Bladder ExstrophyPhase 1MDCNCT01011777
Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence
A Phase 1 study testing MDC in people with Bladder Exstrophy and Urinary Incontinence, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Bladder Exstrophy, Urinary Incontinence
- What is being tested?
- MDC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2017to 23 Jan 2020
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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™)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brady Urological Institute. Johns Hopkins University
Baltimore, Maryland, 21287
About this study
Official title: Phase I Study of Endoscopically Injected Muscle Derived Cells in Participants With Exstrophy-epispadias Complex Related Urinary Incontinence
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.
Read the detailed description
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
- Conditions
- Bladder Exstrophy, Urinary Incontinence
- Being tested
- MDC
- Keywords
- bladder exstrophy epispadias complex, urinary incontinence, muscle derive cell therapy, stem cells
- Medical subject headings
- Bladder Exstrophy, Urinary Incontinence, Bladder Exstrophy and Epispadias Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MDCDrug
Also called Autologous Muscle Derived Cells
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MDC |
What is being measured
The primary outcome is the main question the study is designed to answer.
The ability to inject the MDC product in a safe and tolerable manner in a clinical setting using a descriptive approach.
Measured: 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.
Measured: Monthly voiding diary. All other parameters measure at baseline and every 6 months for 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2009 (estimated)
- Study start1 Feb 2017
- Primary completion23 Jan 2020
- Study completion23 Jan 2020
Why it stopped: Due to participants withdrawal prior to anticipated end of study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder ExstrophyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John P Gearhart, MD, Principal investigator, Brady Urological Institute, Department of Pediatric Urology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01011777
- Sponsor's protocol ID
- IRB00061692
- Acronym
- MDC
- Status last verified
- Jan 2020
- First submitted
- 10 Nov 2009
- Last updated
- 28 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Endoscopically Injected Muscle Derived Cells in Participants With Exstrophy-epispadias Complex Related Urinary Incontinence
- ClinicalTrials.gov ID
- NCT01011777
- Acronym / sponsor ID
- MDC / IRB00061692
- Conditions
- Bladder Exstrophy, Urinary Incontinence
- Keywords
- bladder exstrophy epispadias complex, urinary incontinence, muscle derive cell therapy, stem cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to participants withdrawal prior to anticipated end of study.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 23 Jan 2020 (actual)
- Study completion
- 23 Jan 2020 (actual)
- First posted
- 11 Nov 2009 (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.
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.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous Muscle Derived Cells | Experimental | Drug: MDCSurgeon 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Group 1 - Males and females at least 2 years of age with:
- Group 2 - Males and females greater than 5 years of age with:
- Screening labs obtained less than 30 days prior to MDC injection meeting the following criteria:
- 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.
Key exclusion criteria (9 listed)
- 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.
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 |
|---|---|---|
| MDCAlso: Autologous Muscle Derived CellsAfter 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. | Drug | Autologous Muscle Derived Cells |
Primary outcome
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
1 secondary outcome
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.
Results and safety
The study was stopped early (reason given: Due to participants withdrawal prior to anticipated end of study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
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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.
John P Gearhart, MD principal investigator
Brady Urological Institute, Department of Pediatric Urology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MDC in people with Bladder Exstrophy and Urinary Incontinence, run by Johns Hopkins University at 1 site in United States.
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 14 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: stopped early, as of the sponsor's last update on 28 Jan 2020. 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 United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to participants withdrawal prior to anticipated end of study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 28 Jan 2020.