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Transurethral Myoblast Injection for Urinary Incontinence in Children With Bladder Exstrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02075216
Recruitment Status : Unknown
Verified February 2014 by Sayed Bakry, Al-Azhar University.
Recruitment status was:  Recruiting
First Posted : March 3, 2014
Last Update Posted : March 3, 2014
Sponsor:
Collaborators:
Cairo University
Affiliated Hospital to Academy of Military Medical Sciences
Information provided by (Responsible Party):
Sayed Bakry, Al-Azhar University

Tracking Information
First Submitted Date  ICMJE February 26, 2014
First Posted Date  ICMJE March 3, 2014
Last Update Posted Date March 3, 2014
Study Start Date  ICMJE December 2013
Estimated Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2014)
Clinical Parameters [ Time Frame: 12 Weeks ]
Clinical assessment. Assessment of Continent Score. Maximum dry interval per day.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2014)
Clinical Changes In Bladder Behavior [ Time Frame: 24 Weeks ]
Urodynamic Evaluation
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Transurethral Myoblast Injection for Urinary Incontinence in Children With Bladder Exstrophy
Official Title  ICMJE Transurethral Autologous Myoblast Injection for Treatment of Urinary Incontinence in Children With Bladder Exstrophy
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.

Detailed Description

Achieving urinary continence in patients with bladder extrophy epispadias complex remains a challenging urological goal. Children with bladder extrophy epispadias complex generally undergo many surgical procedures for the treatment of sphincteric incompetence, including bladder neck reconstruction, slings and bulking agent injection. The key point in most of these procedures is to enhance urethral resistance, leading to some degree of bladder outlet obstruction. However, the reported 7% to 85% continence rates in these patients may not exactly represent those children who achieve volitional voiding through the urethra, but may also include the ones with bladder augmentation and urinary diversion. Endoscopic injection of bulking agent has emerged as a therapeutic approach in the treatment of urinary incontinence (UI). this procedure seems to be economical, with shorter hospitalization and fewer major complications. On the other hand, degradation, migration, reabsorption, overbulking, bladder outlet obstruction and hypersensitivity are frequently reported complications of bulking agents.

The ideal substance for periurethral injection should be durable, non immunogenic, nonmigratory and efficacious. So, 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. Patients with incontinence usually have decreased resting tone and contractility of the rhabdosphincter. In patients with bladder extrophy epispadias complex the perineal structures are dislocated laterally, and the internal and external urethral sphincters are deficient. 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. After injury or in response to intensive physical exercise satellite cells proliferate and differentiate into myoblasts, which ultimately fuse to form new myofibers capable of muscle contraction. Considering the limited capacity of the rhabdosphincter for regeneration, the idea of urethral sphincter repair in patients with bladder extrophy epispadias COMPLEX via transurethral injection of autologous myoblasts has been suggested. The technical availability of these cells, as well as immunological acceptance and survival, makes them appropriate for this purpose. Satellite cells are committed cell lineage with restricted plasticity and do not multiply beyond the required repair needs. This property confers an acceptable measure of safety for clinical applications. The first clinical study 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urinary Incontinence
Intervention  ICMJE
  • Procedure: Myoblast Transplantation
    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.
  • Biological: Neonatal Cystourethroscope Injection
    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.
Study Arms  ICMJE Experimental: Myoblasts Preparation

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).

Interventions:
  • Procedure: Myoblast Transplantation
  • Biological: Neonatal Cystourethroscope Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 27, 2014)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2016
Estimated Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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.

-

Exclusion Criteria:

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

-

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 2 Years to 10 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Egypt
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02075216
Other Study ID Numbers  ICMJE NCT1502231
Azhar2013298 ( Other Identifier: Al Azhar University )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sayed Bakry, Al-Azhar University
Study Sponsor  ICMJE Al-Azhar University
Collaborators  ICMJE
  • Cairo University
  • Affiliated Hospital to Academy of Military Medical Sciences
Investigators  ICMJE
Principal Investigator: Abdel-Wahab El-Okby, MD Deaprtment of Pediatric Surgery School of Medicine Al Azhar University
Study Chair: 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 Director: Sayed Bakry, PhD Laboratory of Molecular Biology , School of Science, Al Azhar University
Study Chair: 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
PRS Account Al-Azhar University
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP