Tissue-engineered Construct Based on Buccal Mucosa Cells and Matrix From Collagen and Polylactoglycolide Fibers

An Open Prospective Clinical Study on Safety and Efficacy of Surgical Treatment of Patients With Anterior Urethral Stricture Using a Tissue-engineered Construct Based on Autologous Buccal Mucosa Cells and Matrix From Reconstituted Collagen and Reinforcing Polylactoglycolide Fibers

This study investigates safety and efficacy of surgical treatment of patients with anterior urethral stricture using a tissue-engineered construct based on autologous buccal mucosa cells and matrix from reconstituted collagen and reinforcing polylactoglycolide fibers. This is a single arm study with no control. Success will be assessed via objective and subjective methods; complications will be tallied in a standardized fashion. Outcomes will be measured at five years.

Study Overview

• Status: Unknown
• Conditions: Urethral Stricture
• Intervention / Treatment: Procedure: Urethroplasty with a tissue-engineered construct

Detailed Description

Treatment of urethral strictures longer than 2 cm is an actual clinical challenge. In this case, the common method is replacement surgery using a buccal mucosa graft. However, the main disadvantage of this method is associated with limited donor resources and donor site morbidity.

The aim of this study is to assess safety and efficacy of surgical treatment of patients with anterior urethral stricture using a tissue-engineered construct. The construct consists of autologous buccal mucosa cells and matrix from reconstituted collagen and reinforcing polylactoglycolide fibers. Patients will be followed up for 5 years within this study. The follow-up regimen includes retrograde and pericatheter urethrography, voiding cystourethrography, uroflowmetry, biopsy, and quality of life monitoring. Telephone follow-up will take place in between these assessments.

The data obtained from this study will have practical implications for the urethral stricture treatment and will be based on the principles of evidence-based medicine.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Sechenov University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patient signed informed consent form
• Diagnosed anterior urethral stricture longer than 2.0 cm and shorter than 4.0 cm
• At least one prior internal optical urethrotomy and/or urethral bougienage

Non-inclusion Criteria:

• Acute infectious diseases
• Patient with decompensated heart and renal failure
• Patient with non-compensated diabetes mellitus
• Patient with malignant tumor
• Patient with polyvalent allergy
• Mental disorders
• Post traumatic urethral strictures
• Subtotal and total urethral strictures
• Sexually transmitted infections
• Hypersensitivity to any components of tissue-engineered constructs
• Any clinical state which does not ensure the safe implementation of study procedure (investigator's view)
• Other associated urethral strictures
• Laboratory markers of active urethritis

Exclusion Criteria:

• Patient's refusal from the further participation in trial
• Confirmed syphilis, HIV, hepatitis B or C infections
• Patient who cannot be regularly examined due to any circumstances

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Urethroplasty with a tissue-engineered construct; The investigators will take a sample of the buccal mucosa to isolate epithelial cells. Autologous cells will be seeded on a hybrid matrix. Urethroplasty with this tissue-engineered construct will be performed. This is a single arm study with no control. All patients will undergo the surgical operation.	Procedure: Urethroplasty with a tissue-engineered construct; The investigators will perform urethroplasty with the tissue-engineered construct - epithelial cells isolated from patient's buccal mucosa and seeded on a collagen-polylactoglycolide matrix.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events	Frequency, type and severity of serious adverse events (SAE)	4 weeks after surgery
Serious adverse reactions	Frequency, type and severity of serious adverse reactions (SAR)	4 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retrograde urethrography	Influence of the surgery on the urethral lumen	5 years
Voiding cystourethrography	Full assessment of the urethral lumen after the surgery	5 years
Pericatheter urethrography	Assessment of absence or presence of contrast medium leakage outside the urethra	4 weeks after surgery
Biopsy	Control of anatomical urethral structure in the intervention place	4 months after surgery
Urodynamic changes via uroflowmetry - 1	Influence of the surgery on urinary flow rate: maximum flow rate	5 years
Urodynamic changes via uroflowmetry - 2	Influence of the surgery on urinary flow rate: average flow rate	5 years
Urodynamic changes via uroflowmetry - 3	Influence of the surgery on urinary flow rate: total volume voided	5 years
Urodynamic changes via uroflowmetry - 4	Influence of the surgery on urinary flow rate: maximum flow time	5 years
Quality of life monitoring - 1	Quality of life estimated by validated questionnaires: Short Form (SF-36)	5 years
Quality of life monitoring - 2	Quality of life estimated by validated questionnaires: International Prostatic Symptom Score (IPSS)	5 years

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Denis Butnaru, Dr., Sechenov First Moscow State Medical University; Principal Investigator: Andrey Vinarov, Dr., Prof., Sechenov First Moscow State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: June 26, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 14, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Collagen; Autologous Cells; Buccal Mucosa; Urethroplasty; Tissue-engineered Construct; Hybrid matrix; Polylactoglycolide Fibers
• Additional Relevant MeSH Terms: Urologic Diseases; Pathological Conditions, Anatomical; Urethral Diseases; Urethral Obstruction; Constriction, Pathologic; Urethral Stricture
• Other Study ID Numbers: SU-IRM-2017-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No