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Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures

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ClinicalTrials.gov Identifier: NCT03258658
Recruitment Status : Suspended (Pending FDA review)
First Posted : August 23, 2017
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.


Condition or disease Intervention/treatment Phase
Urologic Diseases Male Urogenital Diseases Urethral Stricture Urethral Injury Biological: Autologous Engineered Urethral Construct Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Pilot Safety and Feasibility Study of Autologous Engineered Urethral
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2024

Arm Intervention/treatment
Experimental: 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.
Biological: Autologous Engineered Urethral Construct
urethral construct




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Effectiveness of urethral construct in repairing urethral stricture [ Time Frame: monitored through 36 months post construct implant ]
    Improvement in peak urinary flow rate defined as Qmax improvement from baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Stricture of the anterior urethra meeting the following criteria:

    1. History of at least one previously failed attempt at conservative management, at least 6 months prior to study.
    2. Urethral stricture of 10-60 mm in length, as determined by urethrography.
    3. Contains at least 1 strictured segment through which a 16 Fr flexible cystoscope cannot be atraumatically passed.
  2. Patients must be available for all follow-up visits.
  3. Ability to speak English.

Exclusion Criteria:

Any of the following is regarded as a criterion for excluding a subject from the study:

  1. 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.
  2. Presence of untreated urinary tract infection.
  3. Presence or prior history of lichen sclerosus et atrophicus (previously termed 'balanitis xerotica obliterans').
  4. Uncontrolled bleeding disorder or patients with a platelet count less than 50,000, hemophilia or patients routinely receiving blood products for bleeding disorders.
  5. 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).
  6. Serum creatinine > 2.0 mg/dl or evidence of progressive renal disease.
  7. Patients with abnormal urologic conditions, including vesicoureteral reflux, bladder stones, bladder tumors and renal impairment.
  8. Subjects with an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >3 times the upper limit of normal.
  9. Subjects with an albumin value <3.0 g/dL.
  10. Subjects with uncontrolled diabetes, unstable cardiac and/or pulmonary disorders.
  11. 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.
  12. Subjects known to be colonized with either methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE), or gentamicin-resistant organisms.
  13. 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).
  14. Any history of alcohol and/or drug abuse.
  15. Current smoker.
  16. 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.
  17. 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.
  18. 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.
  19. Any circumstance in which the investigator deems participation in the study is not in the subject's best interest.
  20. Inability to participate in all necessary study activities due to physical or mental limitations.
  21. Inability or unwillingness to return for all required follow-up visits.
  22. Inability or unwillingness to sign informed consent.
  23. Patients requiring concomitant use of or treatment with immunosuppressive agents.
  24. Patients with neurological disorders (e.g., multiple sclerosis, Parkinson's disease).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03258658


Locations
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United States, North Carolina
Wake Forest Institute for Regenerative Medicine (WFIRM)
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
United States Department of Defense
Investigators
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Principal Investigator: Ryan P Terlecki, MD Associate Professor

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03258658     History of Changes
Other Study ID Numbers: IRB00043624
W81XWH-13-2-0052 ( Other Grant/Funding Number: Department of Defense )
First Posted: August 23, 2017    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences:
Urethral Stricture

Additional relevant MeSH terms:
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Constriction, Pathologic
Urologic Diseases
Urethral Stricture
Pathological Conditions, Anatomical
Urethral Obstruction
Urethral Diseases