An Investigation of the Safety of 4 Different Doses of Autologous Muscle Derived Cells as Therapy for Stress Urinary Incontinence

• Sponsor: Cook MyoSite (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00847535
• Collaborator: (none)
• Enrollment: 66
• Locations: 3
• Arms: 2
• Actual Duration (Months): 36.8
• Patients Per Site: 22
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is a clinical investigation approved by US FDA and Canadian Health Authority to study the safety and potential effectiveness of the autologous muscle cells for the treatment of stress urinary incontinence.

Condition or Disease	Intervention/Treatment	Phase
Stress Urinary Incontinence; Cell Therapy	Biological: autologous muscle cell injection	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Muscle Cell Mediated Therapy for Stress Urinary Incontinence: An Investigation of the Safety of 4 Different Doses of Autologous Muscle Derived Cells.
• Actual Study Start Date: Oct 9, 2008
• Actual Primary Completion Date: Nov 2, 2011
• Actual Study Completion Date: Nov 2, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 Transurethral dose escalation	Biological: autologous muscle cell injection; Injection of autologous muscle cells
Other: 2 Periurethral dose escalation	Biological: autologous muscle cell injection; Injection of autologous muscle cells

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Experienced Biopsy Procedure-related Adverse Events [at biopsy or between biopsy and treatment]

   Biopsy was required to generate AMDC products. Biopsy procedure-related events were defined as systemic responses to the biopsy procedure or injury at the biopsy site. Since biopsy occurred prior to AMDC treatment, results are presented independent of AMDC dose received. All biopsy procedure-related events either self-resolved or were easily treated.

2. Biopsy Procedure-related Adverse Events [at biopsy or between biopsy and treatment]

   Biopsy was required to generate AMDC products. Biopsy procedure-related events were defined as systemic responses to the biopsy procedure or injury at the biopsy site. Since biopsy occurred prior to AMDC treatment, results are presented independent of AMDC dose received. All biopsy procedure-related events either self-resolved or were easily treated.

3. Number of Participants That Experienced Injection Procedure-related Adverse Events [30 days]

   AMDC treatment was administered via intrasphincteric injection. Injection procedure-related events were defined as systemic responses to the injection procedure or genitourinary events occurring within 30 days of the injection procedure that could be attributed to cystoscopy or catheterization. Since these events could be attributed to the injection procedure, results are considered independent of AMDC dose received. All injection procedure-related events self-resolved or were easily treated.

4. Injection Procedure-related Adverse Events [30 days]

   AMDC treatment was administered via intrasphincteric injection. Injection procedure-related events were defined as systemic responses to the injection procedure or genitourinary events occurring within 30 days of the injection procedure that could be attributed to cystoscopy or catheterization. Since these events could be attributed to the injection procedure, results are considered independent of AMDC dose received. All injection procedure-related events self-resolved or were easily treated.

5. Number of Participants That Experienced AMDC Product-related Adverse Events [12 months]

   If an immune response after injection or any urinary retention occurred and seemed suspicious, the physicians were consulted to determine whether the effect was likely related to the AMDC product. No adverse events reported during the study were adjudicated as AMDC product-related.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient has SUI with normal detrusor activity confirmed with urodynamics

• Patient has bladder capacity >200 mL

• Patient's incontinence has not shown any improvement for at least -6 months

• Patient has failed prior treatments (e.g., behavior modification, bladder exercises, biofeedback, electrical stimulation, bulking injections, urethral suspensions and/or drug therapy)

Exclusion Criteria:

• Patient has known vesicoureteral reflux, vaginal prolapse beyond the introitus, or other significant pelvic floor abnormalities with high pressure instability

• Patient has a neuromuscular disorder (e.g., muscular dystrophy, multiple sclerosis)

• Patient has uncontrolled diabetes

• Patient is pregnant, lactating, or plans to become pregnant during the course of the study

• Patient is morbidly obese (defined as 100 pounds over their ideal body weight, or BMI ≥40) and would not be expected to benefit from treatment

• Patient has current or acute conditions involving cystitis or urethritis

• Patient is scheduled to receive radiation treatment to the vicinity

• Patients with a history of radiation treatment to the urethra or adjacent structures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wm Beaumont Hospital	Royal Oak	Michigan	United States	48073
2	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
3	Sunnybrook Health Sciences Center	Toronto	Ontario	Canada	M4N 3M5

Sponsors and Collaborators

• Cook MyoSite

Investigators

• Principal Investigator: Kenneth Peters, MD, William Beaumont Hospitals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Autologous muscle derived cells for treatment of stress urinary incontinence in women

Publications

None provided.

• Responsible Party: Cook MyoSite
• ClinicalTrials.gov Identifier: NCT00847535
• Other Study ID Numbers: 08-006; IND1
• First Posted: Feb 19, 2009
• Last Update Posted: Jul 1, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Urinary Incontinence, Stress

Study Results

Participant Flow

Pre-assignment Detail	66 participants were biopsied, 64 participants received injections.

Arm/Group Title	Part I: Transurethral Injection	Part I: Periurethral Injection	Part II: Transurethral Injection
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women. Following skeletal muscle biopsy of the thigh to obtain starting material for production of AMDC, patients underwent intrasphincteric injection of AMDC.	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women. Following skeletal muscle biopsy of the thigh to obtain starting material for production of AMDC, patients underwent intrasphincteric injection of AMDC.	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women. Following skeletal muscle biopsy of the thigh to obtain starting material for production of AMDC, patients underwent intrasphincteric injection of AMDC.
Period Title: Overall Study
STARTED	24	24	16
10 Million AMDC	8	8	0
50 Million AMDC	8	8	0
100 Million AMDC	8	8	8
200 Million AMDC	0	0	8
COMPLETED	22	22	15
NOT COMPLETED	2	2	1

Baseline Characteristics

Arm/Group Title	Patients Treated With AMDC
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women.
Overall Participants	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (1)
Sex: Female, Male (Count of Participants)
Female	64 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Experienced Biopsy Procedure-related Adverse Events
Description	Biopsy was required to generate AMDC products. Biopsy procedure-related events were defined as systemic responses to the biopsy procedure or injury at the biopsy site. Since biopsy occurred prior to AMDC treatment, results are presented independent of AMDC dose received. All biopsy procedure-related events either self-resolved or were easily treated.
Time Frame	at biopsy or between biopsy and treatment

Outcome Measure Data

Analysis Population Description

During the study, 66 patients underwent a total of 78 biopsies.

Arm/Group Title	Patients With Biopsy
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women.
Measure Participants	66
Number [participants]	3 4.7%

2. Primary Outcome

Title	Biopsy Procedure-related Adverse Events
Description	Biopsy was required to generate AMDC products. Biopsy procedure-related events were defined as systemic responses to the biopsy procedure or injury at the biopsy site. Since biopsy occurred prior to AMDC treatment, results are presented independent of AMDC dose received. All biopsy procedure-related events either self-resolved or were easily treated.
Time Frame	at biopsy or between biopsy and treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Biopsy
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women.
Measure Participants	66
Wound hematoma	2
Post procedural hemorrhage	1
Joint swelling	1
Feeling hot	1
Procedural dizziness	1
Hyperhidrosis	1

3. Primary Outcome

Title	Number of Participants That Experienced Injection Procedure-related Adverse Events
Description	AMDC treatment was administered via intrasphincteric injection. Injection procedure-related events were defined as systemic responses to the injection procedure or genitourinary events occurring within 30 days of the injection procedure that could be attributed to cystoscopy or catheterization. Since these events could be attributed to the injection procedure, results are considered independent of AMDC dose received. All injection procedure-related events self-resolved or were easily treated.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Sixty-four patients underwent intrasphincteric injection of AMDC.

Arm/Group Title	Patients Treated With AMDC
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women.
Measure Participants	64
Number [participants]	8 12.5%

4. Primary Outcome

Title	Injection Procedure-related Adverse Events
Description	AMDC treatment was administered via intrasphincteric injection. Injection procedure-related events were defined as systemic responses to the injection procedure or genitourinary events occurring within 30 days of the injection procedure that could be attributed to cystoscopy or catheterization. Since these events could be attributed to the injection procedure, results are considered independent of AMDC dose received. All injection procedure-related events self-resolved or were easily treated.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Treated With AMDC
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women.
Measure Participants	64
Dysuria	3
Vulvovaginal pruritis	3
Pelvic/abdominal pain	2
Hematuria	2
Vulvovaginal burning sensation	1
Sensation of foreign body	1
Pollakiuria	1
Micturition urgency	1

5. Primary Outcome

Title	Number of Participants That Experienced AMDC Product-related Adverse Events
Description	If an immune response after injection or any urinary retention occurred and seemed suspicious, the physicians were consulted to determine whether the effect was likely related to the AMDC product. No adverse events reported during the study were adjudicated as AMDC product-related.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Treated With AMDC
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women.
Measure Participants	64
Number [participants]	0 0%

Adverse Events

Time Frame	Biopsy to treatment, 12 months Post-treatment
Adverse Event Reporting Description	During the study, 66 patients underwent a total of 78 biopsies, and 64 patients underwent intrasphincteric injection of AMDC.
Arm/Group Title	Patients
Arm/Group Description	Autologous Muscle-Derived Cells (AMDC) are intended for use in the treatment of stress urinary incontinence (SUI) in women
All Cause Mortality
	Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients
	Affected / at Risk (%)	# Events
Total	8/66 (12.1%)
Cardiac disorders
Post-treatment: Angina unstable	1/64 (1.6%)	1
Post-treatment: Cardiac failure congestive	1/64 (1.6%)	1
Post-treatment: Myocardial infarction	1/64 (1.6%)	1
Gastrointestinal disorders
Post-treatment: Enterocolitis infectious	1/64 (1.6%)	1
Post-treatment: Small intestinal obstruction	1/64 (1.6%)	1
Immune system disorders
Biopsy to treatment: Drug hypersensitiviy	1/66 (1.5%)	1
Musculoskeletal and connective tissue disorders
Biopsy to treatment: Femoral neck fracture	1/66 (1.5%)	1
Post-treatment: Intervertebral disc protrusion	1/64 (1.6%)	1
Surgical and medical procedures
Post-treatment: Intervertebral disc operation	1/64 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Patients
	Affected / at Risk (%)	# Events
Total	18/66 (27.3%)
Renal and urinary disorders
Biopsy to treatment: Urinary tract infection	4/66 (6.1%)	4
Post-treatment: Dysuria	5/64 (7.8%)	5
Post-treatment: Pollakiuria	4/64 (6.3%)	4
Post-treatment: Urinary tract infection	5/64 (7.8%)	9
Respiratory, thoracic and mediastinal disorders
Post-treatment: Bronchitis	4/64 (6.3%)	4

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.