Clinical trial NCT03947164: iMEA : Comparison of Micro-innervation and Muscle Microstructure of the Anal Levator Muscle Between Patients With Urogenital Prolapse and Those Who Are Asymptomatic
Official title: iMEA : Comparison of Micro-innervation and Muscle Microstructure of the Anal Levator Muscle Between Patients With Urogenital Prolapse and Those Who Are Asymptomatic
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prolapse Genital
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2019-05-13
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monocentric case-control study (1: 1). The inclusion of cases and controls will be prospective. For each case, a control will be included with matching on parity (0, at least one child). Concerning the age, they will be matched according to the following age groups: 18-39 years old, 40-44 years old, 45-49 years old, 50-54 years old, over 55 years old.
Primary purpose: OTHER

Brief summary: Pelvic organ prolapse (POP) is defined by the International Continence Society (ICS) as a downward displacement of one or several of the followings: "the anterior wall of the vagina", "the posterior wall of the vagina" or "the cervix".

Principal risk factor of the POP is the muscular trauma of the Levator Ani Muscle (LAM) or pelvic nerve injury during vaginal delivery and pregnancy. The POP is a real public health problem. Nearly a quarter of the female population will be affected by this pathology during their lifetime. Also, the POP is responsible for impaired quality of life. POP management is mainly surgical. The LAM is classically described as a striated muscle. In an anatomic study based on female human fetuses, it has been described a new representation of nerve supplying LAM innervation with both autonomic and somatic participation. In a second study, it has been observed within the LAM, a visceral medial area (interface with the pelvic viscera) composed of smooth muscle cells under autonomic nervous control and a lateral parietal area (interface with the bone basin) composed of striated muscle cells under somatic control. Because of the medial localization of these smooth muscle areas, it is hypothesed that the visceral medial zone within the LAM plays a major role in pelvic status maintaining.

The main goal is to compare the proportion of smooth muscle cells within the MEA in patients with urogenital prolapse and in asymptomatic ones.

The secondary objectives are:

* To compare the expression of neurotransmitters within smooth muscle cell areas in patients with POPs and asymptomatic patients.
* To compare the proportion of striated muscle cells in MEA in patients with POPs and asymptomatic patients.

Detailed description: It is a monocentric case-control study (1: 1). The inclusion of cases and witnesses will be prospective. For each case, a witness will be included with matching on parity (0, at least one child). Concerning the age, they will be matched according to the following age groups: 18-39 years old, 40-44 years old, 45-49 years old, 50-54 years old, over 55 years old.

For cases and controls, before the intervention, a questioning (age, weight, height, parity, mode of delivery, hormonal status), clinical symptoms of POPs and urinary incontinence, a detailed clinical examination, and an urodynamic assessment (in case of POPs) will be noted.

All cases and controls will have an ultrasound guided MEA biopsy. A fine needle will be used. The biopsy (5mm) will interest the medial part located between the vagina and the rectum.

Patients will be seen on post-operative visits between 15 days and 2 months after surgery for an examination and clinical examination.

From the biopsy, it will be performed a classic staining (Masson's trichrome) and specific immuno-markings to detect all the nerves, and to differentiate parasympathetic autonomic, sympathetic autonomic, erectile, and somatic nerves. Immunostaining for smooth muscle, striated muscle and relaxin system will also be performed. An immunofluorescence technique will be associated. Thus, some additional slides will be reserved for an actomyosin ATPase enzymatic reaction to differentiate muscle fiber types. Treated sections will be digitized with a Hamamatsu slide scanner for subsequent image analysis and analysis. The size of the different types of striated muscle fibers (1, 2a, 2b) will be measured using the NDPview (Hamamatsu) software. The labeling surface of the different antibodies will be quantified objectively by the NIS-Elements Viewer software.

Benefits are collective :

1. Clinical impact: Find new medical therapeutic targets and improve rehabilitation techniques.
2. Repercussion in research:

   * To set up a PHRC with a randomized controlled multicenter study on the comparison of electrical stimulation and voluntary muscular contraction in postpartum with measurement of pelvic floor muscle strength and pelvic-perineal evaluation (search for pelvic prolapse , urinary incontinence).
   * To improve knowledge of anatomy and physiology of pelvic floor muscles by mapping neurotransmitters in LAM in adult patients with POPs and asymptomatic patients.

Eligibility criteria: Inclusion Criteria:

Case :

- Patient operated at Rennes University Hospital of anterior POP and / or posterior POP via vaginal and / or abdominal way.

POPs will be classified in stages 2-4 using the ICS classification;

* Without urinary incontinence associated effort (eliminated by the interrogation);
* Registered to a health insurance system;
* Having received information on the protocol and giving informed written consent.

Control :

For each case, a witness will be included with matching on the 5 year age group and parity (0, at least one child). It will be :

* Patient operated at the Rennes University Hospital for a vaginal or abdominal hysterectomy for a benign reason.
* No POPs and no urinary incontinence eliminated during the interrogation and clinical examination.
* Registered to a health insurance system;
* Having received information on the protocol and giving informed written consent.

Exclusion Criteria:

Case and Control : Exclusion criteria:

* Pregnant or lactating women
* Patients with pelvic endometriosis, pelvic gynecological cancer, history of hysterectomy.
* Major person subject to legal protection (safeguard of justice, guardianship, tutorship), deprived of liberty.
* Participation in another research involving the interventional human person or at minimal risk and constraint

Primary outcomes:
measure: Proportion of smooth muscle cells
timeFrame: inclusion visit
Secondary outcomes:
measure: Immunolabeling of the parasympathetic (cholinergic) nervous system 31
timeFrame: inclusion visit
measure: Identification of nerve fibers
timeFrame: inclusion visit
measure: Immunolabeling of the sympathetic nervous system (noradrenergic) 31
timeFrame: inclusion visit
measure: Immunolabeling of anti-neuronal Nitric Oxide Synthase (nNOS) 32
timeFrame: inclusion visit
measure: Immunolabelling of the somatic nervous system anti-PMP2233
timeFrame: inclusion visit
measure: Proportion of striated muscle cells in MEA
timeFrame: inclusion visit
Other outcomes:
Locations:
city: Rennes
country: France
facility: Rennes University Hospital
state: Bretagne
Study officials:
affiliation: Rennes University Hospital
name: 02.99.28.43.21 Nyangoh Timoh, MD
role: PRINCIPAL_INVESTIGATOR
References: