Clinical trial NCT04735549: Vulvovaginal Atrophy Correction Using Neodymium Laser
Official title: Correction of Vulvovaginal Atrophy in Postmenopausal Women Using Neodymium Laser Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopausal Period
Vaginal Atrophy
Female Urogenital Diseases
Keywords: Vaginal Atrophy
Female Urogenital Diseases
Neodymium Laser
Laser Treatment
Nanosecond
Laser
Vaginal
Postmenopausal
Lead sponsor: MeLSyTech, Ltd
Sponsor class: INDUSTRY
First posted: 2021-02-03
Enrollment: 120
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The aim of this prospective study is characteristic of changes in the vaginal wall and vulva after treatment of neodymium laser radiation with a wavelength of 1064 nm. To assess the condition of the vaginal walls and vulva before and after laser treatment, the following methods will be used: vaginal health index, perineometry, elastography of vulva, cytological methods. Female Sexual Function Index (FSFI), The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Vulvovaginal Symptoms Questionnaire (VSQ), Visual Analogue Scale (VAS) will be used to collect feedback on changes in the participants life quality. Total up to 120 participants with postmenopausal atrophy will be involved in the study. Participants will be divided into three groups: laser treatment group, topical hormones treatment group, and both laser treatment with topical hormones application group, by 40 participants in each. The time intervals between tests will be the same for all groups. Thus, a direct comparison between conventional treatment (topical hormones), laser treatment and combine laser and topical hormones therapy of the vaginal atrophy will be made. The main hypothesis of the study is improvement in condition of the vaginal walls after laser treatment and laser treatment with hormones application compared with the initial state of not less than thirty percent of participants, and improvement in condition on average compared with the hormones only therapy group.

Detailed description: The principle of participant distribution into groups is the main method of treatment of postmenopausal vaginal atrophy. Total up to 120 participants with postmenopausal atrophy will be involved in the study. Participants will be divided into three groups: laser treatment group, topical hormones treatment group, laser treatment with topical hormones application, by 40 participants in each.

The types of examination of each group are the same and include:

General methods: physical examination, clinical blood analysis with glucose determination, clinical urine test, vaginal smear for flora and oncocytology, pelvic ultrasound.

Special methods: filling out the questionnaire (Female Sexual Function Index, The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, Vulvovaginal Symptoms Questionnaire), Vaginal Health Index determination, Visual Analogue Scale (VAS) determination, perineometry, vaginal smear for cytology, elastography of vulva, microbiological vaginal smear stained by Gram.

The treatment procedure of this study is the laser treatment of the vagina and vulva with a "Magic Max" laser ("Magic Gyno" from August 2024) with subsequent monitoring.

Treatment Technique:

Laser treatment procedure will be carried out in three stages. In total, three procedures will be performed with an interval of 4-6 weeks. Two follow-up visits will follow: 1 and 6 months after the last procedure.

During the procedure, the following sequence of actions will be performed:

1. st Stage - vaginal processing with a conical mirror handpiece,
2. nd Stage - vaginal processing with a corner mirror handpiece,
3. rd Stage - external vulva and paraurethral region processing with a switched beam diameter handpiece.

Laser radiation is emitted by a series of pulses following each other through a pause. The duration of one pulse is 20-200 nanoseconds (ns), the pause between pulses is 30 microseconds (us). The energy of one pulse is about 1 millijoule (mJ). The procedure is performed without anesthesia. The doctor always focuses on the participant's feeling of warmth.

Hormone treatment procedure. Local hormone therapy with estriol will be used as a therapeutic tool for the control group. The course of treatment will be of 2 weeks of daily use, and then a maintenance therapy will be used of 2 times a week for 12 months to prevent symptoms.

Participants of all groups will be tested with the general methods necessary to include the participant in the study at the first visit.

For the laser treatment group: Studies will be carried out using special methods and then laser treatment of the vagina and vulva and paraurethral region will be performed during the 2nd, 3d, and 4th visits. Studies with all special methods will be performed during the 1st (before the start of treatment) visit. Vaginal health index, pH-measurement, perineometry, and filling of questionnaires will be performed during 3d-6th visits. Cytological investigation and elastography of vulva will be performed during 5th (1 month after the last procedure) and 6th (6 months after the last procedure).

For the hormone treatment group: Studies with all special methods will be performed during the 1st (before the start of treatment) visit. Vaginal health index, pH-measurement, perineometry, and filling of questionnaires will be performed during 3d-6th visits. Cytological investigation and Doppler sonography will be performed during 5th (1 month after the last procedure) and 6th (6 months after the last procedure). Hormone therapy will begin from the 2nd visit. All subsequent visits will be carried out at the same time intervals as for the laser treatment group, using studies with special methods. The 3d visit will be in 4-6 weeks after the start of treatment, the 4th will be in 4-6 weeks after the 3d visit, the 5th - 1 month after the 4th, the 6th - 6 months after the 4th.

For the combine laser treatment with topical hormones application group: laser treatment of the vagina and vulva and paraurethral region will be performed during the 2nd, 3d, and 4th visits. At the same time, starting from 2nd visit hormone therapy will be started. All subsequent visits will be carried out at the same time intervals as for the laser treatment group and hormone treatment group, using studies with special methods.

Thus, a direct comparison between conventional treatment (topical hormones), laser treatment and combine therapy of the vaginal atrophy will be made during the treatment, as well as on follow-up visits in 1 and 6 months after the end of each type of treatment.

The study will be carried out with the participation of FSBI "National Medical Research Center For Obstetrics, Gynecology And Perinatology Named After Academician V.I.Kulakov" MINISTRY OF HEALTHCARE OF THE RUSSIAN FEDERATION

All data obtained during the study will be transferred to the manufacturer of "MeLSyTech" Ltd.

The study will be monitored by "MeLSyTech" Ltd as follows:

* Once a month, monitoring of provided documents (copies of individual registration records of participants, informed consent, test results) for the complete filling of the forms; the clarity of filling out forms, the possibility of systematizing information from the forms of their assessment;
* Once every six months, monitoring will be conducted with a coordinator visit of the research center and analysis activities, such as participants recruitment, data collection, data management, data analysis, reporting for adverse events, and change management;
* Once a year, the investigator submits a clinical evaluation report to the sponsor.

Statistics

The analysis will be carried out both between groups of participants receiving different types of therapy (analysis of independent groups) and within groups at different time intervals (analysis of matched groups).

Before performing statistical analysis of the data, the distribution type of the variables will be assessed. To assess the normality of distribution for each variable, histograms of frequency distributions will be visually evaluated, indicators of skewness, kurtosis, and the D'Agostino-Pearson normality test will be used.

In addition to checking the type of distribution of variables, the equality of variances of the studied groups will be assessed using the methods of analysis of variance, in particular the Brown-Forsythe test.

Methods of descriptive analysis will be used depending on the type of distribution of the variable. With a normal distribution, the mean (M) and standard deviation (SD) will be calculated. In case of an nongaussian distribution, the median (Me) and interquartile range will be calculated. Different algorithms of statistical analysis will be applied depending on the type of distribution of variables.

Comparison of the paired and unpaired groups with a normal distribution, in case of the equality of the variances, will be carried out by the methods of analysis of variance ANOVA. Comparison of groups in pairs will be performed using the post-hoc method of posterior multiple comparisons (Tukey test).

Comparison of groups in which variables do not follow the normal distribution will be carried out using the methods of nonparametric analysis of variations: the Kruskal-Wallis test (ANOVA tests) for independent groups and the Friedman test for matched groups. Dunn's multiple comparison test will be used to assess intergroup differences.

Before assessing intergroup differences, the initial samples (1 visit) will be analyzed for identity using ANOVA or nonparametric Kruskal-Wallis tests (depending on the type of data). In case of significant differences in the samples, the search and removal of extremely deviating values (outliers) will be carried out.

Differences will be considered statistically significant if the significance P values are \<0.05.

Eligibility criteria: Inclusion Criteria:

* Age of over 50 years old, inclusive;
* Participants diagnosed with genitourinary menopausal syndrome with severe signs of vulvovaginal atrophy;
* Participants were examined according to the proposed protocol;
* Participants who signed informed consent and fully informed about the purpose of the study.

Exclusion Criteria:

* Tendency to photoallergy including taking photosensitizing drugs (diuretics, antihistamines, antipsychotics);
* Porphyria;
* Active tuberculosis;
* Damage to the vaginal mucosa;
* Urinary tract infections in the acute stage;
* Genital herpes in the acute stage;
* Inflammatory diseases of the vulva and vagina in the acute stage;
* Oncological diseases of the female reproductive system, including history of oncological diseases;
* Precancerous diseases of the cervix, vagina and vulva;
* The use of drugs and other methods of treatment (including laser) that can affect the result, less than 1 month before the start of the study and during the study (Menopausal hormone therapy, the use of topical estriol; Kegel exercises, physiotherapy, the use of pelvic floor muscle trainers).
* Protocol non-compliance of laser exposure sessions;
* Voluntary refusal to participate in the study;
* Violation of recommendations for the management of the period after laser treatment;
* Adverse events that occurred during laser processing and research, and associated with them.
* The occurrence of adverse events or other symptoms that are contraindications to laser procedures, as well as the occurrence of cases described in the exclusion criteria.

Primary outcomes:
measure: Mean Change from Baseline of Vaginal Health Index Score
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
Secondary outcomes:
Other outcomes:
measure: Mean Change from Baseline of "Desire" Score on the Female Sexual Function Index Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Arousal" Score on the Female Sexual Function Index Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Lubrication" Score on the Female Sexual Function Index Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Orgasm" Score on the Female Sexual Function Index Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Satisfaction" Score on the Female Sexual Function Index Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Pain" Score on the Female Sexual Function Index Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Sexual Function in Women with Urinary Incontinence and/or Pelvic Organ Prolapse" Score on Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of "Disease-Specific Quality-of-Life Impact of Vulvovaginal Symptoms in Postmenopausal Women" Score on The Vulvovaginal Symptom Questionnaire
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Compression Time of Vagina
timeFrame: [Time Frame: 1st visit (before any treatment); 2nd visit (first treatment) 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Maximum Pressure at Contraction of Vagina
timeFrame: [Time Frame: 1st visit (before any treatment); 2nd visit (first treatment) 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Average Pressure at Contraction of Vagina
timeFrame: [Time Frame: 1st visit (before any treatment); 2nd visit (first treatment) 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Maturation Index in vaginal smear
timeFrame: [Time Frame: 1st visit (before any treatment); 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Stiffness of Tissues of Vulva
timeFrame: [Time Frame: 1st visit (before any treatment); 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Visual Analogue Scale score
timeFrame: [Time Frame: 1st visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of laser treatment; 1 month after 4th visit and 6 months after 4th visit]
measure: Mean Change from Baseline of Vaginal Smear Microbiologic investigation with Gram staining score.
timeFrame: [Time Frame: 1st visit (before any treatment); 1 month after 4th visit and 6 months after 4th visit]
Locations:
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov"
Study officials:
affiliation: Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov
name: Inna A Apolikhina, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: