Transurethral Myoblast Injection for Urinary Incontinence in Children With Bladder Exstrophy

NCT02075216 | Unknown Phase 1 DMC

• 2 other identifiers: NCT1502231Azhar2013298
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Muscle precursor cells constantly regenerate striated muscles, and include the quiescent satellite cells located beneath the basal lamina of skeletal myofibers, which are responsible for repair of the terminally differentiated striated muscle tissue. Transurethral implantation of autologous myoblasts may represent an improved alternative to synthetic bulking agents, with the unique ability to compensate for the deficient muscle fibers in the urethral sphincter. Clinical studies of cell therapy based treatment of sphincter insufficiency, using muscle derived stem cell transplantation was carried out in patients with stress incontinence revealed and confirmed the ability of cell therapy to improve the structure and contractile function of the sphincter. In this study autologous heterotopic myoblasts will be transurethrally injected in patients with bladder extrophy epispadias complex who remained incontinent after staged bladder reconstruction and bladder neck reconstruction. The aim of this study is to investigate the potential therapeutic effects of autologous myoblast injection for the treatment of children presenting with urinary incontinence after modern staged repair and bladder neck reconstruction of extrophy-epispadias complex as well as studying the safety, efficacy and durability of the procedure, and health related quality of life.

Conditions

Urinary Incontinence

Keywords

Urinary Incontinence; Children; Bladder Exstrophy; Extrophy -Epispadias complex,; Modern staged repair,; Bladder neck reconstruction

Outcome Measures

Primary Outcomes (1)

• Clinical Parameters

  Clinical assessment. Assessment of Continent Score. Maximum dry interval per day.

  12 Weeks

Secondary Outcomes (1)

• Clinical Changes In Bladder Behavior

  24 Weeks

Study Arms (1)

Myoblasts Preparation

EXPERIMENTAL

Myoblast Preparation, Myoblast Transplantation \& Neonatal Cystourethroscope Injection Approximately 8 to 10 gm muscle will be obtained from the rectus abdominis. Patient muscle fibers will be isolated using the fiber explant technique described by Rosenblatt et al, with some modifications. Culture conditions will be mainly adapted from Rando and Blau. After 22 days of culture myoblasts will be harvested by trypsinization and incubated in serum-free medium during the last 2 hours before injection. Immediately before injection the cell pellet will be resuspended in autologous serum and/ or platelet rich plasma (PRP).

Procedure: Myoblast Transplantation; Biological: Neonatal Cystourethroscope Injection

Interventions

Myoblast Transplantation PROCEDURE

For each patient 4-7 Million cells per ml will be injected into 8 to 10 sites through a cystoscopic injection needle with a 10 mm long, 21 gauge needle connected to a 30 cm long plastic tube, using a 6.75Fr neonatal cystourethroscope. The suspension will be injected in the area of the external sphincter and along the posterior urethra proximal to the verumontanum, aiming to attain visual occlusion of the urethral lumen.

Myoblasts Preparation

Neonatal Cystourethroscope Injection BIOLOGICAL

4-7 Million cells per ml will be injected into 8 to 10 sites through a cystoscopic injection needle with a 10 mm long, 21 gauge needle connected to a 30 cm long plastic tube, using a 6.75Fr neonatal cystourethroscope.

Myoblasts Preparation

Eligibility Criteria

• Age: 2 Years - 10 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gender: male.
• Ages: above 2 Years old.
• Patient with Urinary incontinence after successful staged repair and bladder neck reconstruction of extrophy -epispadias complex.
• Absence of urinary tract infection after urine analysis and urine culture.
• Serum creatinine in normal range for age.
• Parent or legal guardian agrees to complete and sign the informed consent document.

You may not qualify if:

• Any degree of Spinal cord injury, systemic, neuronal paralysis or sacral agenesis.
• Urodynamic study demonstrating severe uninhibited bladder contractions.
• Severe urethral or bladder neck stricture demonstrated during screening cystoscopy or cystogram
• Cystography at the time of screening demonstrating Grade IV vesicoureteral reflux (high-grade reflux with dilation of the renal pelvis and blunting or the fornices) or Grade V vesicoureteral reflux (Grade IV findings plus loss of the papillary impression and ureteral tortuosity).
• Any degree of renal scarring at the time of screening as demonstrated by DMSA or MAG3 renal scintigraphy in the presence of any grade of vesicoureteral reflux (VUR)
• Renal ultrasound demonstrating Society of Fetal Urology Grade III hydronephrosis (widely split renal pelvis, renal calices uniformly dilated, no parenchymal thinning) or Grade IV hydronephrosis (Grade III dilation plus parenchymal thinning).
• Positive urine culture resistant to preoperative oral antibiotic therapy. Immunocompromise patient.
• Previous adverse reaction to anesthesia

Sponsors & Collaborators

• Al-Azhar University: lead
• Cairo University: collaborator
• Affiliated Hospital to Academy of Military Medical Sciences: collaborator

Study Sites (1)

Pediatric Surgery Outpatients Clinics - Al Hussien Hospital

Madīnat an Naşr, Cairo Governorate, Egypt

RECRUITING

MeSH Terms

Conditions

Urinary Incontinence; Bladder Exstrophy

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urogenital Abnormalities; Urinary Bladder Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Abdel-Wahab El-Okby, MD

  Deaprtment of Pediatric Surgery School of Medicine Al Azhar University

  PRINCIPAL INVESTIGATOR

• Abd-Elmoneim Shawky Shams El-deen, MD

  Department of Pediatric Surgery , School of Medicine, Al Azhar University

  STUDY CHAIR

• Hussein Galal, MD

  Department of Urology, School of Medicine, Al Azhar University

  STUDY CHAIR

• Sayed Bakry, PhD

  Laboratory of Molecular Biology , School of Science, Al Azhar University

  STUDY DIRECTOR

• Hala Gabr, MD

  Department of Clinical Pathology , School of Medicine, Al Azhar University

  STUDY CHAIR

• Wael Abu El Khier, MD

  Department of Clinical Pathology and Immunology, Military Academy

  STUDY CHAIR

• Ahmed Said Sayed Bayomy, MSc

  Department of Pediatric Surgery, School of Medicine, Al Azhar University

  STUDY CHAIR

Central Study Contacts

Abdel-Wahab El-Okby, MD

CONTACT

+201001478100

Hussein Galal, MD

CONTACT

+201001418597

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor , Consultant of Isolation and Culturing of Stem Cells

Study Record Dates

• First Submitted: February 26, 2014
• First Posted: March 3, 2014
• Study Start: December 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2016
• Last Updated: March 3, 2014

Record last verified: 2014-02

Locations

EG (1)