Clinical trial NCT05335317: Treatment of Vaginal Atrophy With Low Intensity Nanosecond Neodymium Laser
Official title: Study of the Efficiency and Safety of Low-Intensity Neodymium Laser Radiation With a Nanosecond Pulse Duration for Treatment of the Vaginal Walls Atrophic Changes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Postmenopausal Period
Vaginal Atrophy
Vaginal Prolapse
Keywords: Vaginal Atrophy
Vaginal Prolapse
Neodymium Laser
Laser Treatment
Nanosecond
Laser
Vaginal
Postmenopausal
Lead sponsor: MeLSyTech, Ltd
Sponsor class: INDUSTRY
First posted: 2022-04-19
Enrollment: 120
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The aim of study is characteristic of changes in the vaginal wall after treatment of neodymium laser radiation with a wavelength of 1064 nm. To assess the condition of the vaginal walls before and after laser treatment, the following methods will be used: vaginal health index, perineometry, measurement of the vaginal wall thickness by ultrasound, Doppler sonography of the vaginal walls vessels, optical coherence tomography, biopsy, cytological and immunocytochemical methods. The King's Health Questionnaire will be used to collect feedback on changes in the participants life quality. Total up to 100 participants with and 20 participants without postmenopausal atrophy will be involved in the study. Participants will be divided into three groups: laser treatment (study group), topical hormones treatment (control group 1) and no treatment (control group 2) by 70, 30 and 20 participants in each group respectively. The time intervals between special tests and the tests themselves will be the same for all groups. Thus, a direct comparison between conventional treatment (topical hormones), laser treatment of the vaginal atrophy and normal condition without treatment will be made. The main hypothesis of the study is improvement in condition of the vaginal walls after laser treatment compared with the initial state of not less than thirty percent of participants, and improvement in condition on average compared with the control group.

Detailed description: The principle of participant distribution into groups is the main method of treatment of postmenopausal vaginal atrophy. Total up to 100 participants with and 20 participants without postmenopausal atrophy will be involved in the study. Participants will be divided into three groups: laser treatment (study group), topical hormones treatment (control group 1), and no treatment (control group 2) by 70, 30, and 20 participants in each respectively.

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

* General methods: clinical blood analysis, clinical urine test, vaginal smear for flora, femoflor screen (method is intended for the study of vaginal microbiocenosis), cervical oncocytology test, extended colposcopy, pelvic ultrasound.
* Special methods: filling out the questionnaire (King's Health Questionnaire), Vaginal Health Index, ultrasound for assessing blood vessels (Doppler sonography) and vaginal wall thickness, perineometry, optical coherence tomography (OCT), vaginal smear for immunocytochemical examination and cytology.

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. Three follow-up visits will follow: 1, 3 (mandatory) and 6 (optional) 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. d 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.

The CONTROL 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, when the suppository will be used of 2 times a week for 1.5-2 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 special methods only will be performed during the 5th (1 month after the last procedure), 6th (3 months after the last procedure), and 7th (6 months after the last procedure) visits.

For the control group 1 (hormonal treatment): Studies with special methods only will be performed during the 2nd, 3d, and 4th visits. 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 - 3 months after the 4th, the 7th - 6 months after the 4th.

Thus, a direct comparison between conventional treatment (topical hormones) and laser treatment of the vaginal atrophy will be made during the treatment, as well as on follow-up visits in 1, 3 and 6 months after the end of each type of treatment.

For the control group 2 Vaginal Health Index will be estimated only and OCT investigation with biopsy.

The study will be carried out with the participation of several clinics:

1. Privolzhsky Research Medical University (main scientific coordinator, information for participant recruiting),
2. State-Funded Healthcare Institution of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko" (location of laser equipment, laser treatment and participant consultation, special tests, collection of material for cytological and immunocytochemical analysis, recruiting),
3. Municipal Hospital №35 of the Soviet District of Nizhny Novgorod (cytological and immunocytochemical analysis),
4. State-Funded Healthcare Institution of the Nizhny Novgorod region "Municipal Clinical Hospital №29" (information for participant recruiting, general tests to include participants in the study),
5. LLC "Clinic of modern technologies "SADKO" (recruiting, general tests to include participants in the study, location of laser equipment, laser treatment and participant consultation, special tests, collection of material for cytological and immunocytochemical analysis),
6. Medical Center "Imidzh Lab" (information for participant recruiting, general tests to include participants in the study),
7. LLC "Tonus" (information for participant recruiting, general tests to include participants in the study).

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

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 40-75 years, inclusive;
* Vaginal atrophy or 1st grade vaginal prolapse with atrophy, or lack of vaginal atrophy in case of control group 2;
* All participants have informed consent to conduct a course of procedures according to protocol, carry out follow-up visits, and conduct studies.

Exclusion Criteria:

* Age of under 40 and over 75 years old;
* History of oncological diseases;
* Active tuberculosis;
* Inflammatory diseases of the vulva and vagina including genital herpes in the acute stage;
* Urinary tract infections;
* Damage to the vaginal mucosa;
* Pregnancy;
* Tendency to photoallergy including taking photosensitizing drugs (diuretics, antihistamines, antipsychotics);
* Porphyria;
* Cardiac deficiency of 2-3 degrees;
* Chronic renal disease;
* Participants with greater than 1st grade vaginal prolapse;
* Women after childbirth up to 8 weeks;
* Participants who, according to the doctor, are not able to complete the study;
* 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 appearance of contraindications listed in the Exclusion criteria.

Primary outcomes:
measure: Mean Change from Baseline of Vaginal Health Index Score
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of Periodic Acid Schiff Reaction Percentage in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of Resistive Index by Doppler Sonography
timeFrame: 2nd visit (before any treatment);1 month after 4th visit (after the end of any treatment), 3 months after 4th visit, and 6 months after 4th visit
Secondary outcomes:
Other outcomes:
measure: Mean Change from Baseline of "General Health Perceptions" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Incontinence Impact" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Role Limitations" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Physical Limitations" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Social Limitations" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Personal Relationships" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Emotions" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Sleep / Energy" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Severity Measures" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of "Bladder Problems" Score on the King's Health Questionnaire
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 4th visit (4-6 weeks after 3d visit) - the end of any treatment; 1 month after 4th visit, 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of Pressure at Rest with IEASE Device
timeFrame: 2nd visit (before any treatment);1 month after 4th visit (after the end of any treatment), 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of Maximum Pressure at Contraction with IEASE Device
timeFrame: 2nd visit (before any treatment);1 month after 4th visit (after the end of any treatment), 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of Constant Pressure Contraction Duration with IEASE Device
timeFrame: 2nd visit (before any treatment);1 month after 4th visit (after the end of any treatment), 3 months after 4th visit, and 6 months after 4th visit
measure: Mean Change from Baseline of Basal Cells Percentage in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of Parabasal Cells Percentage in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of Intermediate Cells Percentage in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of Superficial cells Percentage in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of Keratinization Index in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of CK14 (Cytokeratin 14) Percentage in Vaginal Smear
timeFrame: 2nd visit (before any treatment); 3d visit (4-6 weeks after 2nd visit); 1 month after 4th visit (after the end of any treatment), 3 months after 4th visit
measure: Mean Change from Baseline of Vaginal Wall Thickness by Ultrasound Scaled Image
timeFrame: 2nd visit (before any treatment);1 month after 4th visit (after the end of any treatment), 3 months after 4th visit, and 6 months after 4th visit
Locations:
city: Nizhny Novgorod
country: Russian Federation
facility: State-Funded Healthcare Institution of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko"
Study officials:
affiliation: Privolzhsky Research Medical University
name: Liya Z Sirotina
role: PRINCIPAL_INVESTIGATOR
References: