Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence (MDC)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Protocol to Study the Safety and Tolerability of Endoscopic Injection of Autologous Muscle Derived Cells (MDC) in Children With Exstrophy-epispadias Complex Related Urinary Incontinence|
- The ability to inject the MDC product in a safe and tolerable manner in a clinical setting using a descriptive approach. [ Time Frame: Post op day 1, day 40, monthly afterwards for 36 months ] [ Designated as safety issue: Yes ]
- changes in urinary incontinence levels and bladder growth in enrolled participants after undergoing autologous MDC injection using cystograms, urodynamic studies, 24-hour pad weight test, continence score, and maximum day & nighttime dry interval. [ Time Frame: Monthly voiding diary. All other parameters measure at baseline and every 6 months for 36 months. ] [ Designated as safety issue: No ]
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Autologous Muscle Derived Cells
Surgeon will endoscopically inject previously harvested autologous muscle derived cells (MDC) into the same bladder exstrophy patient's urinary sphincter to improve outflow resistance and rhabdosphincter contractility. We will assess tolerability and induction of continence.
After the biopsy the MDC expansion process takes approximately 21 days after which cells are harvested and cryopreserved for future injection. The MDC product is stored in single use vials, with each vial containing approximately 2.6 x 10^7 total cells. The volume of each vial will be 1.3ml. This study uses a single dose of approximately 2.0 x 10^7 cells administered endoscopically into the external urethral sphincter in 12 injections of 0.1ml each. Six months post-initial MDC injection, group 1 participants with persistent bladder capacity less than 100cc and group 2 participants with persistent urinary incontinence as defined in eligibility criteria may undergo repeat injections of MDC at 6 month intervals for up to a total of 4 injections.
Other Name: Autologous Muscle Derived Cells
Bladder exstrophy patients who have undergone primary bladder closure, but have a bladder capacity too low for bladder neck reconstruction (Group 1), have limited additional surgical options that permits urethral voiding and urine storage within a native bladder. Previous studies have demonstrated a positive correlation between bladder capacity and success of bladder neck reconstruction. Likewise, patients who have undergone bladder neck reconstruction but continue to have urinary incontinence (Group 2) are also faced with limited options. Often, both groups are considered for augmentation cystoplasty with closure of the bladder neck requiring intermittent catheter voiding through a surgically constructed continent catheterizable channel. Such major reconstruction has significant associated short and long-term morbidities. Endoscopic injection of MDCs for the treatment of urinary sphincter insufficiency is a potential alternative therapy for these patients. By increasing the outflow resistance and rhabdosphincter contractility, MDC injection may permit more efficient bladder cycling and bladder expansion in Group 1 patients allowing them to proceed on to bladder neck reconstruction. This same increase in resistance and sphincter contractility may allow Group 2 patients to attain urinary continence and avoid any further reconstructive surgical procedures.
Eligible and consented patients would undergo rectus muscle biopsy and immediately transferred to the Cell Therapy Lab for tissue processing and MDC expansion.The MDC expansion process takes approximately 21 days after which cells are harvest and cryopreserved for future injection.Each vial will be filled with cells at a concentration of approximately 2.0 x 107 cells/ml. At the time of planned MDC injection, enrolled patients will return for cystoscopy under anesthesia. At that time, aliquots of MDCs will be removed from the freezer and be allowed to thaw passively in the 30 minutes preceding the time of planned injection. MDC product will be endoscopically injected using an FDA approved DEFLUX™ needle at the level of the external urethral rhabdosphincter and bladder neck. Patients would be assessed for toxicity and adverse events postoperatively at day 1 and 40 followed by semiannual visits for 36 months. variables measured are:
group 1: Bladder capacity, detrusor leak point pressure, bladder filling pressure, post-void residual urine volume, urodynamics, periurethral electromyographic activity, renal - Bladder Ultrasound, cystoscopy.
Group 2: Detrusor leak point pressure, bladder filling pressure, maximum cystometric capacity, post-void residual urine volume, periurethral electromyographic activity, 24 hour pad / diaper weight assessment, voiding diary including incontinence grade and maximum daytime dry interval, renal - Bladder Ultrasound, cystoscopy
Please refer to this study by its ClinicalTrials.gov identifier: NCT01011777
|Contact: John P Gearhart, MD||(410) 955-5358||Jgearhart@jhmi.edu|
|United States, Maryland|
|Brady Urological Institute. Johns Hopkins University||Not yet recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: John P Gearhart, MD 410-955-5358 Jgearhart@jhmi.edu|
|Principal Investigator: John P Gearhart, MD|
|Principal Investigator:||John P Gearhart, MD||Brady Urological Institute, Department of Pediatric Urology|