Autologous Muscle Derived Cells for Underactive Bladder

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.

Study Overview

• Status: Completed
• Conditions: Urinary Incontinence; Urinary Retention
• Intervention / Treatment: Biological: Autologous Muscle Derived Cells

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jason Gilleran
• Investigators: Principal Investigator: Jason Gilleran, MD, Beaumont Health

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: May 27, 2015
• First Submitted That Met QC Criteria: June 3, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Underactive Bladder
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Urinary Incontinence; Urinary Retention; Urinary Bladder, Underactive
• Other Study ID Numbers: 2015-134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO