Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence

• Status: Terminated
• Trial end date: 2020-01-23
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University

Criteria

Inclusion Criteria:

1. 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.

2. 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.

3. 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.

4. 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.

5. Parent or legal guardian able to complete and sign the informed consent document.

6. 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.

Exclusion Criteria:

1. Urodynamic study demonstrating severe uninhibited bladder contractions.

2. Severe urethral or bladder neck stricture demonstrated during screening cystoscopy or cystogram

3. 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).

4. 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)

5. 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.

6. Previous injection of bulking agents at the level of the bladder neck (bovine collagen or DEFLUX™)

7. Positive urine culture resistant to preoperative oral antibiotic therapy

8. Need for chronic or pulse steroids or history of other congenital or acquired condition that results in immunocompromise

9. Previous adverse reaction to anesthesia