Photobiomodulation in Post Menopause Genitourinary Syndrome

Study Overview
=================
Brief Summary
-----------------
The goal of this project is to evaluate the clinical response of patients with symptoms of genitourinary menopause syndrome after the application of photobiomodulation in the vagina and its introit. METHOD: In this randomized, double-blind, placebo-controlled study protocol, women over 50 years of age who are in the postmenopausal period (amenorrhea for at least 12 months, with no pathology involved) with one or more symptoms of PGS will be selected. Participants included in the study will be randomly divided into two groups: group A, which will receive photobiomodulation with a vaginal diode laser and its introit and group B (placebo) with the laser device turned off. Both treatments will be maintained for 4 consecutive weeks.The treatment group (n=30) will receive four consecutive applications, using laser diode DMC (808 nm), 4J per point, 100mW of power, 510mW/cm², beam area of 0.2cm², 8 sites in the external vagina, for the 40s in each site, once per week for 4 weeks. The Placebo Group (n=30) will be handled as treated, but with the laser turned off. Quality of life will be analyzed using the female sexual functioning index (FSFI-6), the urinary incontinence questionnaire (ICIQ-SF), the intensity of menopausal symptoms will be evaluated using a visual analogue scale (VAS), the vulvo vaginal atrophy will be measured by the Vaginal Health Index (VHI) and compared between groups. Also, the vaginal temperature will be measured using a thermal camera, as well as the pressure of the pelvic floor force (vaginal dynamometer) and a 1-hour Pad Test will be performed to quantify the urinary loss. The data will be tested for normality using the Shapiro Wilks test and, if they present a parametric distribution, they will be represented by means of their respective means and standard deviations.

Official Title
-----------------
Photobiomodulation in Post Menopause Genitourinary Syndrome - Study Protocol for a Randomized, Double-blind, Controlled Clinical Trial

Conditions
-----------------
Postmenopausal Symptoms

Intervention / Treatment
-----------------
* Radiation: Photobiomodulation
* Radiation: Placebo Photobiomodulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women over 50 years of age who are in the postmenopausal period (amenorrhea for at least 12 months, with no pathology involved); With one or more symptoms of UGS (dyspareunia, dryness, irritation and vaginal burning and/or discomfort, vaginal atrophy, vaginal and vulvar dryness, dysuria, frequency, recurrent urinary infections); With complaints of stress and/or urge urinary incontinence; Who have cervical cytopathology (Pap smear) within the normal range performed in the last year and are not in use of hormonal medication to treat menopausal symptoms in the last 6 months. Exclusion Criteria: Participants with explicit refusal of the patient to participate in the researc; History of bilateral oophorectomy and diseases such as: recent AMI (Acute Myocardial Infarction), neoplasms, history of thrombosis, liver failure, uncontrolled genital bleeding, genital condylomatosis, active genital herpes, lower genital tract surgeries that make treatment impossible.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Photobiomodulation group<br>Participants in this group will receive photobiomodulation with a vaginal diode laser and its introit. | Radiation: Photobiomodulation<br>* The treatment group will receive four consecutive applications, using laser diode DMC (808 nm), 4J per point, 100mW of power, 510mW/cm², beam area of 0.2cm², 8 sites in the external vagina, for 40s in each site, once per week for 4 weeks.<br>|
| Placebo Comparator: Placebo group<br>Participants in this group will receive simulated photobiomodulation, with the laser device turned off. | Radiation: Placebo Photobiomodulation<br>* The Placebo Group will receive the same four consecutive applications, but with the laser turned off.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Female Sexual Function Index (FSFI) | The FSFI or female sexual function index is a specific and multidimensional questionnaire to assess female sexual response, accessing 6 domains: desire, arousal, lubrication, orgasm, satisfaction and pain evaluated in 19 questions about sexual activity in the last 4 weeks. In order to obtain the total score of the scale, the scores for each domain are added up, and for higher scores, better sexual function is considered, and the threshold for sexual dysfunction is a score of 2678. Based on the value of the total score, it would be possible discriminate between populations at higher and lower risk of experiencing sexual dysfunction. | Baseline and the 4 weeks of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) | This questionnaire has a score from zero to 21 points, with zero indicating the absence of symptoms and the greater the sum of the points, the greater the impact and severity of urinary incontinence (UI) symptoms. The maximum sum of the response values indicates a score of 21 points, referring to a high impact of UI on the individual's life. | Baseline and the 4 weeks of treatment. | 
| Changes in the Vaginal Health Index Score | It consists of a clinical analysis during the speculum examination of 5 parameters: elasticity, pH, mucosal appearance, humidity and the presence of vaginal secretion. Each aspect evaluated receives a score, which varies from 1 to 5. The score may vary from 5 to 25, and a diagnosis of Vulvo Vaginal Atrophy (VVA) is considered when the values are less than or equal to 15, the maximum score of 25 points means absence of clinical signs of vulvovaginal atrophy. This assessment will be performed by a qualified professional during the physical examination. | Baseline and the 4 weeks of treatment. | 
| Changes in the Vaginal pH | The evaluation of the vaginal pH will be carried out through a pH indicator strip, which when inserted in the middle third of the vagina in contact with the mucosa, has the color of the strip changed. Measurement of the vaginal cul-de-sac is avoided, because contact with mucus, blood or semen can alter the reading. The nitrazine tape must remain in contact with the vaginal wall for 5 seconds for later checking the pH on the colorimetric scale provided by the manufacturer. Normal vaginal pH is acidic, during menacme, it should be maintained between 3.8 and 4.5. | Baseline and the 4 weeks of treatment. | 
| Changes in Pain using a Visual Analog Scale (VAS) | A VAS will be used to evaluate the vaginal complaints of the participants. They will receive a figure of a ruler with marks from 0 to 10, whose one end indicates complete absence of symptoms and the other indicates the worst possible symptom. For analysis of the Visual and Analog Scale of Symptoms of Genitourinary Syndrome (GUS) (VAS - SGU), the sum of one to twelve points will classify the symptoms from mild to severe. | Baseline and the 4 weeks of treatment. | 
| Changes in the Pelvic Floor Muscles (PFMs) | The pressure sensor (dynamometer) will be introduced into the vaginal canal, and the resting vaginal pressure (resting muscles) will be quantified. The device will be calibrated, zeroed and it will be asked for the participant to contract their PFMs inwards and upwards as hard as possible 3 times and maintain the contraction for at least five seconds (maximum vaginal pressure), with an interval of 30 seconds between each pull. | Baseline and once a week for 4 weeks | 
| Changes in Urinary Loss using Ped-Test | The procedure for performing the Ped-test will be as follows: initially, the participant will be asked to place an absorbent with a previously measured weight close to the external urethral meatus. Then, she will be given a 500 mL bottle of water to drink and wait for 15 minutes. Afterwards, the participant will be asked to perform some actions simulating activities of daily living. After carrying out the proposed activities, the absorbent will be removed and weighed on a precision scale, with a minimum reading of 0.1 mg and a maximum capacity of 220 g. Urinary losses are evaluated and classified as follows: losses of up to 1 g are considered insignificant; between 1.1 and 9.9 g are classified as light losses; between 10 and 49.9 g are moderate losses; and above 50 g, severe losses. | Baseline, the 4 weeks of treatment and 90 days after treatment. | 
| Changes in Vulva Temperature | The temperature of the vulva, in Celsius degrees, will be evaluated at the eight points of radiation in the vulvar region, with a digital infrared thermometer, which will allow measurement without physical contact. The average of the eight readings will be calculated before and after the diode laser procedure in the 4 consecutive weekly sessions. | Baseline and and once a week for 4 weeks |