Vaginal Laser Therapy in Breast Cancer Survivors

Study Overview
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Brief Summary
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This study evaluates the efficacy of vaginal CO2 laser therapy in breast cancer survivors with symptoms of Genitourinary Syndrome of Menopause. Half of participants will receive active laser therapy, while the other half placebo therapy.

Official Title
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Vaginal Laser Therapy for the Management of Genitourinary Syndrome of Menopause of Breast Cancer Survivors: Double-blind Randomized Placebo-controlled Trial

Conditions
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Vaginal Atrophy, Genitourinary Syndrome of Menopause, Breast Cancer, Dyspareunia

Intervention / Treatment
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* Device: Microablative Fractional CO2 Laser Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: breast cancer history dyspareunia dryness Exclusion Criteria: 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 (The 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 Therapy<br>* 5 laser therapies intravaginally administered will be applied at monthly intervals.<br>* Other names: SmartXide2 V2LR, Monalisa Touch, DEKA, Florence, Italy;|
| Placebo Comparator: Placebo<br>Placebo therapy (The 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 Therapy<br>* 5 laser 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 | Change from baseline at 1 month post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 days voiding diary | Assesses frequency of urination, amount of urine, presence of urgency and/or urinary incontinence and amount of fluid intake | Change from baseline at 1 month post-treatment | 
| 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 | Change from baseline at 1 month post-treatment | 
| Patients Global Impression of Improvement | It is a single item questionnaire assessing the impression of participants following the intervention | At 1-month post-treatment | 
| 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 (itching, burning and dysuria) at all , while 10 symptom (itching, burning and dysuria) 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 itching, burning and dysuria | Change from baseline at 1 month post-treatment | 
| 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. | Change from baseline at 1 month post-treatment | 
| Female Sexual Function Index | It is a questionnaire defining women's sexual function. It includes 6 domains: desire, arousal, orgasm, lubrication, satisfaction and pain. The answer of each Question in each domain are multiplied by a certain factor. Total score is calculated by summing the scores of the all domains with a minimum value of 2 and a maximum of 36. The highest the total score the better is the sexual functioning. Total score above 26.55 defines normal sexual function | Change from baseline at 1 month post-treatment | 
| 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. | 6 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. | 6 months | 
| International Consultation on Incontinence Questionnaire Short Form | it is a questionnaire with 4 questions assessing the amount of leakage, frequency and type of urinary incontinence. Total score is calculated by summing the 3 out of the 4 questions. Higher scores indicate worst urinary incontinence | 6 months | 
| Modified Sexual Quality of Life Questionnaire-Male | It includes 12 questions assessing the quality of life and sexual satisfaction of the male partner. Each answer may receive values from 1 to 5. The higher the scores the better subjective evaluation of sexual quality of life | 6 months | 
| Urogenital Distress Inventory 6 | It is a condition specific questionnaire containing 6 questions. The answers of questions assesses the presence of symptoms and the degree of bother on a 4-point scale (not at all, a little bit, moderately and greatly applying to 0, 1, 2 and 3, respectively). Total score is calculated by summing the score of each question. The higher the total score the highest is the symptom bother | 6 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. | 6 months | 
| Number of blood vessels | Biopsies will be obtained from the lateral vaginal wall. Computerized determination of blood vessels number will be performed | 6 months | 
| Size of blood vessels | Biopsies will be obtained from the lateral vaginal wall. Computerized determination of the blood vessels size will be performed | 6 months | 
| Collagen | Biopsies will be obtained from the lateral vaginal wall. Determination of collagen types using immunohistochemistry and microscopy. | 6 months |