Using engineered urethral constructs to treat urethral strictures in men

A Phase 1 Pilot Safety and Feasibility Study of Autologous Engineered Urethral

This study is testing a new way to treat urethral strictures in men by using specially grown tissue from their own bladder to see if it helps them feel better over time.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 21 Years to 75 Years
• Sex: Male
• Sponsor: Wake Forest University Health Sciences (Academic / other)
• Drugs / interventions: prednisone
• Locations: 2 sites (San Francisco, California and 1 other locations)
• Trial ID: NCT03258658 on ClinicalTrials.gov

What this trial studies

This Phase I clinical study aims to evaluate the safety and efficacy of autologous engineered urethral constructs for treating urethral strictures in adult males. The study involves a prospective, non-randomized, and uncontrolled design at a single center. Male participants aged 21-65 with recurrent urethral strictures will have bladder tissue biopsies to obtain urothelial and smooth muscle cells, which will be cultured and used to create urethral constructs. After approximately six weeks, subjects will undergo surgical implantation of these constructs and will be followed for 36 months to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 21-65 with recurrent urethral strictures that have not responded to previous treatments.

Not a fit: Patients with strictures associated with urethral carcinoma or those with very short or very long strictures may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel and effective treatment option for men suffering from urethral strictures.

How similar studies have performed: While this approach is innovative, similar studies using engineered tissues for urological applications have shown promise, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Stricture of the urethra meeting the following criteria:

  a) History of at least one 15-60 mm in length, as determined by urethrography. c) 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 sclerosis 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.
* 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.
* 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).
* Any history of alcohol and/or drug abuse.
* Current smoker.
* Documented history of, or positive result of HIV, Hepatitis B or C, or any infectious disease. External signs, sequelae, or positive serology of sexually transmitted disease (including HPV).
* Patients with a history of systemic conditions, including but not limited to HIV, diabetes and chronic liver disease (including Hepatitis B or C), that the Investigator believes may jeopardize the safety of the patient to participate in the study.
* Concurrent participation in any other clinical investigation during the period of this investigation. Patients who have been treated with any other investigational drug or participated in any investigational study within 30 days prior to enrollment in this study.
* Any current illness that might confound the results of this investigation, including but not limited to bladder atonia, neuropathic/neurogenic bladder, bladder outlet obstruction (other than urethral stricture), sphincteric dysfunction, or spinal cord injury.
* Any circumstance in which the investigator deems participation in the study is not in the subject's best interest.
* Inability to participate in all necessary study activities due to physical or mental limitations.
* Inability or unwillingness to return for all required follow-up visits.
* inability or unwillingness to sign informed consent.
* Patients requiring concomitant use of or treatment with immunosuppressive agents.
* Patients with neurological disorders (e.g., multiple sclerosis, Parkinson's disease).

Where this trial is running

San Francisco, California and 1 other locations

• University of California San Francisco — San Francisco, California, United States (Not_yet_recruiting)
• Wake Forest Institute for Regenerative Medicine (WFIRM) — Winston-Salem, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: James Yoo, MD — Wake Forest Institute for Regenerative Medicine
• Study coordinator: Mary-Clare Day, RN, BSN

Conditions Urologic Diseases; Male Urogenital Diseases; Urethral Stricture; Urethral Injury