Transurethral Myoblast Injection for Urinary Incontinence in Children With Bladder Exstrophy
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|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
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.
|Condition or disease||Intervention/treatment||Phase|
|Urinary Incontinence||Procedure: Myoblast Transplantation Biological: Neonatal Cystourethroscope Injection||Phase 1 Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Transurethral Autologous Myoblast Injection for Treatment of Urinary Incontinence in Children With Bladder Exstrophy|
|Study Start Date :||December 2013|
|Estimated Primary Completion Date :||November 2015|
|Estimated Study Completion Date :||December 2016|
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).
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.
- Clinical Parameters [ Time Frame: 12 Weeks ]
Assessment of Continent Score.
Maximum dry interval per day.
- Clinical Changes In Bladder Behavior [ Time Frame: 24 Weeks ]Urodynamic Evaluation
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): NCT02075216
|Contact: Abdel-Wahab El-Okby, MD||+201001478100|
|Contact: Hussein Galal, MD||+201001418597|
|Pediatric Surgery Outpatients Clinics - Al Hussien Hospital||Recruiting|
|Nasr City, Cairo, Egypt|
|Contact: Ahmed Saied, MSc +201272453475 firstname.lastname@example.org|
|Sub-Investigator: Ahmed Saied Sayed Bayomy, MSc|
|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|