EPMLARF-arm1: LASER and Radiofrequency and Genitourinary Syndrome of Menopause

Sponsor

Federal University of São Paulo (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04045379

Collaborator

Fundação de Amparo à Pesquisa do Estado de São Paulo (Other)

195

Enrollment

Location

Arms

47.9

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized controlled trial to evaluate the use of LASER, Micro Ablative radiofrequency and topic strogen to treat symptoms of vulvovaginal atrophy of post menopause.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Atrophic Vaginitis Postmenopausal Symptoms Genitourinary Symptoms	Procedure: LASER Procedure: Microablative Radiofrequency Drug: Estriol	N/A

Detailed Description

Post menopause women with moderate or severe signs or symptoms of vulvovaginal atrophy will be eligible for the study.

The patients will be randomized to receive one of the three intravaginal therapies: LASER, Micro Ablative radiofrequency or Estriol. The applications will occur in the interval of 30 days for 3 times, for LASER and Radiofrequency groups. For the estriol group, the application will be done by the patient, daily for 2 weeks and them twice a week for 3 months, and each 30 days, the patients will have an appointment when will be checked the weight of the estriol tube, to verify the correct use.

The follow-up visits will occur 30, 90, 180 and 360 days after the conclusion of the third month of treatment.

Will be evaluated: vulvar and vaginal histology before and after the use of LASER, radiofrequency or estriol; microbiota and vaginal pH before and after the use of LASER, radiofrequency or estriol; extracellular matrix and metalloproteinases in the remodeling of vulvovaginal collagen induced by estrogen, LASER and radiofrequency; quality of life, sexual dysfunctions and complaints before and after the use of LASER, radiofrequency or hormones; metabolomics and vaginal microbiome.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

195 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The patient will be randomized in block to receive one of the three intravaginal therapies: LASER, Radiofrequency and topic estriolThe patient will be randomized in block to receive one of the three intravaginal therapies: LASER, Radiofrequency and topic estriol

Masking:

Single (Outcomes Assessor)

Masking Description:

the outcomes assessor will not know which therapy was used by the patient

Primary Purpose:

Treatment

Official Title:

LASER and Radiofrequency as Alternative Treatments for Genitourinary Syndrome of Menopause

Anticipated Study Start Date :

Aug 5, 2019

Anticipated Primary Completion Date :

Aug 1, 2021

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: LASER The patients will receive 3 consecutive applications of intravaginal and vulvar CO2 (carbon dioxide)LASER, according to the manufacturer protocol for vaginal atrophy. The applications will be separated by the interval of 30 days	Procedure: LASER Use of the SmartXide Touch V²LR, Co2 Laser System to perform ambulatory intravaginal and vulvar application of LASER, to postmenopausal genitourinary syndrome. The patient will be in gynecological position, after remove of vaginal secretion, with gauze and under topic anesthesia, the LASER will be applied, according to the protocol of the manufactured. Other Names: Fractional Co2 (carbon dioxide)Laser MonaLisa Touch® treatment SmartXide Touch V²LR® Deka
Active Comparator: Micro Ablative Radiofrequency The patients will receive 3 consecutive applications of intravaginal and vulvar MIcro ablative radiofrequency, according to the manufacturer protocol for vaginal atrophy. The applications will be separated by the interval of 30 days	Procedure: Microablative Radiofrequency Use of Linly™ equipment to perform ambulatory intravaginal and vulvar application of fractionated microablative radiofrequency, to postmenopausal genitourinary syndrome. The patient will be in gynecological position, after remove of vaginal secretion, with gauze and under topic anesthesia, the radiofrequency will be applied, according to the protocol of the manufactured. Other Names: FRAAX Linly™ Loktal Medical Electronics
Active Comparator: Estriol The patient will use intravaginal estriol, daily for 2 weeks and them twice a week for 3 months . Each 30 days, the patients will have an appointment when will be checked the weight of the estriol tube to verify the correct use.	Drug: Estriol The patient will perform self application of this vaginal estriol daily for 2 weeks and after that the applications will occur twice a week. Other Names: Estriol 01mg/ml

Arm

Intervention/Treatment

Active Comparator: LASER

The patients will receive 3 consecutive applications of intravaginal and vulvar CO2 (carbon dioxide)LASER, according to the manufacturer protocol for vaginal atrophy. The applications will be separated by the interval of 30 days

Procedure: LASER

Use of the SmartXide Touch V²LR, Co2 Laser System to perform ambulatory intravaginal and vulvar application of LASER, to postmenopausal genitourinary syndrome. The patient will be in gynecological position, after remove of vaginal secretion, with gauze and under topic anesthesia, the LASER will be applied, according to the protocol of the manufactured.

Other Names:

Fractional Co2 (carbon dioxide)Laser

MonaLisa Touch® treatment

SmartXide Touch V²LR® Deka

Active Comparator: Micro Ablative Radiofrequency

The patients will receive 3 consecutive applications of intravaginal and vulvar MIcro ablative radiofrequency, according to the manufacturer protocol for vaginal atrophy. The applications will be separated by the interval of 30 days

Procedure: Microablative Radiofrequency

Use of Linly™ equipment to perform ambulatory intravaginal and vulvar application of fractionated microablative radiofrequency, to postmenopausal genitourinary syndrome. The patient will be in gynecological position, after remove of vaginal secretion, with gauze and under topic anesthesia, the radiofrequency will be applied, according to the protocol of the manufactured.

Other Names:

FRAAX

Linly™ Loktal Medical Electronics

Active Comparator: Estriol

The patient will use intravaginal estriol, daily for 2 weeks and them twice a week for 3 months . Each 30 days, the patients will have an appointment when will be checked the weight of the estriol tube to verify the correct use.

Drug: Estriol

The patient will perform self application of this vaginal estriol daily for 2 weeks and after that the applications will occur twice a week.

Other Names:

Estriol 01mg/ml

Outcome Measures

Primary Outcome Measures

Clinical Improvement of signs and symptoms postmenopausal genitourinary syndrome with intravaginal LASER, Microablative Radiofrequency, and topic estriol [The evaluation will be done 180 days after treatment]
Will be applied a Visual Analogic Scale (0-10) to access the improvement of genitourinary signs and symptoms, the results of the three groups will be compared
Satisfaction of postmenopausal women with genitourinary syndrome with the treatment by intravaginal LASER, Micro ablative Radiofrequency, and topic estriol [The evaluation will be done 180 days after treatment]
Will be applied a LIKERT Satisfaction Scale (1-5) to access the satisfaction with the treatment, the results of the three groups will be compared

Secondary Outcome Measures

Evaluation of Microbiota before and after the use of intravaginal LASER, Micro Ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment 30, 90 , 180 and 360 days after treatment]
The vaginal flora will be evaluated by vaginal smear. The results of the three groups will be compared
Evaluation of vaginal pH before and after the use of intravaginal LASER, Micro ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment and 30, 90, 180 and 360 days after treatment]
The vaginal pH will be verified by the use of pH tape's .The results of the three groups will be compared
Histologic evaluation of vagina and vulva before and after the use of intravaginal and vulvar LASER, Micro Ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment and 30 days after treatment]
Thickness of epithelium (mm and number of layers), and evaluation of expression of Ki-67 and VEGF (vascular endothelial growth factor) will be done on vaginal and vulvar biopsies.The results of the three groups will be compared
Evaluation of impact in Quality of life after treatment with intravaginal and vulvar LASER, Micro Ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment and 30 days after treatment]
The IQol (incontinence quality of life questionnaire, validated to portuguese language - score 0-100) will be used to evaluate quality of life .The results of the three groups will be compared
Evaluation of impact in Sexual function after treatment with intravaginal and vulvar LASER, Micro Ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment and 30 days after treatment]
The FSF-I(Female Sexual Function Index , validated to portuguese language- score range from 2 - 36) will be used to evaluate sexual function . The results of the three groups will be compared
Evaluation of extracellular matrix before and after the use of intravaginal and vulvar LASER, Micro Ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment and 30 days after treatment]
Evaluation of the composition and concentration of the glycosaminoglycans of extracellular matrix in the vaginal and vulvar biopsies by specific markers. The results of the three groups will be compared
Evaluation of matrix metalloproteinases(MMP) in remodeling of vulvovaginal collagen induced by intravaginal and vulvar LASER, Micro Ablative radiofrequency or topic estriol. [The evaluation will occur pre treatment and 30 days after treatment]
Evaluation of the tissue distribution of the MMP-1, MMP-2, MMP-3, MMP-7, MMP-9 metalloproteinases of collagen I, II, IV and elastin proteins by specific markers on vaginal and vulvar biopsies. The results of the three groups will be compared
Evaluation of visual aspect of vulva after the use of intravaginal and vulvar LASER, Micro Ablative radiofrequency or topic estriol. [The pictures will be taken before and 30 days and 180 days after treatment.]
Pictures of vulva will be taken before and after treatment. The images will be evaluated by a blind gynecologist and dermatologist regarding the type of treatment and the chronological order of the photos, which will classify the images as: better; equal or worse, in relation to tropism and number of vulvar skin grooves, The results of the three groups will be compared

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women between 2 and 5 years after menopause, without hormone therapy for at least 2 years
To present, at least moderate, or severe intensity (score 4 or more of visual analog scale ( 0-10)) of one of the signs or symptoms of of vulvovaginal atrophy:

Burning
Discomfort
Dryness
Cracks
Pruritus
Lack of vaginal lubrication
Penetration dyspareunia that began at the menopausal or postmenopausal transition
Decreased vaginal epithelium turgor and trophism
Deletion of mucous and skin folds.

The Exclusion criteria will be:

Active genital infection, active infection of HPV (human papillomavirus) or Herpes, users of medications with estrogenic effect (digoxin, tamoxifen and other chemicals)
Postmenopausal genital bleeding, uncontrolled diabetes, use of multivitamins with zinc, use of copper or hormonal IUDs (intrauterine device) at the time of inclusion, presence of genitourinary or rectovaginal fistulas.