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

NCT02606201 | Completed DMC

• 1 other identifier: P130927
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Urinary Incontinence by Intrinsic Sphincter Deficiency

Keywords

stress urinary incontinence; intrinsic sphincter deficiency; myofiber; autologous; skeletal muscle precursor cells; autologous serum

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• 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

  One year after treatment

Study Arms (1)

IPSMA

EXPERIMENTAL

Injection Peri Sphincter Myofibers Autologous

Other: Peri sphincter injection Autologous myofibers

Interventions

Peri sphincter injection Autologous myofibers OTHER

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.

IPSMA

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 °
• h 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

Location

Related Publications (1)

• 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.

  PMID: 23470219 RESULT

MeSH Terms

Conditions

Urinary Incontinence, Stress

Condition Hierarchy (Ancestors)

Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• René YIOU, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: November 17, 2015
• Study Start: January 20, 2016
• Primary Completion: December 6, 2021
• Study Completion: December 6, 2021
• Last Updated: May 19, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)