Clinical trial NCT02606201: Peri-sphincter Injection of Autologous Myofibres to Treat of Urinary Incontinence by Sphincter Deficiency
Official title: Peri-sphincter Injection of Autologous Myofibres to Treat of Urinary Incontinence by Sphincter Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Incontinence by Intrinsic Sphincter Deficiency
Keywords: stress urinary incontinence
intrinsic sphincter deficiency
myofiber
autologous
skeletal muscle precursor cells
autologous serum
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-11-17
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Stress urinary incontinence related to intrinsic sphincter deficiency (ISD) is a severe form of incontinence that may have a major impact on the quality of life. The main treatment is surgical and consists in the implantation of medical devices such as the artificial urinary sphincter, adjustable continence therapy, compressive sling, or injection of bulking agent.

The investigator has developed a new therapeutic strategy for ISD that consist to implant myofibers with their attached satellite cells (the main source of muscle progenitor cells) at the vicinity of the striated urethral sphincter. The principle of this method relies on the in vivo activation of satellite cells leading to the formation of regenerated myofibers (myotubes) generating a distinct and tonic muscular activity . The proof of concept was investigated in a Phase I clinical trial: Investigator found that the periurethral implantation of myofiber strips around the urethra generated an electromyographic activity improving urethral closure pressure in women with severe urinary incontinence associated to ISD. In this previous study, the technique of myofiber implantation was invasive, as it required a surgical approach and dissection of the urethra to place the myofiber. For the clinical trial IPSMA, the investigator sought to optimize the myofiber transplantation process using a method injection of myofibers core obtained by hydro-dissection. The injection technique is performed percutaneously under fluoroscopic and endoscopic control and does not require a surgical approach of the urethra.

This clinical trial is prospective, open-label, non-randomized, uncontrolled, single-center for the first stage and multicenter for the second stage, of 13 months for each patient aims to assess the efficacy and safety of IPSMA in the treatment of urinary incontinence in women with ISD.

Detailed description: The investigator chose an assessment method in 2 stages according to the Simon plane . A total of 38 patients are needed. Assuming a ratio of 10% of lost patients or for which the primary endpoint was not evaluable, 4 additional patients will be included totaling 42 patients will be included.

This trial is single-center for the first stage and multicenter for the second stage.

11 patients will be included in the first stage and 31 patients in the second stage.

Eligibility criteria: Inclusion Criteria:

* Female.
* Age\> or = 18 years.
* Patients with stress urinary incontinence by ISD for at least 6 months Failure of Pelvic ﬂoor muscle training (at least 20 sessions).
* Fixed urethra : a negative Ulmsten test / Qtip test \<30 °
* 24h Pad test \>50 g
* Urodynamic criteria: LPP (leak points pressure) \<100 cm H20 and MUCP \<50 cm H2O replaced by Urodynamic criteria: MUCP \<50 cm H2O (amendment n°3)
* Collection of informed written consent

Exclusion Criteria:

* Not affiliated to a social security scheme
* Trouble hemostasis known
* Untreated urinary tract infection
* Muscle disease genetically determined or acquired
* Patients with urinary incontinence by vesica-urethral hypermobility
* Incomplete bladder emptying: post void residual\> 20% of the volume voided during urination\> 150cc
* Maximum urinary flow rate \<12 ml / sec replaced by maximum urinary flow rate \<12 ml / sec for volume urinated during urination \> 150cc (amendment n°3)
* overactive bladder
* Bladder capacity (B3) \<200 cc (deleted in amendment n°3)
* Urethral stricture
* Anticoagulant therapy that cannot be replaced by a low molecular weight heparin
* Pregnant or intend to become pregnant during the study period or breastfeeding informed by the patient during the consultation.

Primary outcomes:
measure: Step 1: Tolerance
timeFrame: One year after treatment
measure: Step 1 and 2: Rate of patients responder at M12 after surgery
timeFrame: One year after treatment
Secondary outcomes:
measure: Occurrence of serious and non-serious adverse events
timeFrame: One year after treatment
measure: Proportion of patients cured at M12. patients are considered as cured if: - The absence of pad use, a 24h pad test <2g AND - The absence of urinary leakage reported in the voiding diary (3 consecutive days).
timeFrame: One year after treatment
measure: Improvement of quality of life
timeFrame: One year after treatment
measure: Response times
timeFrame: One year after treatment
measure: Urodynamic evaluation
timeFrame: One year after treatment
measure: Number of re-intervention required (conventional treatment after 6 months) to treat persistent urinary incontinence after IPSMA
timeFrame: 6 months after treatment
measure: Patients with a reduction in the 24h pad test <50% at one year will be considered failure.
timeFrame: One year after treatment
measure: Direct global cost of IPSMA surgery
timeFrame: One year after treatment
measure: Healing times
timeFrame: One year after treatment
Other outcomes:
Locations:
city: Creteil
country: France
facility: Henri Mondor Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: René YIOU, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yiou R, Hogrel JY, Loche CM, Authier FJ, Lecorvoisier P, Jouany P, Roudot-Thoraval F, Lefaucheur JP. Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial. BJU Int. 2013 Jun;111(7):1105-16. doi: 10.1111/j.1464-410X.2012.11682.x. Epub 2013 Mar 7.