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

Phase 1
Completed
Conditions
Stress Urinary Incontinence
Registration Number
NCT01355133
Lead Sponsor
University Medical Centre Ljubljana
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
40
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Change from baseline in Incontinence episode frequency (IEF)6 months post-implantation

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 score6 months post-implantation

Mean improvement from baseline for the Incontinence Quality of Life (I-QOL) total score

Change from baseline in the Incontinence score6 months post-implantation
Secondary Outcome Measures
NameTimeMethod
Time to onset of responseUp to 6 months post-implantation (based on recordings at baseline, at implantation, at 6 weeks, 3 months and 6 months post-impalntation)

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 outcomeBaseline, 6 months postimplantation.
Rate for subsequent incontinence surgery6 months post-implantation
Change from baseline in Urodynamic evaluation6 months post-implantation

Cystometry, urethral pressure profile (UPP), 1-hour pad-test.

SafetyUp to 6 months post-implantation

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)6 months post-implantation

Amount of leaked urine measured semiqantitative from a 3-day bladder diary.

Trial Locations

Locations (1)

University Medical Center Ljubljana, Dept. of Gynecology

🇸🇮

Ljubljana, Slovenia

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