Autologous Muscle Derived Cells for Underactive Bladder

Study Overview
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Brief Summary
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This is a prospective, open-label, Phase 1, single center study evaluating the safety and efficacy of Autologous Muscle Derived Cells as a treatment for chronic Underactive Bladder.

Detailed Description
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Subject that meet inclusion and exclusion criteria will be consented and enrolled in this study. Initial screening includes blood and urine testing, questionnaires, physical examination, specialized bladder function testing and review of medical history. At the next visit a small sample of each subject's own thigh muscle is obtained by needle biopsy. This cell biopsy is sent to a specialized lab for growth and processing. Approximately ten weeks later the frozen cells will be sent back to the treatment site for thawing, diluting and injection under lighted instrumentation into the subject's bladder wall. The subject will be followed for 6 months and at that time may be eligible for a second injection of cells. The study doctor will determine if the second injection may be beneficial to the subject. All subjects will be followed for up to 12 months. The follow-up assessments at 12 months will include questionnaires, urine and blood testing, specialized bladder function testing and visualizing the inside of the bladder with a lighted instrument.

Official Title
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Autologous Muscle Derived Cells for Underactive Bladder

Conditions
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Urinary Retention, Urinary Incontinence

Intervention / Treatment
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* Biological: Autologous Muscle Derived Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, at least 18 years of age History of Underactive Bladder (UAB) for at least 6 months documented in the medical record Recurring UAB symptoms Subjects unresponsive to relief symptoms of UAB with previous use of medications and/or other treatments Voiding difficulty (complains of difficulty emptying the bladder) Post void residual greater than or equal to 150 mL Total UAB Questionnaire Score greater than or equal to 3 Females of child-bearing potential agree to use a reliable form of birth control for the entire study duration Willing and capable of understanding and complying with all requirements of the protocol, including proper completion of the voiding diaries and self-administered questionnaires Exclusion Criteria: Pregnant, plans to become pregnant or lactating History of bleeding diathesis, uncorrectable coagulopathy, or would refuse a blood transfusion Currently on anticoagulant therapy Obvious neurological impairment Known allergy or hypersensitivity to bovine proteins or allergens, gentamicin sulfate, ampicillin, and/or lidocaine that medically warrants exclusion as determined by the physician Simultaneously participating in another investigational drug or device study or use of any investigational drug(s) or therapeutic device(s) within 3 months preceding enrollment Has been treated with an investigational device, drug, or procedure for UAB within the last 6 months. Medical condition or disorder that may limit life expectancy or that may cause protocol deviations (e.g. unable to perform self-evaluations and/or accurately report medical history, urinary symptoms, and/or data) History of cancer in pelvic organs, ureters, or kidneys or any cancer that has undergone treatment within the past 12 months Compromised immune system due to disease state, chronic corticosteroid use, or other immunosuppressive therapy History of radiation therapy to the bladder Tests positive for Hepatitis B (Hepatitis B Surface Antigen), and Anti-Hepatitis B Core Total Antibody, Hepatitis C (Anti-Hepatitis C virus enzyme immunoassay, Human Immunodeficiency Virus (HIV Type I and 2 Antibodies), and/or Syphilis Abnormal renal function An active urinary tract infection as evidenced by positive urine culture Taking medication(s) that affect urination (e.g. medically necessary, stable drugs) such as prescription drugs, over-the-counter drugs, or dietary supplements, including herbal supplements and those taken with teas Requires concomitant use of or treatment with immunosuppressive agents Pelvic organ prolapse beyond the introitus (e.g., cystocele, rectocele) Abnormal bladder capacity (i.e., less than 100 mL)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Muscle Derived Cells<br>Autologous Muscle Derived Cells are obtained by needle biopsy from the subject's own thigh muscle. These cells are sent to a special lab for growth and processing. When ready the cells are sent to the treatment location for injection into the bladder wall. | Biological: Autologous Muscle Derived Cells<br>* A small sample of the subject's own thigh muscle is obtained by needle biopsy. The biopsy sample is sent to Cook Myosite, Inc. for growth and processing. When the sample cell dosage is achieved the cells are frozen and sent back to the treatment site. The cells are thawed, diluted and injected under lighted instrumentation and visualization into about 30 sites in the bladder wall.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Study-related Adverse Events at 6 Months | Safety of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by occurrences of study-related adverse events (AEs) reported by 6 months after enrollment. Number of reports of each adverse event is listed for events determined to be definitely or possibly related to study activities. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Study-related Adverse Events Between 6 and 12 Months | Long term safety of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by occurrences of study-related adverse events (AEs) reported between 6 and 12 months after enrollment. Number of reports of each adverse event is listed for events determined to be definitely or possibly related to study activities. | Between 6 and 12 months | 
| Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject completed GRA questionnaire. The GRA measures the subjects perceived level of change in underactive bladder symptoms at 12 months compared to before they were treated. The scale ranges from: Markedly worse, Moderately worse, Slightly worse, No change, Slightly improved, Moderately improved, to Markedly improved. Subjects select one response. | 12 months | 
| Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported degree of change in urinary symptoms on the PGI-I at 12 months, compared to how their symptoms were before they began the study. Subjects select one response. The response scale ranges from: Very much better, Much better, A little bit better, No change, A little worse, Much worse, Very Much worse. | 12 months | 
| Change in Incontinence Questionnaire (ICIQ) Long Form Score From Baseline at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported urinary symptoms at 12 months from baseline. The ICIQ has a separate female (ICIQ-FLUTS Long form) and male (ICIQ-MLUTS long Form) set of questions to assess urinary symptoms in each sex. The total score range for ICIQ-FLUTS is 0-69. The total score range for ICIQ-MLUTS is 0-84. The sum of all the question scores equal a total score. Each question has a degree of bother scale associated with it. The degree of bother ranges from 0 (none at all) to 10 ( a great deal). Degree of bother scores are not incorporated in the overall score but indicate impact of the individual symptom. The difference taken in this analysis is the difference between the total score at 12 months minus the total score at baseline. If the difference is negative, it indicates improvement in the symptoms; 0 is no change; and a positive difference indicates a worsening of the symptoms. | 12 months | 
| Change in Underactive Bladder Questionnaire (UABQ) Score From Baseline at 12 Months | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by subject reported changes to urinary symptoms at 12 months from baseline on the UABQ. The UABQ is a set of questions to assess urinary symptoms associated with underactive bladder. The total score ranges between 0 to 16. A lower score indicates a better outcome. A higher score indicates a worse outcome. | 12 months | 
| The Change in Number of Independent Voiding Occurrences Per Day on the 3-day Bladder Diary From Baseline at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported number of independent daytime voiding occurrences per day on the 3-day diary at 12 months compared to baseline. Positive numbers reflect a larger number of independent voids per day reported at baseline, and negative number represent a larger number of independent voids per day reported at 12 months. | 12 months | 
| The Change in the Number of Voiding Occurrences Per Day Using a Catheter Recorded on the 3-day Bladder Diary From Baseline at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported number of daytime voiding occurrences per day using a catheter on the 3-day diary at 12 months compared to baseline. Positive numbers reflect a larger number of voiding occurrences per day reported at baseline, and negative numbers represent a larger number of voiding occurrences per day reported at 12 months. | 12 months | 
| The Change in the Average Volume Voided Independently Per Day Measured in Milliliters Over the 3 Day Period Recorded on the 3-day Bladder Diary From Baseline at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported average volume voided independently per day over the 3 day period on the 3-day diary at 12 months compared to baseline. Volumes are measured in milliliters. Positive numbers reflect a larger volume voided per day at baseline, and negative numbers represent a larger volume voided per day at 12 months. | 12 months | 
| The Change in the Average Volume in Milliliters Voided Per Day Using a Catheter Per Day Over the 3 Day Period Recorded on the 3-day Bladder Diary From Baseline at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported average volume voided using a catheter per day over the 3 day period on the 3-day diary at 12 months compared to baseline. Volumes are measured in milliliters. Positive numbers reflect a larger volume voided per day at baseline, and negative numbers represent a larger volume voided per day at 12 months. | 12 months | 
| The Change in the Number of Bladder Leaks Over the 3 Day Period Recorded on the 3-day Bladder Diary From Baseline at 12 Months. | The efficacy of Autologous Muscle Derived Cells in the treatment of underactive bladder as measured by changes to subject reported number of bladder leaks over the 3 day period on the 3-day diary at 12 months compared to baseline. Positive numbers reflect a larger number of leaks reported at baseline, and negative numbers represent a larger number of leaks reported at 12 months. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Underactive Bladder