Vaginal CO2 Laser Therapy for Genitourinary Syndrome in Breast Cancer Survivors

Study Overview
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Brief Summary
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This project will be based on three studies over a period on three years. The first study is a dose response study that includes 30 breast cancer survivors. They will receive a total of 5 laser treatments with 4-6 weeks intervals The second study is a double-blind randomized controlled trial, that includes 60 breast cancer survivors. 30 of those will receive active intervention and 30 will receive placebo laser treatment and act as controls. Based on the results of the dose response study, a treatment consists of three to five laser treatments every 3 weeks. The third and last study is a one-year follow-up on study two. The conditions are evaluated before and after each treatment by questionnaires, vaginal fluid pH values, punch biopsies and vaginal and urine microbiome. The studies is conducted at the Department of Obstetrics and Gynaecology at Randers Regional Hospital in collaboration with Department of Obstetrics and Gynaecology and Department of Oncology at Aarhus University Hospital.

Official Title
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Vaginal Laser Therapy for Genitourinary Syndrome in Breast Cancer Survivors - A Randomized, Blinded, Placebo-controlled Study

Conditions
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Genitourinary Syndrome of Menopause

Intervention / Treatment
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* Device: SmartXIDE2V2LR, Monalisa Touch, DEKA, Florence, Italy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer survivor in endocrine therapy Symptomatic genitourinary symdrom of menopause with vaginal discomfort and/or dyspareunia Able to read and understand Danish Able to give written informed consent Exclusion Criteria: Pelvic organ prolapse ≥ stage 2 according to the Pelvic Organ Prolapse Quantification staging system Use of non-hormonal/hormonal vaginal therapies (1 and 12 months prior to the baseline visit, respectively) Use of Chemotherapy (6 months prior to the baseline visit) Acute urinary tract infection or active genital infection History of vaginal reconstructive surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active laser group<br>In the active laser group, participants are treated intravaginally with the fractional microablative CO2 laser system (SmartXIDE2V2LR, MonaLisa Touch, DEKA, Florence, Italy), using the following setting; dot power 30 watt, dwell time 1000 μs, dot spacing 1000 μs and the smart stack parameter from 2 to 3. At the level of the vaginal introitus, the dot power decreases to 20 Watt. | Device: SmartXIDE2V2LR, Monalisa Touch, DEKA, Florence, Italy<br>* The laser probe is gently inserted up to the top of the vagina, and subsequently withdrawn and rotated in order to deliver a complete treatment of the vaginal wall.<br>|
| Sham Comparator: Sham laser group<br>In the sham laser group, participants are treated intravaginally with the fractional microablative CO2 laser system (SmartXIDE2V2LR, Monalisa Touch, DEKA, Florence, Italy), using the following setting; dot power 0,5 watt, dwell time 100 μs, dot spacing 2000 μs and the smart stack parameter from 1 to 1 | Device: SmartXIDE2V2LR, Monalisa Touch, DEKA, Florence, Italy<br>* The laser probe is gently inserted up to the top of the vagina, and subsequently withdrawn and rotated in order to deliver a complete treatment of the vaginal wall.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal dryness | Participant are asked to complete the 10-cm visual analog scale (VAS) ranging for 0 to 10, with higher score indicating worse vaginal dryness. | Symptom data is collected at baseline visit and one month after the last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vaginal pain, itching and soreness | Evaluated with visual analog scale for vaginal pain, itching, soreness. 10-cm visual analog scale (VAS) ranging for 0 to 10, with higher score indicating worse symptoms. | Symptom data is collected at baseline visit and one month after the last treatment | 
| Female Sexual Function Index | Sexual function parameters; desire, arousal, lubrication, orgasm, satisfaction and pain. Range 2-36, the threshold of 26.55 indicates sexual dysfunction | Symptom data is collected at baseline visit and one month after the last treatment | 
| Sexual complaint screener - women | Addressing all domains of sexual dysfunction. Range 0-60, higher score indicate increased symptom severity | Symptom data is collected at baseline visit and one month after the last treatment | 
| Urogenital Distress Inventory | For urinary symptoms; irritative symptoms, obstructive/discomfort and stress symptoms. Range 0-18, higher score indicate higher disability | Symptom data is collected at baseline visit and one month after the last treatment | 
| International Consultation on Incontinence Questionnaire Female Urinary Tract Symptoms Sex | Evaluation of female sexual matters associated with their lower urinary tract symptoms. Range 0-14, higher values indicating increased symptom severity. | Symptom data is collected at baseline visit and one month after the last treatment | 
| Vaginal health index | subjective scoring of moisture, fluid volume, epithelial integrity and elasticity and objective scoring of pH. Range 5-25, higher scores indicate better health | Vaginal health index is evaluated at baseline visit and one month after the last treatment | 
| Vaginal biopsy | The biopsy of 4*4 mm is taken from the lateralt vaginal wall, 2-3 cm from inotroitus. Afterwards fixated i formalin and the processed for light microsopy by a specialized gynaecological pathologist reporting on the changes in the histology of vaginal epithel and lamina propria. | Vaginal biopsy is collected at baseline visit and one month after the last treatment | 
| Vaginal and urinary microbiota | One polyester swap (FLOQSwab) is used to sample mid-vagina for microbial analysis and immediately been placed at - 80 °C until further processing. Urine is collected in a 50 mL collection tube using the clean catch method for women. Afterwards aliquoted into 10 mL fractions and immediately been placed at - 80 °C until further processing. DNA is isolated from samples using standard DNA isolation kits and microbiota composition determined using 16S rRNA gene sequencing. Microbiota composition is compared between groups and over time based on alpha- and beta-diversity measures, as well as changes in relative abundances of individual bacteria. | Vaginal and urine microbiota are collected at baseline visit and one month after the last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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laser, mamma cancer