A Phase 1 Pilot Safety and Feasibility Study of Autologous Engineered Urethral
Overview
- Phase
- Phase 1
- Intervention
- Autologous Engineered Urethral Construct
- Conditions
- Urologic Diseases
- Sponsor
- Wake Forest University Health Sciences
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Incidence of product-related, biopsy procedure-related, and injection procedure-related adverse events
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This is a Phase I clinical study to determine the safety and efficacy of using autologous, engineered urethral constructs for the treatment of urethral strictures in adult males.
The proposed study design is a prospective non-randomized and uncontrolled single-center investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and used to seed tubular PGA scaffolds to create autologous urethral constructs for the repair of urethral strictures.
Detailed Description
This is a Phase I clinical study to determine the safety and efficacy of using autologous, engineered urethral constructs for the treatment of urethral strictures in adult males. The proposed study design is a prospective non-randomized and uncontrolled single-center investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and used to seed tubular Polyglycolic Acid (PGA) scaffolds to create autologous urethral constructs for the repair of urethral strictures. Male patients, aged 21-65 years old, seen in the Wake Forest Baptist Health urology clinic, referred to or self-referred to the study team, with recurrent urethral stricture, previously treated with dilation, internal urethrotomy, or urethroplasty, will be approached and offered consent to participate in in the trial. Up to 20 men may undergo screening procedures to identify 10 eligible subjects meeting all inclusion and exclusion criteria. All eligible subjects will undergo full thickness bladder tissue biopsies at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina to obtain UCs and SMCs, which will be cultured and expanded and then seeded on tubular PGA scaffolds. Approximately 6 weeks after biopsy, the subjects will return to undergo surgical removal of the stricture and implant of the urethral construct. Subjects will be followed through 36 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Stricture of the anterior urethra meeting the following criteria:
- •History of at least one previously failed attempt at conservative management, at least 6 months prior to study.
- •Urethral stricture of 10-60 mm in length, as determined by urethrography.
- •Contains at least 1 strictured segment through which a 16 Fr flexible cystoscope cannot be atraumatically passed.
- •Patients must be available for all follow-up visits.
- •Ability to speak English.
Exclusion Criteria
- •Strictures of the meatus or prostatic urethra; any urethral stricture associated with or suspected to be urethral carcinoma, or strictures due to pelvic distraction injuries. Strictures \<10 mm or \>60 mm, as determined by urethrography, and criteria for bulbar urethral strictures excluding those with strictures \<20 mm and \>60 mm, as described by urethrography.
- •Presence of untreated urinary tract infection.
- •Presence or prior history of lichen sclerosus et atrophicus (previously termed 'balanitis xerotica obliterans').
- •Uncontrolled bleeding disorder or patients with a platelet count less than 50,000, hemophilia or patients routinely receiving blood products for bleeding disorders.
- •Any urological condition that would be likely to require additional urethral instrumentation during the period of investigation, including, but not limited to benign prostatic hyperplasia requiring treatment, use of alpha blockers, active prostate cancer, an unevaluated elevated prostate surface antigen (PSA), bladder cancer, or any recurrent urinary stone formation. Patients with evidence or diagnosis of any coagulation disorder (including concomitant anti-coagulation therapy at enrollment).
- •Serum creatinine \> 2.0 mg/dl or evidence of progressive renal disease.
- •Patients with abnormal urologic conditions, including vesicoureteral reflux, bladder stones, bladder tumors and renal impairment.
- •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 uncontrolled diabetes, unstable cardiac and/or pulmonary disorders.
Arms & Interventions
Autologous Engineered Urethral Construct
All subjects enrolled will undergo a full-thickness bladder biopsy as an out-patient surgical procedure. Urothelial and Smooth Muscle Cells recovered from the biopsy will be isolated and expanded over the next 4-6 weeks, and then seeded onto a tubular scaffold to create the autologous engineered urethral construct. Subjects will undergo a second surgical procedure to excise the urethral stricture and implant the urethral construct. All subjects will be followed for 3 years for safety and efficacy.
Intervention: Autologous Engineered Urethral Construct
Outcomes
Primary Outcomes
Incidence of product-related, biopsy procedure-related, and injection procedure-related adverse events
Time Frame: monitored through 36 months post treatment
Rate of adverse events reported for each patient
Secondary Outcomes
- Effectiveness of urethral construct in repairing urethral stricture(monitored through 36 months post construct implant)