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

Genitourinary Syndrome of Menopause Clinical Trial

— ViViA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03857893
• Other study ID #: B076201938646
• Status: Terminated
• Phase: N/A
• Start date: March 1, 2019
• Est. completion date: December 8, 2021

Study information

• Verified date: March 2022
• Source: Centre Hospitalier Universitaire Saint Pierre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 53
• Est. completion date: December 8, 2021
• Est. primary completion date: December 8, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 75 Years

Eligibility

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:

1. Vaginal dryness (none, mild, moderate or severe),

2. Vaginal and/or vulvar irritation/itching (none, mild, moderate or severe),

3. Vaginal pain associated with sexual activity (none, mild, moderate or severe)

• Postmenopausal women with VVA confirmed by at least one of the following criteria:

1. A proportion of superficial cells = 5% in the vaginal smear using a "Maturation Index"

2. 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

Related Conditions & MeSH terms

• Atrophy
• Genitourinary Syndrome of Menopause
• Vulvo-vaginal Atrophy

Intervention

Device:
• Dynamic Quadripolar Radio-Frequency treatment
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.

Drug:
• pH-Cream
1g of Cetomacrogol cream (pH-cream) to self-administered with a vaginal applicator for 12 weeks (one dose every three days)

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels
Belgium	CHU Saint-Pierre	Brussels
Belgium	Hôpital Erasme	Brussels
Belgium	Hôpitaux Iris Sud	Brussels
Belgium	Jules Institute Bordet	Brussels

Sponsors (6)

Lead Sponsor	Collaborator
Serge Rozenberg	Centre Hospitalier Universitaire Brugmann, Erasme University Hospital, Hôpitaux IRIS Sud, Jules Bordet Institute, NOVAVISION GROUP S.P.A

Country where clinical trial is conducted

Belgium, 

References & Publications (16)

Ameye L, Antoine C, Paesmans M, de Azambuja E, Rozenberg S. Menopausal hormone therapy use in 17 European countries during the last decade. Maturitas. 2014 Nov;79(3):287-91. doi: 10.1016/j.maturitas.2014.07.002. Epub 2014 Aug 4. Erratum in: Maturitas. 2015 May;81(1):237-8. — View Citation

Antoine C, Liebens F, Carly B, Pastijn A, Rozenberg S. Safety of alternative treatments for menopausal symptoms after breast cancer: a qualitative systematic review. Climacteric. 2007 Feb;10(1):23-6. Review. — View Citation

Antoine C, Vandromme J, Fastrez M, Carly B, Liebens F, Rozenberg S. A survey among breast cancer survivors: treatment of the climacteric after breast cancer. Climacteric. 2008 Aug;11(4):322-8. doi: 10.1080/13697130802244422. — View Citation

Baumgart J, Nilsson K, Evers AS, Kallak TK, Poromaa IS. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause. 2013 Feb;20(2):162-8. doi: 10.1097/gme.0b013e31826560da. — View Citation

Bouchard C, Labrie F, Derogatis L, Girard G, Ayotte N, Gallagher J, Cusan L, Archer DF, Portman D, Lavoie L, Beauregard A, Côté I, Martel C, Vaillancourt M, Balser J, Moyneur E; VVA Prasterone Group. Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study. Horm Mol Biol Clin Investig. 2016 Mar;25(3):181-90. doi: 10.1515/hmbci-2015-0044. — View Citation

Erekson EA, Yip SO, Wedderburn TS, Martin DK, Li FY, Choi JN, Kenton KS, Fried TR. The Vulvovaginal Symptoms Questionnaire: a questionnaire for measuring vulvovaginal symptoms in postmenopausal women. Menopause. 2013 Sep;20(9):973-9. doi: 10.1097/GME.0b013e318282600b. — View Citation

Goldstein SR, Bachmann GA, Koninckx PR, Lin VH, Portman DJ, Ylikorkala O; Ospemifene Study Group. Ospemifene 12-month safety and efficacy in postmenopausal women with vulvar and vaginal atrophy. Climacteric. 2014 Apr;17(2):173-82. doi: 10.3109/13697137.2013.834493. Epub 2013 Nov 23. — View Citation

Hutchinson-Colas J, Segal S. Genitourinary syndrome of menopause and the use of laser therapy. Maturitas. 2015 Dec;82(4):342-5. doi: 10.1016/j.maturitas.2015.08.001. Epub 2015 Aug 12. Review. — View Citation

Kendall A, Dowsett M, Folkerd E, Smith I. Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol. 2006 Apr;17(4):584-7. Epub 2006 Jan 27. — View Citation

Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women's VIews of Treatment Options for Menopausal Vaginal ChangEs) survey. J Sex Med. 2013 Jul;10(7):1790-9. doi: 10.1111/jsm.12190. Epub 2013 May 16. — View Citation

Melisko ME, Goldman ME, Hwang J, De Luca A, Fang S, Esserman LJ, Chien AJ, Park JW, Rugo HS. Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2017 Mar 1;3(3):313-319. doi: 10.1001/jamaoncol.2016.3904. Erratum in: JAMA Oncol. 2020 Sep 1;6(9):1473. — View Citation

Nappi RE, Kokot-Kierepa M. Women's voices in the menopause: results from an international survey on vaginal atrophy. Maturitas. 2010 Nov;67(3):233-8. doi: 10.1016/j.maturitas.2010.08.001. Epub 2010 Sep 9. — View Citation

Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, D'Agostino R Jr. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. — View Citation

Rozenberg S, Pornel B, Koninckx PR, Palacios S, Christiansen C. Endometrium protection and acceptability of nasally administered continuously combined hormone therapy: a multicentre, multinational, double-blind trial in post-menopausal women evaluating three regimens of 17beta-estradiol and norethisterone when compared with an orally administered 17beta-estradiol norethisterone regimen. Hum Reprod. 2009 Jul;24(7):1739-47. doi: 10.1093/humrep/dep067. Epub 2009 Apr 7. — View Citation

Rozenberg S, Vandromme J, Antoine C. Postmenopausal hormone therapy: risks and benefits. Nat Rev Endocrinol. 2013 Apr;9(4):216-27. doi: 10.1038/nrendo.2013.17. Epub 2013 Feb 19. Review. — View Citation

Vicariotto F, DE Seta F, Faoro V, Raichi M. Dynamic quadripolar radiofrequency treatment of vaginal laxity/menopausal vulvo-vaginal atrophy: 12-month efficacy and safety. Minerva Ginecol. 2017 Aug;69(4):342-349. doi: 10.23736/S0026-4784.17.04072-2. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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