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CompletedNCT02463448Updated Jan 19, 2022Results posted

Autologous Muscle Derived Cells for Underactive Bladder

A Phase 1 interventional study of Autologous Muscle Derived Cells in Urinary Retention and Urinary Incontinence, sponsored by Jason Gilleran. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-01-19.

Sponsored by Jason Gilleran · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
23
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Urinary Retention
  • Urinary Incontinence

Keywords

  • Underactive Bladder
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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)
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
23 participants (actual)

Study arms

  • Experimental
    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.

    Biological: Autologous Muscle Derived Cells

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.

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

06

Results

Posted Jan 19, 2022

Participant flow

Enrollment Through 6 Months
Participant flow — Enrollment Through 6 Months
MilestoneAutologous Muscle Derived Cells
Started23
Completed20
Not completed3
Withdrew: Withdrawal by subject3
6 Months Through 12 Months
Participant flow — 6 Months Through 12 Months
MilestoneAutologous Muscle Derived Cells
Started20
Completed18
Not completed2
Withdrew: Lost to follow-up1
Withdrew: Withdrawal by subject1
12 Months Through End of Study
Participant flow — 12 Months Through End of Study
MilestoneAutologous Muscle Derived Cells
Started18
Completed17
Not completed1
Withdrew: Lost to follow-up1

Outcome measures

PrimaryNumber 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
Reported as:
Number · participants
Number of Participants With Study-related Adverse Events at 6 Months
participantsAutologous Muscle Derived Cells
Bruise2
Pain1
Scrotum discomfort1
Scrotum swelling1
Urinary tract infection1
Vasovagal response1
SecondaryNumber 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
Reported as:
Number · participants
Number of Participants With Study-related Adverse Events Between 6 and 12 Months
participantsAutologous Muscle Derived Cells
Urine leakage1
Bleeding at site of injection1
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months.
ParticipantsAutologous Muscle Derived Cells
Markedly Improved0
Moderately improved3
Slightly improved9
No change5
Slightly worse0
Moderately worse0
Markedly worse0
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Improvement in Underactive Bladder Symptoms at 12 Months.
ParticipantsAutologous Muscle Derived Cells
Very much better0
Much better3
A little bit better9
No change5
A little worse0
Much worse0
Very much worse0
SecondaryChange 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
Reported as:
Mean · units on a scale
Change in Incontinence Questionnaire (ICIQ) Long Form Score From Baseline at 12 Months.
units on a scaleAutologous Muscle Derived Cells
Female (ICIQ-FLUTS) long form0.6667 ± 5.1
Male (ICIQ-MLUTS) long form1.071 ± 9.600
SecondaryChange 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
Reported as:
Mean · score on a scale
Change in Underactive Bladder Questionnaire (UABQ) Score From Baseline at 12 Months
score on a scaleAutologous Muscle Derived Cells
Change in Underactive Bladder Questionnaire (UABQ) Score From Baseline at 12 Months5.7 ± 2.7
SecondaryThe 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
Reported as:
Mean · number of voids/day
The Change in Number of Independent Voiding Occurrences Per Day on the 3-day Bladder Diary From Baseline at 12 Months.
number of voids/dayAutologous 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 ± 5.3
SecondaryThe 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
Reported as:
Mean · number of voids/day
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.
number of voids/dayAutologous 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 ± 1.6
SecondaryThe 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
Reported as:
Mean · milliliters/day
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.
milliliters/dayAutologous 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 ± 1100.0
SecondaryThe 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
Reported as:
Mean · milliliters/day
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.
milliliters/dayAutologous 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 ± 2100
SecondaryThe 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
Reported as:
Mean · bladder leaks per day
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.
bladder leaks per dayAutologous 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 ± 0

Adverse events

Collected over 18 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Autologous Muscle Derived Cells0/20 (0%)4/20 (20%)20/20 (100%)
Most frequent serious events
Most frequent serious events
EventAutologous Muscle Derived Cells
Aortic stenosisCardiac disorders1/20
Closed fracture of tibiaMusculoskeletal and connective tissue disorders1/20
PyelonephritisRenal and urinary disorders1/20
Fracture of HumerusMusculoskeletal and connective tissue disorders1/20
Fracture of femoral neckMusculoskeletal and connective tissue disorders1/20
Most frequent other events
Most frequent other events
EventAutologous Muscle Derived Cells
Urinary tract infectionRenal and urinary disorders10/20
InfluenzaRespiratory, thoracic and mediastinal disorders3/20
PainGeneral disorders3/20
BruiseSkin and subcutaneous tissue disorders2/20
FallGeneral disorders2/20
FatigueGeneral disorders2/20

Baseline characteristics

Of initial 23 subjects consented, 3 subjects withdrew from study prior to collection of initial data. Demographic data is not available for these 3 subjects.

Age, Continuous
Age, Continuous(years)Autologous Muscle Derived Cells
Mean61.45 ± 12.00
Sex: Female, Male
Sex: Female, Male(Participants)Autologous Muscle Derived Cells
Female4
Male16
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Autologous Muscle Derived Cells
Hispanic or Latino0
Not Hispanic or Latino20
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Autologous Muscle Derived Cells
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White20
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Autologous Muscle Derived Cells
United States20
07

Study locations

1 site
  • Beaumont Health
    Royal Oak, Michigan 48073, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Apr 18, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT02463448
Lead sponsor
Jason Gilleran
Responsible party
Jason Gilleran (Principal Investigator, William Beaumont Hospitals) — Sponsor-investigator
First posted
Jun 4, 2015
Start date
Nov 16, 2016
Primary completion
Dec 2019
Completion
Nov 2020
Results posted
Jan 19, 2022
Last update
Jan 19, 2022

Study contacts

Jason Gilleran, MD
principal investigator · Beaumont Health

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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