New Non-Hormonal Treatment by Radiofrequency for Vulvo-Vaginal Atrophy

Study Overview
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Brief Summary
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Vulvo-Vaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) is a common and under-reported condition associated with decreased estrogenization of the vaginal tissue The aim of this study is to evaluate safety and efficacy of  Dynamic Quadripolar Radio-frequency thermal treatment with Vaginal Dynamic Radio-frequency (VDR™) and Radio-frequency Safety System (RSS™) for the treatment of VVA and GSM in postmenopausal women who either present contra-indication for menopause hormone therapy, or are not willing to use Menopause Hormone Therapy (MHT) or have failed to be helped using MHT.

Official Title
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Thermal Treatment of Vulvo-vaginal Atrophy (VVA) Using Novel Low-energy Dynamic Quadripolar Radio-Frequency (DQRF)

Conditions
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Vulvo-vaginal Atrophy, Genitourinary Syndrome of Menopause

Intervention / Treatment
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* Device: Dynamic Quadripolar Radio-Frequency treatment
* Drug: pH-Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women suffering of Vulvo-Vaginal atrophy (VVA), included Breast Cancer survivors defined as having self-identified at least one mild to severe of the following symptoms: Vaginal dryness (none, mild, moderate or severe), Vaginal and/or vulvar irritation/itching (none, mild, moderate or severe), Vaginal pain associated with sexual activity (none, mild, moderate or severe) Postmenopausal women with VVA confirmed by at least one of the following criteria: A proportion of superficial cells ≤ 5% in the vaginal smear using a Maturation Index A vaginal pH > 5 Postmenopausal women between 40 and 75 years of age (non hysterectomized or hysterectomized). Menopause will be assessed either by amenorrhea of > 1 year and / or by Follicle Stimulating Hormone (FSH) > 30 UI/L and estradiol (E2) < 20 pg/ml They must have either a contraindication to hormonal therapies, a failure of previous use of hormonal therapies (either systemic and/or local) or must have refused to take hormonal therapy. Willing to participate in the study and sign an informed consent. Exclusion Criteria: Undiagnosed abnormal genital bleeding. The administration of any investigational drug within 30 days of screening visit. Endometrial hyperplasia at biopsy performed at screening or endometrial cancer. Use of estrogens/progestins products (vaginal, oral, pellet, transdermal....) in the 4 weeks to months (depending on the product used) prior study entry. Presence of severe medical disease or neurological disease or important co-morbidities. Other gynaecological malignancies. Recent vaginal surgery . A clinically relevant prolapse (Pelvic Organ Prolapse-Quantification System (POP-Q) ≤ 2) Current urinary tract or vaginal infection or recent sexually transmitted disease Anticoagulant treatment People with pacemakers and/or other implanted electrodes (Intra-Uterine Device (IUD) and surgical pelvic implants for sterilization are not considered as contraindication) Disabled people unable to communicate

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Group : pH-Cream<br>Control Group will be only treated with a fixed amount (1g) of pH-cream (Cetomacrogol cream) to self-administered with a vaginal applicator for 12 weeks (one dose every three days and if deem necessary, additional doses can be applied and notified in the calendar provided). | Drug: pH-Cream<br>* 1g of Cetomacrogol cream (pH-cream) to self-administered with a vaginal applicator for 12 weeks (one dose every three days)<br>* Other names: Cetomacrogol cream;|
| Experimental: Dynamic Quadripolar Radio-Frequency treatment<br>Experimental Group will be treated with Dynamic Quadripolar Radio-Frequency (DQRF) (with Eva™ Device) for 8 weeks (+ 4 weeks). The Dynamic Quadripolar Radio-frequency sessions will involve -5 sessions (one every 14-21 days), if necessary External treatment (vulvar - will be applied before internal treatment for more comfort) : 10 minutes (5 minutes left side, 5 minutes right side), and Internal treatment (VVA, Vaginal Laxity, Mild-Stress Urinary Incontinence (SUI)): 20 minutes. In parallel, patients can also apply pH-cream (Cetomacrogol cream) (one dose of 1g) if they judge necessary but they are not allowed to use it during the seven days before radiofrequency session. If they use pH-cream, they must notify it in the calendar provided. | Device: Dynamic Quadripolar Radio-Frequency treatment<br>* Novel low-energy Dynamic Quadripolar Radio-frequency thermal treatment through Eva™ Device. Eva™ Device combines both advanced VDR™ technology (Vaginal Dynamic Radiofrequency) and RSS™ (Radiofrequency Safely System) technology.<br>Drug: pH-Cream<br>* 1g of Cetomacrogol cream (pH-cream) to self-administered with a vaginal applicator for 12 weeks (one dose every three days)<br>* Other names: Cetomacrogol cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to week 12 (+4 weeks) of self-assessment of the most bothersome symptom dyspareunia, evaluated by a questionnaire | The severity of dyspareunia recorded as none, mild, moderate or severe (score values of 0, 1, 2 or 3, respectively). Data obtained at baseline and week 12 (+4 weeks). | Up to 12 (+4 weeks) week after beginning of treatment | 
| Change from baseline to week 12 (+4 weeks) of vaginal cell maturation (Maturation Index). | The percentage of parabasal, superficial, intermediate cells will be determined from the vaginal smears collected during the study at baseline and week 12 (+4 weeks). The maturation index is the proportion of these 3 types of cells in each 100 cells counted on a smear. | Up to 12 (+4 weeks) week after beginning of treatment | 
| Change from baseline to week 12 (+4 weeks) of vaginal pH | A pH strip will be applied directly to the lateral wall of the vagina using forceps. The change in color of the pH indicator strip will be compared to the color chart for pH evaluation.Data obtained at baseline and week 12 (+4 weeks) | Up to 12 (+4 weeks) week after beginning of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to week 12 (+4 weeks) of the Vaginal Health Index (VHI) | Evaluation of each of the four following signs of atrophy, which constitute together the Vaginal Health Index (VHI). Vaginal Secretions, Vaginal Epithelial Integrity, Vaginal Epithelial Surface Thickness, Vaginal Color will be evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy and will be analyzed using the score values of 1, 2, 3 and 4, respectively. The visual evaluation of the vagina (petechiae, pallor, friability and dryness or redness in vaginal mucosa) will be assessed using the pictures by the physician blinded to the treatment. Data will be obtained at baseline and week 12 (+4 weeks). | Up to 12 (+4 weeks) week after beginning of treatment | 
| Change from baseline to week 12 (+4 weeks) of the vulvovaginal symptoms | The vulvovaginal symptoms will be evaluated by a 'vulvovaginal symptoms questionnaire in postmenopausal women at baseline and week 12 (+4 weeks). | Up to 12 (+4 weeks) week after beginning of treatment | 
| Change from baseline to week 12 (+4 weeks) in the two groups of the Female Sexual Function Index (FSFI) | The Female Sexual Function Index is measured by a questionnaire evaluating self-reported sexual functioning during the previous month. This includes 19 items grouped within six central domains: desire (items 1 and 2), arousal (items 3 to 6), lubrication (items 7 to 10), orgasm (items 11 to 13), global sexual and relationship satisfaction (items 14 to 16), and pain (items 17 to 19). Each domain was scored on a scale of 0 to 6 with lower scores indicating lower sexual functioning. A domain score of 0 indicated that the women reported no sexual activity. The individual domain scores were then totaled and multiplied by a predetermined factor to weight each domain equally. | Up to 12 (+4 weeks) week after beginning of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vulvo-vaginal atrophy, Dynamic Quadripolar Radio-Frequency, Menopause, Genitourinary syndrome of menopause