Safety and Efficacy Study of Intrasphincteric Autologous Myoblast Injection to Treat Stress Urinary Incontinence

This study has been completed.
Sponsor:
Collaborator:
Innovacell Biotechnologie AG
Information provided by:
University Medical Centre Ljubljana
ClinicalTrials.gov Identifier:
NCT01355133
First received: May 12, 2011
Last updated: May 16, 2011
Last verified: May 2011
  Purpose

The purpose of this pilot clinical study is to determine if intrasphincteric autologous myoblast injections in combination with electrical stimulation are safe and effective in treating stress urinary incontinence, confirming the optimal dose and assessing tolerability of the procedure.


Condition Intervention Phase
Stress Urinary Incontinence
Biological: Transurethral intrasphincteric autologous myoblast implantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transurethral Ultrasound-directed Injection of Autologous Myoblasts in Combination With Functional Electrical Stimulation in Patients With Intrinsic Urinary Sphincter Deficiency

Resource links provided by NLM:


Further study details as provided by University Medical Centre Ljubljana:

Primary Outcome Measures:
  • Change from baseline in Incontinence episode frequency (IEF) [ Time Frame: 6 months post-implantation ] [ Designated as safety issue: No ]
    The median percent change from baseline in IEF using the 3-day bladder diary analysis

  • Change from baseline in Quality of Life (I-QOL) total score [ Time Frame: 6 months post-implantation ] [ Designated as safety issue: No ]
    Mean improvement from baseline for the Incontinence Quality of Life (I-QOL) total score

  • Change from baseline in the Incontinence score [ Time Frame: 6 months post-implantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to onset of response [ Time Frame: Up to 6 months post-implantation (based on recordings at baseline, at implantation, at 6 weeks, 3 months and 6 months post-impalntation) ] [ Designated as safety issue: No ]
    Time to onset of response; time to maximum response; maintenance of response observed through changes in Incontinence episode frequency(IEF), Visual analog scale of the degree of suffering (VAS), Modified patient global impression of improvement(PGI-I*), fixed bladder stress test and I-QOL.

  • Change from baseline in Fixed bladder stress test outcome [ Time Frame: Baseline, 6 months postimplantation. ] [ Designated as safety issue: No ]
  • Rate for subsequent incontinence surgery [ Time Frame: 6 months post-implantation ] [ Designated as safety issue: No ]
  • Change from baseline in Urodynamic evaluation [ Time Frame: 6 months post-implantation ] [ Designated as safety issue: No ]
    Cystometry, urethral pressure profile (UPP), 1-hour pad-test.

  • Safety [ Time Frame: Up to 6 months post-implantation ] [ Designated as safety issue: Yes ]

    Number of adverse events, patholgical lab values, vital signs and weight recordings. Number of immediate and delayed complications of cell injection, including surgical injury, scars, urinary tract infection, inflammation, pelvic pain, prolonged urinary retention, voiding dysfunction, de novo urge incontinence, hematuria, hyperplasia or tumours.

    Any clinically significant findings based on physical examination, standard haematology, clinical chemistry and urinalysis profiles, Electrocardiogram (ECG), Blood Pressure (BP), pulse rate and adverse events recordings.


  • Change from baseline in Urinary incontinence semiquantitative (UIS) [ Time Frame: 6 months post-implantation ] [ Designated as safety issue: No ]
    Amount of leaked urine measured semiqantitative from a 3-day bladder diary.


Enrollment: 40
Study Start Date: August 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Transurethral intrasphincteric autologous myoblast implantation
    Patients undergo upper arm muscle biopsy to isolate and cultivate autologous myoblasts. Using the ultrasound-directed transurethral medical device, 15-18 aliquots (50 - 100 µl per depot) of the 2 ml myoblasts/media suspension are directly injected into the urethral rhabdosphincter at two different levels. The procedure is a single-dose injection of a cell count in range of 1x106 -5x107 cells, depending of the size/quality of the biopsy and quality of outgrowing cells in order to identify possible dose related effects. To possibly enhance cell integration following implantation, a course of transvaginal electrical stimulation is undertaken.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female outpatients, predominant clinical diagnosis of SUI
  • Have discrete episodes of incontinence (that is, are dry between episodes and not continuously leaking urine, synchronous with increased intra-abdominal pressure from coughing, sneezing, exercising, etc.)
  • Have a positive Fixed Bladder Volume Cough Stress Test (CST) result; and post void residual volume of <50 ml
  • Report normal urinary diurnal (≤8/day) and nocturnal (≤2/night) frequency per micturition history
  • Have had symptoms of SUI for a minimum of 3 months prior to study entry
  • Can independently use toilet without difficulty
  • If patients regularly use laxatives, stool softeners, or stool-bulking agents (for example, fibre supplements), the use of these products should remain constant during participation in the study.
  • Competent to comprehend, sign, and date an Ethics Committee approved informed consent form before any study-specific procedure is performed.
  • Are women of non-childbearing potential by reason of hysterectomy, other surgery, or natural menopause, or are women of childbearing potential who test negative for pregnancy at the time of enrolment based on a urine pregnancy test and agree to use a medically accepted means of contraception (for example, intrauterine device [IUD], oral or injectable contraceptives, implant, barrier device, sterilization, abstinence, or sex with a vasectomized male partner) for the duration of the study. Women using oral contraceptives or hormone replacement therapy must have a stable dose and regimen for greater than or equal to 3 months prior to entry into the study.

Exclusion Criteria:

  • Previous diagnosis of any of the following conditions, disorders, or diseases of the urinary tract:

    • Greater than Stage I Anterior (cystocoele), Apical (uteri), or Posterior (rectocoele) Compartment Prolepses as per the POP-Q)
    • Ureteric bladder, urethral or rectal fistula
    • Uncorrected congenital abnormality leading to urinary incontinence
    • Interstitial cystitis
    • Urinary urgency that results in leakage (as a predominant symptom)
    • Adult enuresis
    • Urodynamically proven:
  • detrusor instability
  • sensory urgency defined as first sensation of bladder fill (urge to void) of <100 ml; bladder capacity of <300 ml
  • voiding difficulty
  • Have no sensation at any time during the simple filling cystometry procedure
  • Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before enrollment
  • Have a symptomatic urinary tract infection (UTI); or have a history of four or more urinary tract infections in the preceding year.
  • Have prolonged menstruation (>14 days per month).
  • Have history of (or currently have) urogenital cancer.
  • Suffer from severe constipation defined as less than one bowel movement per week
  • Are pregnant, <12 months postpartum or are lactating
  • Have had any major inpatient surgery within 3 months prior to study entry
  • Known infection with human immunodeficiency virus (HIV)
  • Known active infection with Hepatitis B virus, Hepatitis C virus or Lues.
  • Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results.
  • Have had any anti-incontinence or prolapse surgery, including the following:

    • Anterior Repair
    • Needle Suspension such as Raz; Pereyra; Stamey; Gittes; and Muzsnai procedures
    • Retropubic Procedures: such as Marshall, Marchetti & Krantz; and Burch procedures
    • Sling Procedure
    • Collagen Injections
    • Artificial Sphincter.
  • Use any of the following:

    • Any anti-incontinence device (for example, Reliance, Minigard, or FemAssist) including tampons used to prevent incontinence during participation in the study
    • Vaginal pessaries for prolapse or incontinence
    • Any nonpharmacologic intervention for incontinence or prolapse (for example, electro stimulation, vaginal cones, or any such device) within the 3 months prior to study entry.
  • Current use of any of the following drugs: antidepressants, duloxetine, monoamine oxidase inhibitors or other, clonidine, alpha-methyl-DOPA, beta-blockers, guanethidine, reserpine, pentosan polysulfate, or alpha-receptor antagonists/agonists (chronic use).
  • Current use of any medications for the treatment of urinary incontinence.
  • Are on a medication regimen including estrogens, anti-estrogens, or diuretics where dose and/or frequency has not been stable for at least the past 12 weeks, or is anticipated to change during the course of the study.
  • ≤ 30 days since receiving an investigational medicinal product or device in another clinical trial. Current enrollment in another clinical trial is not permitted.
  • Allergy/ intolerance of at least one of the active ingredients or excipients of the investigational products, e.g. bovine protein, gentamycin
  • Have any abuse disorder within the 5 years prior to study entry; e.g. patients who report regular consumption of >21 alcoholic drinks per week (an average of 3 drinks per day)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355133

Locations
Slovenia
University Medical Center Ljubljana, Dept. of Gynecology
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
University Medical Centre Ljubljana
Innovacell Biotechnologie AG
  More Information

No publications provided by University Medical Centre Ljubljana

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assoc. Prof. Adolf Lukanović, PhD, MD, Department of Gynecology, University Medical Center Ljubljana
ClinicalTrials.gov Identifier: NCT01355133     History of Changes
Other Study ID Numbers: Myoblast/ISD/EKS01, 2009-012389-30
Study First Received: May 12, 2011
Last Updated: May 16, 2011
Health Authority: Slovenia: Agency for Medicinal Products - Ministry of Health
Slovenia: Ethics Committee

Keywords provided by University Medical Centre Ljubljana:
Urinary incontinence
Myoblasts
Muscle derived cells
Stem cells

Additional relevant MeSH terms:
Urinary Incontinence
Urinary Incontinence, Stress
Urination Disorders
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on September 16, 2014