Urinary Incontinence, Urinary Retention
Conditions
Keywords
Underactive Bladder
Brief summary
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
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.
Interventions
BIOLOGICALAutologous Muscle Derived Cells
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.
Sponsors
Jason Gilleran
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females, at least 18 years of age 2. History of Underactive Bladder (UAB) for at least 6 months documented in the medical record 3. Recurring UAB symptoms 4. Subjects unresponsive to relief symptoms of UAB with previous use of medications and/or other treatments 5. Voiding difficulty (complains of difficulty emptying the bladder) 6. Post void residual greater than or equal to 150 mL 7. Total UAB Questionnaire Score greater than or equal to 3 8. Females of child-bearing potential agree to use a reliable form of birth control for the entire study duration 9. 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
1. Pregnant, plans to become pregnant or lactating 2. History of bleeding diathesis, uncorrectable coagulopathy, or would refuse a blood transfusion 3. Currently on anticoagulant therapy 4. Obvious neurological impairment 5. Known allergy or hypersensitivity to bovine proteins or allergens, gentamicin sulfate, ampicillin, and/or lidocaine that medically warrants exclusion as determined by the physician 6. 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 7. Has been treated with an investigational device, drug, or procedure for UAB within the last 6 months. 8. 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) 9. History of cancer in pelvic organs, ureters, or kidneys or any cancer that has undergone treatment within the past 12 months 10. Compromised immune system due to disease state, chronic corticosteroid use, or other immunosuppressive therapy 11. History of radiation therapy to the bladder 12. 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 13. Abnormal renal function 14. An active urinary tract infection as evidenced by positive urine culture 15. 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 16. Requires concomitant use of or treatment with immunosuppressive agents 17. Pelvic organ prolapse beyond the introitus (e.g., cystocele, rectocele) 18. Abnormal bladder capacity (i.e., less than 100 mL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Study-related Adverse Events at 6 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | 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. |
| Change in Incontinence Questionnaire (ICIQ) Long Form Score From Baseline at 12 Months. | 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. |
| Change in Underactive Bladder Questionnaire (UABQ) Score From Baseline at 12 Months | 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. |
| The Change in Number of Independent Voiding Occurrences Per Day on the 3-day Bladder Diary From Baseline at 12 Months. | 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. |
| Number of Participants With Study-related Adverse Events Between 6 and 12 Months | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous Muscle Derived Cells 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.
Autologous Muscle Derived Cells: 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. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 12 Months Through End of Study | Lost to Follow-up | 1 |
| 6 Months Through 12 Months | Lost to Follow-up | 1 |
| 6 Months Through 12 Months | Withdrawal by Subject | 1 |
| Enrollment Through 6 Months | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Autologous Muscle Derived Cells |
|---|---|
| Age, Continuous | 61.45 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 4 / 20 |
Outcome results
Primary
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.
Time frame: 6 months
Population: Participants may have reported more than one AE during this study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events at 6 Months | Bruise | 2 participants |
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events at 6 Months | Pain | 1 participants |
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events at 6 Months | Scrotum discomfort | 1 participants |
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events at 6 Months | Scrotum swelling | 1 participants |
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events at 6 Months | Urinary tract infection | 1 participants |
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events at 6 Months | Vasovagal response | 1 participants |
Secondary
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.
Time frame: 12 months
Population: 17 subjects remaining in the study at 12 months had data analyzed for this outcome: 3 female and 14 male.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Muscle Derived Cells | Change in Incontinence Questionnaire (ICIQ) Long Form Score From Baseline at 12 Months. | Female (ICIQ-FLUTS) long form | 0.6667 units on a scale | Standard Deviation 5.1 |
| Autologous Muscle Derived Cells | Change in Incontinence Questionnaire (ICIQ) Long Form Score From Baseline at 12 Months. | Male (ICIQ-MLUTS) long form | 1.071 units on a scale | Standard Deviation 9.6 |
Secondary
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.
Time frame: 12 months
Population: 17 subjects remaining at 12 months submitted data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous Muscle Derived Cells | Change in Underactive Bladder Questionnaire (UABQ) Score From Baseline at 12 Months | 5.7 score on a scale | Standard Deviation 2.7 |
Secondary
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.
Time frame: 12 months
Population: 17 subjects remaining in study at 12 months submitted data for analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | No change | 5 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Markedly Improved | 0 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Moderately improved | 3 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Slightly improved | 9 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Slightly worse | 0 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Moderately worse | 0 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Markedly worse | 0 Participants |
Secondary
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.
Time frame: 12 months
Population: 17 subjects remaining in study at 12 months submitted data for analysis
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Very much better | 0 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Much better | 3 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | A little bit better | 9 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | No change | 5 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | A little worse | 0 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Much worse | 0 Participants |
| Autologous Muscle Derived Cells | Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months. | Very much worse | 0 Participants |
Secondary
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.
Time frame: Between 6 and 12 months
Population: Subjects may have reported more than one adverse event during this study period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events Between 6 and 12 Months | Urine leakage | 1 participants |
| Autologous Muscle Derived Cells | Number of Participants With Study-related Adverse Events Between 6 and 12 Months | Bleeding at site of injection | 1 participants |
Secondary
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.
Time frame: 12 months
Population: 10 subjects had data available for both timepoints
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous Muscle Derived Cells | The Change in Number of Independent Voiding Occurrences Per Day on the 3-day Bladder Diary From Baseline at 12 Months. | -0.665 number of voids/day | Standard Deviation 5.3 |
Secondary
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.
Time frame: 12 months
Population: 14 subjects had data for both timepoints
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous Muscle Derived Cells | 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. | -894.9 milliliters/day | Standard Deviation 2100 |
Secondary
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.
Time frame: 12 months
Population: 10 subjects had data reported for both timepoints
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous Muscle Derived Cells | 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. | -156.66 milliliters/day | Standard Deviation 1100 |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous Muscle Derived Cells | 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. | 0 bladder leaks per day | Standard Deviation 0 |
Secondary
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.
Time frame: 12 months
Population: 19 subjects had data reported for both timepoints
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous Muscle Derived Cells | 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. | -0.2094 number of voids/day | Standard Deviation 1.6 |