Peri-sphincter Injection of Autologous Myofibres to Treat of Urinary Incontinence by Sphincter Deficiency (IPSMA)

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.

Study Overview

• Status: Completed
• Conditions: Urinary Incontinence by Intrinsic Sphincter Deficiency
• Intervention / Treatment: Other: Peri sphincter injection Autologous myofibers

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Henri Mondor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IPSMA; Injection Peri Sphincter Myofibers Autologous

Other: Peri sphincter injection Autologous myofibers; The first step of the procedure consists to harvest a muscle fragment from the lower part of the rectus abdominis muscle of the abdomen approached by a short incision. Injectable myofiber cores will be prepared by hydrodissection of the muscle biopsy. All myofibers cores will be suspended in autologous serum prepared by centrifugation before the incision. During the second step of the procedure, the myofibers will be injected percutaneously into the peri-sphincter region under endoscopic and radiographic control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Step 1: Tolerance	- Tolerance: Serious adverse events grade 3 or more related to the procedure according to Data Safety and Monitoring Board (DSMB)	One year after treatment
Step 1 and 2: Rate of patients responder at M12 after surgery	Efficiency: Response is defined by an improvement in 24h pad weight as greater than 50% reduction from baseline and improvement in the number of incontinence episodes per day as greater than 50% reduction from baseline	One year after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of serious and non-serious adverse events		One year after treatment
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).		One year after treatment
Improvement of quality of life		One year after treatment
Response times		One year after treatment
Urodynamic evaluation	Leak Point Pressure (LPP), maximal urethral closure pressure (MUCP), area under the curve (profilometry), electromyogram (EMG) gives urodynamic evaluation	One year after treatment
Number of re-intervention required (conventional treatment after 6 months) to treat persistent urinary incontinence after IPSMA		6 months after treatment
Patients with a reduction in the 24h pad test <50% at one year will be considered failure.		One year after treatment
Direct global cost of IPSMA surgery		One year after treatment
Healing times	Defined by : The absence of pad use, a 24h pad test <2g AND; The absence of urinary leakage reported in the voiding diary (3 consecutive days).	One year after treatment

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: René YIOU, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2016
• Primary Completion (Actual): December 6, 2021
• Study Completion (Actual): December 6, 2021

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: November 13, 2015
• First Posted (Estimate): November 17, 2015

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: stress urinary incontinence; autologous; autologous serum; intrinsic sphincter deficiency; myofiber; skeletal muscle precursor cells
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Elimination Disorders; Urinary Incontinence; Enuresis
• Other Study ID Numbers: P130927

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWNED BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION