Histological Modifications of Postmenopausal Vaginal Mucosa After Repeated Carbon Dioxide (CO2) Laser Treatment (REPLAMOD)

Histological Modifications of Postmenopausal Vaginal Mucosa After Repeated CO2 Laser

To assess the long-term histological and clinical efficacy of MonaLisa Touch procedure for the management of the Genitourinary Syndrome of Menopause (GSM) in postmenopausal female patients.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy; Breast Cancer Female; Dyspareunia
• Intervention / Treatment: Device: SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy

Detailed Description

The investigator propose a prospective case series of 15 postmenopausal women with bothersome symptoms of GSM treated with MonaLisa Touch CO2 laser. The investigator hypothesize that even in the long term MonaLisa Touch will significantly improve GSM histologically and clinically from baseline.

The primary outcome objective of the study is to evaluate the histological modifications of the vaginal mucosa after repeated CO2 Monalisa Touch laser treatment. The investigator shall evaluate the role of this treatment by calculating the difference in vaginal epithelial thickness between the biopsy obtained before the start of laser treatment and the biopsy obtained after treatment. In addition, the study will analyze the safety of repeated laser treatments verifying the absence of fibrosis formation in the vaginal mucosa. Secondary objectives of the study will include an evaluation of the clinical effects associated with repeated Monalisa Touch CO2 laser treatments using validated questionnaires.

All participants will be screened to ensure inclusion/exclusion criteria are met. A biopsy will be taken from each patient one month before the first laser treatment and one month after the last laser treatment. The MonaLisa treatment will be performed monthly for 3 months. MonaLisa treatment with fractional microablative laser system. For subjects with concomitant vulvar symptoms, vulvar treatment will be done. Biopsy samples will be analyzed with Hematoxylin- Eosin and Trichrome staining, Periodic acid-Schiff (PAS) reaction for glycogen and immunohistochemistry for CD34, a vessel marker. All clinical questionnaires will be assessed at baseline and at one month after the last session.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • IRCCS San Raffaele Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Italian speaking and able to give informed consent.
• Menopausal females with absence of menstruation for at least 12 months.
• Presence of GSM symptoms.
• Completion of at least two cycles of three laser treatments sessions in previous years.
• Prolapse stage < II, according to the pelvic organ prolapse quantification (POP-Q) system.
• No pelvic surgery within 6 months prior to treatment.
• Understanding and acceptance to the obligation to return to all scheduled visits and follow-ups.

Exclusion Criteria:

• Inability of give informed consent
• History of vulvovaginal condyloma, vaginal intraepithelial neoplasia (VAIN), vaginal carcinoma, lichen sclerosis, lichen planus.
• History of cancers of the lower genital tract (cervix, uterus, vagina).
• History of pelvic radiotherapy.
• Personal history of genital fistula, a thin recto-vaginal septum as determined by the investigator or personal history of a fourth degree laceration during screening physical exam.
• Any other medical condition that the investigators feel would compromise the study.
• Acute or recurrent urinary tract infection (UTI), or genital infection (e.g. bacterial vaginosis, herpes genitalis, candida).
• Stage III or IV pelvic organ prolapse.
• History of any female sexual disorder.

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: Patient; All participants will be screened to ensure inclusion/exclusion criteria are met. A biopsy will be taken from each patient one month before the first laser treatment and one month after the last laser treatment. The MonaLisa treatment will be performed monthly for 3 months. A clinical evaluation will be recorded for each patient using validated questionnaires at baseline and one month after the last procedure.

Device: SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy; SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy; MonaLisa Touch CO2 fractionated laser

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microscopic evaluation for vaginal epithelial thickness	The vaginal epithelial thickness will be measured in micrometers. Then the difference in vaginal epithelial thickness between the biopsy obtained before and after the start of laser treatment will be calculated, considering a 20% increase as significant.	4-5 weeks after the last treatment
Microscopic evaluation of number of papillae	The number of papillae in bioptic samples will be analyzed with Hematoxylin- Eosin and Trichrome staining.	4-5 weeks after the last treatment
Microscopic evaluation of glycogen amount	The amount of glycogen present at the epithelial level and the ratio between the number of type I collagen fibers and type III will be evaluated with PAS reaction for glycogen.	4-5 weeks after the last treatment
Microscopic evaluation of number and size of the vessels	The number and size of the vessels present in the subepithelial layer will be evaluated using immunohistochemistry for CD34, a vessel marker.	4-5 weeks after the last treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validated questionnaires VHI	Vaginal Health Index (VHI) for evaluation of vaginal atrophy severity that is composed by the sum of 6 fields (min score 1 max score 5). The least score (6) is the worst; the maximum score (30) is the best.	4-5 weeks after the last treatment
Validated questionnaires FSFI	Female Sexual Function Index (FSFI) questionnaire which will assess female sexual function that is composed of 19 fields. The minimum score is 2 in the worst situation; maximum score is 36 in the best situation	4-5 weeks after the last treatment
Validated questionnaires UDI-6	Urinary Distress Inventory-6 (UDI-6) is a 6 fields questionnaires on voiding function. The minimum score is 0 in absence of symptoms; 18 is the maximum score in the worst situation.	4-5 weeks after the last treatment
Validated questionnaires ICIQ-UI	International Consultation on Incontinence Questionnaire - Urinary Incontinence (ICIQ-UI) which will evaluate the extent of urinary symptoms. It is divided into two parts: questions 1, 2 and 3 are added together and the maximum score is 22, in worst condition; a score of zero is obtained in asymptomatic patients. The last is a describing question.	4-5 weeks after the last treatment
Validated questionnaires LIKERT	5-point Likert scale is made to assess the impact of GSM symptoms on quality of life (QoL). It is a descriptive question.	4-5 weeks after the last treatment

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Investigators: Principal Investigator: Stefano Salvatore, MD, IRCCS San Raffaele Hospital

Publications and helpful links

General Publications

• Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013 Sep;20(9):888-902; quiz 903-4. doi: 10.1097/GME.0b013e3182a122c2.
• Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligaro A. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015 Jan;30(1):429-36. doi: 10.1007/s10103-014-1677-2. Epub 2014 Nov 20.
• Salvatore S, Nappi RE, Zerbinati N, Calligaro A, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric. 2014 Aug;17(4):363-9. doi: 10.3109/13697137.2014.899347. Epub 2014 Jun 5.
• Cagnacci A, Xholli A, Sclauzero M, Venier M, Palma F, Gambacciani M; writing group of the ANGEL study. Vaginal atrophy across the menopausal age: results from the ANGEL study. Climacteric. 2019 Feb;22(1):85-89. doi: 10.1080/13697137.2018.1529748. Epub 2019 Jan 2.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2019
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: November 27, 2020
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 10, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Dyspareunia
• Other Study ID Numbers: REPLAMOD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No