Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence

NCT01011777 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IRB00061692
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to study safety, tolerability and efficacy of muscle derived cell (MDC) therapy in children with bladder exstrophy epispadias induced urinary incontinence.

Conditions

Bladder Exstrophy; Urinary Incontinence

Keywords

bladder exstrophy epispadias complex; urinary incontinence; muscle derive cell therapy; stem cells

Outcome Measures

Primary Outcomes (1)

• The ability to inject the MDC product in a safe and tolerable manner in a clinical setting using a descriptive approach.

  Post op day 1, day 40, monthly afterwards for 36 months

Secondary Outcomes (1)

• 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.

  Monthly voiding diary. All other parameters measure at baseline and every 6 months for 36 months.

Study Arms (1)

Autologous Muscle Derived Cells

EXPERIMENTAL

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.

Drug: MDC

Interventions

MDC DRUG

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.

Also known as: Autologous Muscle Derived Cells

Autologous Muscle Derived Cells

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1 - Males and females at least 2 years of age with:
• Classic bladder exstrophy with successful primary, secondary, or delayed primary closure and subsequent epispadias repair.
• Cystography done with 90 days preceding participant identification and at least 12 months after successful bladder closure demonstrating a bladder capacity less than 100cc.
• Group 2 - Males and females greater than 5 years of age with:
• Classic bladder exstrophy with successful primary, secondary, or delayed primary closure and subsequent epispadias repair.
• Previous bladder neck reconstruction.
• At the time of participant identification, urinary incontinence defined as leakage of urine at night or leakage of urine at an interval of less than 3 hours in the daytime persisting at least 2 years after bladder neck reconstruction.
• Screening labs obtained less than 30 days prior to MDC injection meeting the following criteria:
• Urinalysis and urine culture demonstrating either no bacterial growth or growth of an organism that can be treated with an appropriate oral antibiotic for 7 days preoperatively. Participants with a positive urine culture should have the urinalysis and urine culture repeated after completion of antibiotics and prior to MDC injection. A negative urine culture must be demonstrated prior to MDC injection.
• Serum creatinine in normal range for age (Infant: 0.2-0.4 mg/dl; Child 0.3-0.7 mg/dl; Adolescent 0.5-1.0 mg/dl).
• Negative Study Donor Virology Panel (Hep B surface antigen, HIV 1 / 2 antibody, Hep B core antibody, Rapid Plasma Reagin (RPR), Human T-cell Lymphotrophic Virus (HTLV) I / II antibody, Hep C antibody). This panel is only done during the screening process and is not repeated during study follow-up.
• Parent or legal guardian who is, in the opinion of the investigator, reliable and willing to make themselves and patient available for the duration of the study and are willing to follow study procedures and unit policies.
• Parent or legal guardian able to complete and sign the informed consent document.
• Negative pregnancy test for sexual active female teenagers. If able to conceive and sexually active, participants must agree to use barrier contraceptives from the time of study enrollment until 6 months after the last MDC injection. Male participants who are able to conceive and are sexually active must agree to use protection as well from the time of study enrollment until 6 months after the last MDC injection.

You may not qualify if:

• 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). See Appendix D.
• Previous injection of bulking agents at the level of the bladder neck (bovine collagen or DEFLUX™)
• Positive urine culture resistant to preoperative oral antibiotic therapy
• Need for chronic or pulse steroids or history of other congenital or acquired condition that results in immunocompromise
• Previous adverse reaction to anesthesia

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Brady Urological Institute. Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Bladder Exstrophy; Urinary Incontinence; Bladder Exstrophy and Epispadias Complex

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• John P Gearhart, MD

  Brady Urological Institute, Department of Pediatric Urology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2009
• First Posted: November 11, 2009
• Study Start: February 1, 2017
• Primary Completion: January 23, 2020
• Study Completion: January 23, 2020
• Last Updated: January 28, 2020

Record last verified: 2020-01

Locations

US (1)