Autologous Cell Therapy for Stress Urinary Incontinence in Males Following Prostate Surgery

• Sponsor: Cook MyoSite (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02291432
• Collaborator: (none)
• Enrollment: 25
• Locations: 5
• Arm: 1
• Actual Duration (Months): 52.2
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To study the safety and potential efficacy of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) for the treatment of male stress urinary incontinence (SUI) for patients that have undergone prior prostate surgery.

Condition or Disease	Intervention/Treatment	Phase
Urinary Incontinence; Stress; Urination Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations	Biological: autologous muscle-derived cells (AMDC)	Phase 1/Phase 2

Detailed Description

This preliminary, prospective, single-arm clinical study will evaluate the safety and potential efficacy of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) for the treatment of male stress urinary incontinence (SUI) that develops following prostate surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Muscle Cell Mediated Therapy for Stress Urinary Incontinence in Males Following Prostate Surgery: An Investigation of Cook MyoSite Autologous Muscle Derived Cells
• Actual Study Start Date: Feb 19, 2015
• Actual Primary Completion Date: Jun 28, 2019
• Actual Study Completion Date: Jun 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMDC-USR Cell treatment	Biological: autologous muscle-derived cells (AMDC); Cell treatment

Outcome Measures

Primary Outcome Measures

1. Rate of Product-related, Biopsy Procedure-related, and Injection Procedure-related Adverse Events [24 months]

   Safety of AMDC-USR following treatment of SUI in male patients who have undergone prior prostate surgery was determined by the frequency and severity of adverse events related to study procedures and study product through 24 months following treatment of SUI in male patients who have undergone prior prostate surgery.

2. Volume of Post-void Residual (PVR) Urine [1, 3, 6, and 12 months]

   Post void residual volume (PVR) was assessed through 12 months post-treatment to monitor potential retention or obstruction.

Secondary Outcome Measures

1. Change From Baseline in Amount of Urine Leakage (Median 24 Hour Pad Weight) [1, 3, 6, and 12 months]

   Change in the amount of urine leakage from baseline was assessed by 24-hour pad test at 1, 3, 6, and 12 months post-treatment. Amount of urine leakage experienced by subject at home during a 24-hour period; all pads used during test period are weighed before and after use and differences in weights represent the amount of urine leaked.

2. Number of Participants With a Change From Baseline in Amount of Urine Leakage (Categorial ≥50% Reduction in 24-hour Pad Weight) [1, 3, 6, and 12 months]

   Change in the amount of urine leakage from baseline was assessed by a 24-hour pad test at 1, 3, 6, and 12 months post-treatment. Amount of urine leakage experienced by subject at home during a 24-hour period; all pads used during test period are weighed before and after use and differences in weights represent the amount of urine leaked.

3. Median Change From Baseline in Patient-reported Quality of Life (QOL) - Incontinence Quality of Life (I-QOL) Questionnaire [1, 3, 6, and 12 months]

   Median change from baseline in patient-reported quality of life (QOL) was assessed by the Incontinence Quality of Life (I-QOL) questionnaire at 1, 3, 6 and 12 months post-treatment. The I-QOL questionnaire was a validated, 22-item tool used to assess QOL of participants with urinary incontinence. Scored 0 to100, with higher scores indicating a better QOL.

4. Median Change From Baseline in Patient-reported Symptom Severity- International Consultation on Incontinence Questionnaire (ICIQ) [Baseline, 1, 3, 6, and 12 months]

   Median change from baseline in patient-reported symptom severity was assessed by the International Consultation on Incontinence Questionnaire (ICIQ) questionnaire at 1, 3, 6, and 12 months post-treatment. The ICIQ questionnaire was a validated 4-item tool used to assess symptom severity of participants with urinary incontinence. Scored 0 to 21, with lower scores indicating a better symptom severity.

5. Median Change in Patient-reported Incontinence Symptom Severity - International Prostate Symptom Score (I-PSS) Questionnaire [Baseline, 1, 3, 6, and 12 months]

   Patient-reported incontinence symptom severity was assessed by questionnaires at 1, 3, 6, and 12 months post-treatment using the International Prostate Symptom Score (I-PSS) questionnaire. The I-PSS was a validated questionnaire used to assess the severity of three urine storage symptoms (frequency, nocturia, urgency), four voiding symptoms (feeling of incomplete emptying, intermittency, straining, and a weak stream) and the degree of bother associated with those symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms, and 20 to 35 indicates severe symptoms.

6. Distribution of Patient-reported Incontinence Symptom Severity Scores - Patient Global Impression of Severity (PGI-S) Questionnaire [1, 3, 6, and 12 months]

   Patient-reported incontinence symptom severity was assessed by questionnaires at 1, 3, 6, and 12 months post-treatment using the Patient Global Impression of Severity (PGI-S) questionnaire. The PGI-S was a global assessment of symptom severity compared with severity before treatment started. Ratings that could be selected were: 1-normal, 2-mild, 3-moderate, and 4-severe. Percentages of participants in each category were determined at each visit.

7. Distribution of Patient-reported Incontinence Symptom Severity Scores - Patient Global Impression of Improvement (PGI-I) Questionnaire [1, 3, 6, and 12 months]

   Patient-reported incontinence symptom severity was assessed by questionnaires at 1, 3, 6, and 12 months post-treatment using the Patient Global Impression of Improvement (PGI-I) questionnaire. The PGI-I was a global assessment of symptom severity in which participants selected the following ratings: 1-Very much better, 2-Much better, 3-A little better, 4-No change, 5-A little worse, 6-Much worse, and 7-Very much worse. Percentages of participants in each category were determined at each visit.

8. Median Change From Baseline in Patient-reported Erectile Dysfunction (ED) - Index of Erectile Function (IIEF-5) Questionnaire [Baseline, 1, 3, 6, and 12 months]

   SUI and ED can be comorbidities that develop following prostate surgery; median change from baseline in patient-reported Erectile Dysfunction (ED) was assessed by the 5-Item International Index of Erectile Function (IIEF-5). The IIEF-5 questionnaire was a validated 5-item tool used to assess to presence and severity of erectile dysfunction. Scored from 5 to 25, with lower scores indicating less ED symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male, at least 18 years old, with primary symptoms of SUI following prostate surgery,

• Patient has undergone prostate surgery but has not undergone radiation therapy, cryotherapy, or high-intensity focused ultrasound of the prostate,

• SUI severity should be ≥10 g and <400 g of urine leakage over 24 hours,

• Patient has failed to achieve acceptable resolution of SUI symptoms following prior therapy.

Exclusion Criteria:

• Symptoms of only urge urinary incontinence,

• Symptoms of stress urinary incontinence prior to prostate surgery,

• Routinely has more than 2 episodes of awakening to void during normal sleeping hours,

• Compromised immune system due to disease state, chronic corticosteroid use, or other immunosuppressive therapy,

• Previously treated with a periurethral balloon or adjustable sling for urinary incontinence,

• Symptoms of overflow incontinence

• Additional medical restrictions as specified in the Clinical Investigation Plan,

• Additional anatomical restrictions as specified in the Clinical Investigation Plan.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami School of Medicine	Miami	Florida	United States	33136
2	Emory University Hospital	Atlanta	Georgia	United States	30322
3	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
4	McKay Urology	Charlotte	North Carolina	United States	28207
5	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Cook MyoSite

Investigators

• Principal Investigator: Kenneth Peters, MD, Beaumont Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 17, 2015

More Information

Publications

None provided.

• Responsible Party: Cook MyoSite
• ClinicalTrials.gov Identifier: NCT02291432
• Other Study ID Numbers: 13-11
• First Posted: Nov 14, 2014
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cook MyoSite: Urinary Incontinence, Stress; Tissue Therapy (Cell Therapy)
• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Urinary Incontinence, Stress; Urologic Diseases; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations

Study Results

Participant Flow

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Period Title: Overall Study
STARTED	25
Muscle Biopsy	25
AMDC Injection	23
1-Month Follow Up	23
3-Month Follow Up	23
6-Month Follow Up	23
12-Month Follow Up	23
COMPLETED	23
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 autologous muscle-derived cells (AMDCs).
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 32%
>=65 years	17 68%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Age, Customized (years) [Mean (Standard Deviation) ]
Participant Age	67.2 (5.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	25 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4%
White	24 96%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	25 100%
Urinary Incontinence Type (Count of Participants)
Pure Stress Urinary Incontinence	4 16%
Mixed Urinary Incontinence, Stress Predominant	17 68%
Mixed Urinary Incontinence, Urge Predominant	4 16%
24-hour Pad Test Weight (grams) [Median (Full Range) ]
Median (Full Range) [grams]	109.1
Incontinence Quality of Life (I-QOL) (scores on scales) [Median (Full Range) ]
Median (Full Range) [scores on scales]	59.1
International Consultation on Incontinence Questionnaire (ICIQ) (scores on scales) [Median (Full Range) ]
Median (Full Range) [scores on scales]	13
International Prostate Symptom Score (IPSS) (scores on scales) [Median (Full Range) ]
Median (Full Range) [scores on scales]	9
International Index of Erectile Function (IIEF) (scores on scales) [Median (Full Range) ]
Median (Full Range) [scores on scales]	13
Patient Global Impression of Severity (PGI-S) Questionnaire (Count of Participants)
Normal	0 0%
Mild	8 32%
Moderate	13 52%
Severe	4 16%

Outcome Measures

1. Primary Outcome

Title	Rate of Product-related, Biopsy Procedure-related, and Injection Procedure-related Adverse Events
Description	Safety of AMDC-USR following treatment of SUI in male patients who have undergone prior prostate surgery was determined by the frequency and severity of adverse events related to study procedures and study product through 24 months following treatment of SUI in male patients who have undergone prior prostate surgery.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All subjects enrolled (biopsied)

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	25
Study product-related serious adverse events	0
Study Product-related adverse events	2
Injection procedure-related adverse events	0
Biopsy procedure-related adverse events	12

2. Primary Outcome

Title	Volume of Post-void Residual (PVR) Urine
Description	Post void residual volume (PVR) was assessed through 12 months post-treatment to monitor potential retention or obstruction.
Time Frame	1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Post void residual volume 1 month	0
Post void residual volume 3 months	0
Post void residual volume 6 months	0
Post void residual volume 12 months	0

3. Secondary Outcome

Title	Change From Baseline in Amount of Urine Leakage (Median 24 Hour Pad Weight)
Description	Change in the amount of urine leakage from baseline was assessed by 24-hour pad test at 1, 3, 6, and 12 months post-treatment. Amount of urine leakage experienced by subject at home during a 24-hour period; all pads used during test period are weighed before and after use and differences in weights represent the amount of urine leaked.
Time Frame	1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
24 hour pad weight at 1 month	101.2
24 hour pad weight at 3 months	59.5
24 hour pad weight at 6 months	104.9
24 hour pad weight at 12 months	85.7

4. Secondary Outcome

Title	Number of Participants With a Change From Baseline in Amount of Urine Leakage (Categorial ≥50% Reduction in 24-hour Pad Weight)
Description	Change in the amount of urine leakage from baseline was assessed by a 24-hour pad test at 1, 3, 6, and 12 months post-treatment. Amount of urine leakage experienced by subject at home during a 24-hour period; all pads used during test period are weighed before and after use and differences in weights represent the amount of urine leaked.
Time Frame	1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
≥50% reduction in 24 hour pad weight at 1 month	2 8%
≥50% reduction in 24 hour pad weight at 3 months	4 16%
≥50% reduction in 24 hour pad weight at 6 months	4 16%
≥50% reduction in 24 hour pad weight at 12 months	7 28%

5. Secondary Outcome

Title	Median Change From Baseline in Patient-reported Quality of Life (QOL) - Incontinence Quality of Life (I-QOL) Questionnaire
Description	Median change from baseline in patient-reported quality of life (QOL) was assessed by the Incontinence Quality of Life (I-QOL) questionnaire at 1, 3, 6 and 12 months post-treatment. The I-QOL questionnaire was a validated, 22-item tool used to assess QOL of participants with urinary incontinence. Scored 0 to100, with higher scores indicating a better QOL.
Time Frame	1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Change in I-QOL total score at 1 month	-6.8
Change in I-QOL total score at 3 months	0
Change in I-QOL total score at 6 months	-9.1
Change in I-QOL total score at 12 months	-9.1

6. Secondary Outcome

Title	Median Change From Baseline in Patient-reported Symptom Severity- International Consultation on Incontinence Questionnaire (ICIQ)
Description	Median change from baseline in patient-reported symptom severity was assessed by the International Consultation on Incontinence Questionnaire (ICIQ) questionnaire at 1, 3, 6, and 12 months post-treatment. The ICIQ questionnaire was a validated 4-item tool used to assess symptom severity of participants with urinary incontinence. Scored 0 to 21, with lower scores indicating a better symptom severity.
Time Frame	Baseline, 1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Change in ICIQ score at 1 month	0
Change in ICIQ score at 3 months	0
Change in ICIQ score at 6 months	0
Change in ICIQ score at 12 months	1

7. Secondary Outcome

Title	Median Change in Patient-reported Incontinence Symptom Severity - International Prostate Symptom Score (I-PSS) Questionnaire
Description	Patient-reported incontinence symptom severity was assessed by questionnaires at 1, 3, 6, and 12 months post-treatment using the International Prostate Symptom Score (I-PSS) questionnaire. The I-PSS was a validated questionnaire used to assess the severity of three urine storage symptoms (frequency, nocturia, urgency), four voiding symptoms (feeling of incomplete emptying, intermittency, straining, and a weak stream) and the degree of bother associated with those symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms, and 20 to 35 indicates severe symptoms.
Time Frame	Baseline, 1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Change in I-PSS score at 1 month	1
Change in I-PSS score at 3 months	1
Change in I-PSS score at 6 months	1
Change in I-PSS score at 12 months	1

8. Secondary Outcome

Title	Distribution of Patient-reported Incontinence Symptom Severity Scores - Patient Global Impression of Severity (PGI-S) Questionnaire
Description	Patient-reported incontinence symptom severity was assessed by questionnaires at 1, 3, 6, and 12 months post-treatment using the Patient Global Impression of Severity (PGI-S) questionnaire. The PGI-S was a global assessment of symptom severity compared with severity before treatment started. Ratings that could be selected were: 1-normal, 2-mild, 3-moderate, and 4-severe. Percentages of participants in each category were determined at each visit.
Time Frame	1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Normal	1 4%
Mild	3 12%
Moderate	13 52%
Severe	6 24%
Normal	0 0%
Mild	8 32%
Moderate	12 48%
Severe	3 12%
Normal	0 0%
Mild	9 36%
Moderate	11 44%
Severe	3 12%
Normal	1 4%
Mild	6 24%
Moderate	13 52%
Severe	3 12%

9. Secondary Outcome

Title	Distribution of Patient-reported Incontinence Symptom Severity Scores - Patient Global Impression of Improvement (PGI-I) Questionnaire
Description	Patient-reported incontinence symptom severity was assessed by questionnaires at 1, 3, 6, and 12 months post-treatment using the Patient Global Impression of Improvement (PGI-I) questionnaire. The PGI-I was a global assessment of symptom severity in which participants selected the following ratings: 1-Very much better, 2-Much better, 3-A little better, 4-No change, 5-A little worse, 6-Much worse, and 7-Very much worse. Percentages of participants in each category were determined at each visit.
Time Frame	1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Very much better	1 4%
Much better	0 0%
A little better	4 16%
No change	18 72%
A little worse	0 0%
Very much better	0 0%
Much better	1 4%
A little better	12 48%
No change	9 36%
A little worse	1 4%
Very much better	0 0%
Much better	3 12%
A little better	11 44%
No change	7 28%
A little worse	2 8%
Very much better	0 0%
Much better	4 16%
A little better	11 44%
No change	5 20%
A little worse	3 12%

10. Secondary Outcome

Title	Median Change From Baseline in Patient-reported Erectile Dysfunction (ED) - Index of Erectile Function (IIEF-5) Questionnaire
Description	SUI and ED can be comorbidities that develop following prostate surgery; median change from baseline in patient-reported Erectile Dysfunction (ED) was assessed by the 5-Item International Index of Erectile Function (IIEF-5). The IIEF-5 questionnaire was a validated 5-item tool used to assess to presence and severity of erectile dysfunction. Scored from 5 to 25, with lower scores indicating less ED symptoms.
Time Frame	Baseline, 1, 3, 6, and 12 months

Outcome Measure Data

Analysis Population Description

All subjects injected

Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
Measure Participants	23
Change in IEEF-5 score at 1 month	0
Change in IEEF-5 score at 3 months	0
Change in IEEF-5 score at 6 months	0
Change in IEEF-5 score at 12 months	0

Adverse Events

Time Frame	Adverse events were monitored from enrollment through study exit - 24 months total.
Adverse Event Reporting Description	All adverse events were collected at baseline, 1 month, 3 months, 6 months, 12 months, and 24 months post-treatment. Any adverse events occurring in ≥ 5% of participants are reported. Adverse events assessed as AMDC product-related or biopsy procedure-related were reported regardless of frequency threshold. No injection procedure-related adverse events were reported.
Arm/Group Title	AMDC-USR
Arm/Group Description	Single intraurethral injection of 150 x 10^6 Autologous Muscle-Derived Cells (AMDCs)
All Cause Mortality
	AMDC-USR
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Serious Adverse Events
	AMDC-USR
	Affected / at Risk (%)	# Events
Total	4/25 (16%)
Cardiac disorders
Myocardial infarction	1/25 (4%)	1
Infections and infestations
Pneumonia	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Spinal column stenosis	1/25 (4%)	1
Spondylolisthesis	1/25 (4%)	1
Nervous system disorders
Cerebrovascular accident	1/25 (4%)	1
Renal and urinary disorders
Nephrolithiasis	1/25 (4%)	2
Other (Not Including Serious) Adverse Events
	AMDC-USR
	Affected / at Risk (%)	# Events
Total	9/25 (36%)
Gastrointestinal disorders
Abdominal Pain	2/25 (8%)	2
Infections and infestations
Sinusitis	2/25 (8%)	7
Laceration	2/25 (8%)	2
Injury, poisoning and procedural complications
Post procedural contusion	2/25 (8%)	2
Post procedural swelling	1/25 (4%)	1
Procedural hypotension	1/25 (4%)	1
Procedural nausea	1/25 (4%)	1
Procedural pain	3/25 (12%)	3
Fall	2/25 (8%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/25 (8%)	2
Nervous system disorders
Hypoaesthesia	1/25 (4%)	1
Renal and urinary disorders
Micturition urgency	1/25 (4%)	1
Pollakiuria	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Erythema	1/25 (4%)	1
Hyperhidrosis	1/25 (4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.