Vaginal CO2 Laser and the Genitourinary Syndrome of Menopause

Study Overview
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Brief Summary
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This study evaluates the clinical, histopathological, cytological and microbiological efficacy of Microablative Fractional CO2 laser intravaginally administered in postmenopausal women with Genitourinary Syndrome of Menopause. Half participants will receive active CO2 laser therapy, while the other half will receive placebo CO2 laser therapy.

Official Title
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The Clinical, Histopathological, Cytological and Microbiological Efficacy of the Micro-ablative Fractional CO2 Laser : A Double-blind Randomized Placebo-controlled Trial

Conditions
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Vaginal Atrophy

Intervention / Treatment
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* Device: Microablative Fractional CO2 laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of vaginal atrophy (dyspareunia and/or vaginal dryness) Menopause Exclusion Criteria: Systemic or local hormonal therapy the last 6 months Use of moisturizers or lubricants the last month Active genital infection (i.e herpes, vaginitis) Prolapse stage >=2 Underlying pathologies that could interfere with the protocol compliance
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laser Group<br>Microablative Fractional CO2 laser therapy at monthly intervals. The laser parameters that will be used are the following: (1) Power: 30 ή 40 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter from 1-3 depending on the treatment status, 5) D-pulse mode. | Device: Microablative Fractional CO2 laser<br>* 3 therapies intravaginally administered will be applied at monthly intervals<br>* Other names: SmartXide2 V2LR, Monalisa Touch, DEKA, Florence, Italy;|
| Placebo Comparator: Placebo Group<br>Placebo CO2 laser therapies at monthly intervals. The laser parameters that will be used are the following: 1) Power: 0.5 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter 1, 5) Smart-pulse mode. | Device: Microablative Fractional CO2 laser<br>* 3 therapies intravaginally administered will be applied at monthly intervals<br>* Other names: SmartXide2 V2LR, Monalisa Touch, DEKA, Florence, Italy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10-centimeter Visual Analogue Scale assessing intensity of dyspareunia and dryness | It is a straight line with 2 endpoints 0 and 10. Zero defines no dyspareunia at all and no dryness at all , while 10 dyspareunia as bad as it could be and dryness as bad as it could be. Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of dyspareunia and dryness | 24-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day-to Day Impact of vaginal aging questionnaire (DIVA) | It includes 4 domains: activities of daily living (5 items), sexual functioning (5 items), emotional well-being (4 items), self-concept and body image (5-items). Each item of each domain could receive values from 0 to 4. Mean scores are calculated on each of the domain scales. Higher scores indicate greater symptom impact | 24 months | 
| Patients Global Impression of Improvement | It is a single question with 7 possible answers. Patients will chose the answer that applies at their impression of improvement after the laser therapy | 24 months | 
| 10-centimeter Visual Analogue Scale assessing intensity of itching, burning and dysuria | It is a straight line with 2 endpoints 0 and 10. Zero defines no symptom at all, while 10 symptom as bad as it could be and dryness as bad as it could be. Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of symptom | 24 months | 
| 3 days voiding diary | Assesses bladder function (frequency, urgency and incontinence) | 24 months | 
| Female Sexual Function Index | It includes 6 domains assessing sexual functioning (desire, arousal, orgasm, lubrication, satisfaction and pain). Total score is calculated by summing scores of the 5 domains multiplied by certain factors with a minimum value of 2 and maximum 36 | 24 months | 
| International Consultation on Incontinence Questionnaire Short Form/Female Lower Urinary tract Symptoms (ICIQ-FLUTS) | It is a 12-items questionnaire evaluating nocturia, urgency, bladder pain, frequency, hesitancy, straining, intermittency, urinary incontinence (urge, stress and unexplained), frequency of urinary incontinence and nocturnal enuresis. Filling, voiding and incontinence symptoms subscales range from 0 to 15, 0 to 12 and 0 to 20, respectively. | 24 months | 
| King's Health Questionnaire (KHQ) | It has 3 sections: 1) general health and overall health related to urinary symptoms with 2 questions, 2) incontinence impact, role limitations, physical limitations, social limitations, personal limitations, emotions, sleep and energy, and severity coping measures with 19 questions and 3) bother or impact of urinary symptoms with 11 questions. Scores of each domain of the 2 sections range from 0 to 100. Scores of the third section range from 0 to 3. Higher scores indicate higher impact of urinary incontinence. | 24 months | 
| Vaginal Maturation Value | It is calculated by defining the percentage of superficial, intermediate and parabasal epithelial cells on the vaginal pap smear, following the formula (1x%superficial)+(0.5x%intermediate)+(0x%parabasal). It may receive values from 0 to 100%.It is considered to be an indicator of the estrogenic stimulation, whereas values of 0-49%, 50-64% and 65-100% indicate absent/low, moderate and high estrogenic effect on the vaginal epithelium, respectively. | 24 months | 
| Vaginal Health Index Score | It evaluates vaginal elasticity, fluid volume, ph of vaginal fluid, epithelial integrity and moisture. Each one of these may receive scores from 1 to 5. Total score is calculated by summing the 5 scores ranging from 5 to 25. Higher scores indicate better vaginal status. | 24 months | 
| Epithelial thickness | Biopsies will be obtained from the lateral vaginal wall. Epithelial thickness (in μ) will be measured by a vertical line between basal layer cells and superficial layers. | 24 months | 
| Number of Blood vessels | Computerized determination of number of capillary profiles in the test area will be performed percent of total area of subepithelial stroma), will be performed. | 24 months | 
| Size of blood vessels | Computerized determination of diameter (in μ), length (in μ) αnd width (in μ) will be performed. | 24 months | 
| Density of blood vessels | Computerized determination of volume density of blood vessels in percent of total area of subepithelial stroma will be performed | 24 months | 
| Cultures of vaginal samples | Lactobacilli, aerobic bacteria, anaerobic bacteria, fungi will be evaluated | 24 months | 
| Polymerase Chain Reaction | Lactobacilli, bacteria and fungi will be evaluated. | 24 months |