ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.


Condition or disease Intervention/treatment Phase
Urinary Incontinence Procedure: Myoblast Transplantation Biological: Neonatal Cystourethroscope Injection Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. Clinical Parameters [ Time Frame: 12 Weeks ]

    Clinical assessment.

    Assessment of Continent Score.

    Maximum dry interval per day.



Secondary Outcome Measures :
  1. Clinical Changes In Bladder Behavior [ Time Frame: 24 Weeks ]
    Urodynamic Evaluation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years to 10 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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


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): NCT02075216


Contacts
Contact: Abdel-Wahab El-Okby, MD +201001478100
Contact: Hussein Galal, MD +201001418597

Locations
Egypt
Pediatric Surgery Outpatients Clinics - Al Hussien Hospital Recruiting
Nasr City, Cairo, Egypt
Contact: Ahmed Saied, MSc    +201272453475    drahmedsaid.clinic@yahoo.com   
Sub-Investigator: Ahmed Saied Sayed Bayomy, MSc         
Sponsors and Collaborators
Al-Azhar University
Cairo University
Affiliated Hospital to Academy of Military Medical Sciences
Investigators
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

Responsible Party: Sayed Bakry, Associate Professor , Consultant of Isolation and Culturing of Stem Cells, Al-Azhar University
ClinicalTrials.gov Identifier: NCT02075216     History of Changes
Other Study ID Numbers: NCT1502231
Azhar2013298 ( Other Identifier: Al Azhar University )
First Posted: March 3, 2014    Key Record Dates
Last Update Posted: March 3, 2014
Last Verified: February 2014

Keywords provided by Sayed Bakry, Al-Azhar University:
Urinary Incontinence
Children
Bladder Exstrophy
Extrophy -Epispadias complex,
Modern staged repair,
Bladder neck reconstruction

Additional relevant MeSH terms:
Urinary Incontinence
Enuresis
Bladder Exstrophy
Urination Disorders
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Behavioral Symptoms
Elimination Disorders
Mental Disorders
Urogenital Abnormalities
Urinary Bladder Diseases
Congenital Abnormalities