Toxin A injections into the bladder within the previous 12 months.
* Female subjects who are pregnant, planning to get pregnant or lactating/breast-feeding.
* Female subjects of child-bearing potential unwilling to practice an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy) for duration of the study.

  * If a patient has had a hysterectomy, a bilateral oophorectomy, documented ovarian failure or is older than age 51.5 years and has not had a menstrual period in more than 12 months, they will be considered to be non-childbearing. This will be ascertained from patient interview/self-report, medical records (if necessary) and the investigator's judgment. "Spontaneous menopause," occurs in the United States at a mean age of 51.5 years.

Primary outcomes:
measure: Bladder Compliance Average
timeFrame: Month 12
measure: Average Number of 24 Hour Voids
timeFrame: Month 6
measure: Average Number of 24 Hour Voids
timeFrame: Month 9
measure: Average Number of 24 Hour Voids
timeFrame: Month 12
Secondary outcomes:
measure: Change in Bladder Capacity
timeFrame: From Baseline through Month 12
measure: End filling pressure
timeFrame: Baseline, Month 6, Month 9 and Month 12
measure: Urogenital Distress Inventory-6 Question (UDI-6)
timeFrame: Month 6, Month 9 and Month 12
measure: Urogenital Distress Inventory-7 Question (UDI-7)
timeFrame: Month 6, Month 9 and Month 12
measure: Genitourinary Pain Index (GUPI)
timeFrame: Month 6, Month 9 and Month 12
measure: Quality of Life (QOL) Questionnaire
timeFrame: Month 6, Month 9 and Month 12
measure: American Urological Association Symptom Score (AUASS)
timeFrame: Month 6, Month 9 and Month 12
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
Study officials:
affiliation: Atrium Health Wake Forest Baptist
name: Robert J. Evans, MD
role: PRINCIPAL_INVESTIGATOR
References: