Urinary IncontinencePhase 1/2NCT02075216
Transurethral Myoblast Injection for Urinary Incontinence in Children With Bladder Exstrophy
A Phase 1/2 study testing Myoblast Transplantation and Neonatal Cystourethroscope Injection in people with Urinary Incontinence, run by Al-Azhar University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 10 years, men only
- Conditions the study is for
- Urinary Incontinence
- What is being tested?
- Myoblast Transplantation and Neonatal Cystourethroscope Injection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteEgypt
- Study dates
- Dec 2013to Dec 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 10 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- 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.
- -
Who cannot join
- 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).
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- Positive urine culture resistant to preoperative oral antibiotic therapy. Immunocompromise patient.
- Previous adverse reaction to anesthesia
- -
Trial locations and contacts
1 site in 1 country.
Abdel-Wahab El-Okby, MD contact
Hussein Galal, MD contact
Egypt1 site, 1 recruiting
- Recruiting
Pediatric Surgery Outpatients Clinics - Al Hussien Hospital
Madīnat an Naşr, Cairo Governorate
Ahmed Saied, MSc, +201272453475, drahmedsaid.clinic@yahoo.com
Ahmed Saied Sayed Bayomy, MSc
About this study
Official title: Transurethral Autologous Myoblast Injection for Treatment of Urinary Incontinence in Children With Bladder Exstrophy
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.
Read the 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.
- Conditions
- Urinary Incontinence
- Being tested
- Myoblast Transplantation, Neonatal Cystourethroscope Injection
- Keywords
- Urinary Incontinence, Children, Bladder Exstrophy, Extrophy -Epispadias complex,, Modern staged repair,, Bladder neck reconstruction
- Medical subject headings
- Urinary Incontinence, Bladder Exstrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Myoblast TransplantationProcedure or surgery
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.
Neonatal Cystourethroscope InjectionBiological
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 group | Role | What they receive |
|---|---|---|
| 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). Receives: Procedure: Myoblast Transplantation; Biological: Neonatal Cystourethroscope Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Parameters
Clinical assessment.
Assessment of Continent Score.
Maximum dry interval per day.
Measured: 12 Weeks
Secondary outcomes (1)
Clinical Changes In Bladder Behavior
Urodynamic Evaluation
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2014 (estimated)
- Study startDec 2013
- Primary completionNov 2015 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urinary IncontinenceStudies of the same condition, open and under way.
- More trials run by Al-Azhar UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Al-Azhar University
- Sponsor type
- University, hospital or other
- Collaborators
- Cairo University, Affiliated Hospital to Academy of Military Medical Sciences
- Responsible party
- Principal investigator, Sayed Bakry, Al-Azhar University
- Investigators
- Abdel-Wahab El-Okby, MD, Principal investigator, Deaprtment of Pediatric Surgery School of Medicine Al Azhar UniversityAbd-Elmoneim Shawky Shams El-deen, MD, Study chair, Department of Pediatric Surgery , School of Medicine, Al Azhar UniversityHussein Galal, MD, Study chair, Department of Urology, School of Medicine, Al Azhar UniversitySayed Bakry, PhD, Study director, Laboratory of Molecular Biology , School of Science, Al Azhar UniversityHala Gabr, MD, Study chair, Department of Clinical Pathology , School of Medicine, Al Azhar UniversityWael Abu El Khier, MD, Study chair, Department of Clinical Pathology and Immunology, Military AcademyAhmed Said Sayed Bayomy, MSc, Study chair, Department of Pediatric Surgery, School of Medicine, Al Azhar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02075216
- Sponsor's protocol ID
- NCT1502231
- Other IDs
- Azhar2013298
- Status last verified
- Feb 2014
- First submitted
- 26 Feb 2014
- Last updated
- 3 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transurethral Autologous Myoblast Injection for Treatment of Urinary Incontinence in Children With Bladder Exstrophy
- ClinicalTrials.gov ID
- NCT02075216
- Acronym / sponsor ID
- NCT1502231
- Conditions
- Urinary Incontinence
- Keywords
- Urinary Incontinence, Children, Bladder Exstrophy, Extrophy -Epispadias complex,, Modern staged repair,, Bladder neck reconstruction
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Al-Azhar UniversityUniversity, hospital or other
- Collaborators
- Cairo University, Affiliated Hospital to Academy of Military Medical Sciences
- Study start
- Dec 2013
- Primary completion
- Nov 2015 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 3 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Myoblasts Preparation | Experimental | Procedure: Myoblast Transplantation, Biological: Neonatal Cystourethroscope InjectionMyoblast 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). |
Who may qualify
- Ages
- 2 to 10 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Myoblast TransplantationFor 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. | Procedure or surgery | Myoblasts Preparation |
| Neonatal Cystourethroscope Injection4-7 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. | Biological | Myoblasts Preparation |
Primary outcome
Clinical Parameters
Time frame: 12 Weeks
Clinical assessment. Assessment of Continent Score. Maximum dry interval per day.
1 secondary outcome
Clinical Changes In Bladder Behavior
Time frame: 24 Weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abdel-Wahab El-Okby, MD contact
Hussein Galal, MD contact
Abdel-Wahab El-Okby, MD principal investigator
Deaprtment of Pediatric Surgery School of Medicine Al Azhar University
Abd-Elmoneim Shawky Shams El-deen, MD study chair
Department of Pediatric Surgery , School of Medicine, Al Azhar University
Hussein Galal, MD study chair
Department of Urology, School of Medicine, Al Azhar University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Myoblast Transplantation and Neonatal Cystourethroscope Injection in people with Urinary Incontinence, run by Al-Azhar University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Abdel-Wahab El-Okby, MD (+201001478100), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Parameters (time frame: 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2014.