Clinical trial NCT05156489: Ultrasound Evaluation and Vestibular Perception Thresholds Changes in Women Affected by Vestibulodynia (VBD) After One Cycle of Pixel CO2-Alma Fractionated Laser
Official title: An Open-Label, Interventional, Not Controlled Pilot Study to Assess Vestibular Mucosa Thickness by Ultrasound Evaluation and Vestibular Perception Thresholds Changes in Women Affected by Vestibulodynia (VBD) After One Cycle of Pixel CO2-Alma Fractionated Laser
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Vestibulodynia (VBD) From at Least 6 Months
Keywords: Vestibulodynia (VBD)
Fractionated Laser
Vaginal dryness.
Lead sponsor: ASST Fatebenefratelli Sacco
Sponsor class: OTHER
Collaborators: name: Opera CRO, a TIGERMED Group Company
First posted: 2021-12-14
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pilot open not comparative
Primary purpose: TREATMENT

Brief summary: Vestibulodynia (VBD), term revised by Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia in 2015, is a vulvar pain of at least 3 months' duration, without clear identifiable cause and localized at vestibuli.

Women affected by this disease report localized hypersensitivity and pain of the vulvar vestibule to the touch (eg, during sexual intercourse or tampon use). This pattern of responses is suggestive of sensory abnormalities in the form of evoked pain (eg, hyperalgesia or allodynia).

Research biopsy studies have demonstrated increased innervation of the vulvar vestibule and increased subepithelial heparinase activity and cytokines that have been associated with neuroinflammatory processes. In addition, the discomfort inherent in VBD is always associated with pelvic floor muscle overactivity, with the development of myofascial trigger points, resulting in localized or radiating pain and/or severe tenderness.

A rich nerve plexus was identified within the vaginal submucosa, which was only composed of sympathetic and parasympathetic axons, with contributions of smaller sensory fibers. The sensory nerve endings of the vulvar vestibule are dense and shallow, making this region more physiologically sensitive. Several works suggest that a thinner vestibular mucosa is more sensitive to nociception because nerve endings become more superficial, thus altering the transduction of mechanical pressure to facilitate nociception.

The CO2 fractionated laser, has been used to safely and effectively treat symptomatic vaginal atrophy. This tool has also been found to be useful in the treatment of vestibulodynia.

In this open pilot study, 30 female subjects aged more 18 years old at inclusion, having symptoms of VBD from at least 6 months, have given her informed consent and meet all the eligibility criteria, will be enrolled. The subjects will be treated with CO2 Fractionated Laser into vestibule, for 3 sessions at monthly intervals with a follow up of 4 months. Subjects will come to a total of 6 visits over a period of 3 months.

The primary objectives of the study are to evaluate the performance and safety of Pixel CO2-Alma Fractionated Laser in women affected by VBD by the assessment of vestibular mucosa thickness by ultrasound evaluation and vestibular perception thresholds changes at day 84 and 120 and by searching the adverse event during all the study. The secondary objectives are the assessment of VAS for burning/pain, and dyspareunia, evaluation of pain and hypersensitivity to the touch by Swab test, Female Sexual Function Index (FSFI) and by Vulval Pain Functional Questionnaire (VQ) at the visits.


Eligibility criteria: Inclusion Criteria:

* Women affected by Vestibulodynia (VBD) from 6 months.
* Women older than 18 years and not yet in menopausa period (12 consecutive months without a menstrual period).
* Vulval pain from moderate to severe (in a Likert scale between 0 =absent and 10 =severe, scored at least 5 after sexual intercourse with penetration).
* Pain localized at vestibuli during sexual intercourse or in activities with pressure on vestibuli (ie bike, horsing).
* Willingness to provide informed consent
* Willing to have sexual intercourse in the study period

Exclusion Criteria:

* Hypersensitivity or intolerance to laser.
* Clinically significant findings on physical examination.
* Any chronic medical condition or psychologic disorder that per opinion of the Principal Investigator would make the patient ineligible for the study.
* Pelvic floor hypertonicity (from moderate to severe) evaluated at screening by the Investigator and scored on a Likert scale between 0 = hypertonicity absent and 3 =severe hypertonicity.
* Active vaginal or vulvar infections (e.g., herpes, candida, STIs)
* Uterine prolapse beyond the hymen.
* Subject has a history of scarring alteration (ie, keloid formation).
* Unknown past or active history of vaginal bleeding disorders.
* Any condition or behavior indicating to the Investigator that the subject is unlikely to be compliant with study procedures and visits.

Primary outcomes:
measure: Vestibular mucosa thickness measured in µm by B-scan ultrasonography (DermaScan C, Cortex Technology, Denmark)
timeFrame: 120 days
measure: Vestibular perception thresholds measured with values from 1 to 25 by Neurometer CPT (Neurotron, Inc, Baltimore, MD)
timeFrame: 120 days
Secondary outcomes:
measure: Dyspareunia by Visual Analogue Scale
timeFrame: 120 days
measure: Burning/pain by Visual Analogue Scale
timeFrame: 120 days
measure: Pain/hypersensitivity to the touch at Swab test measured by Visual Analogue Scale.
timeFrame: 120 days
measure: Sexual Function by Female Sexual Function Index
timeFrame: 120 days
measure: Vulval pain by Vulval Pain Functional Questionnaire (VQ)
timeFrame: 120 days
measure: Vestibular trophism by the Vestibular Health Score
timeFrame: 120 days
measure: Incidence of Treatment-Emergent Adverse Events/ Adverse Device Events/ Serious Adverse Events/ Serious Adverse Device Events [Safety and Tolerability]
timeFrame: up to 120 days
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Ospedale dei Bambini "Vittore Buzzi"
Study officials:
References:
citation: Bornstein J, Goldstein AT, Stockdale CK, Bergeron S, Pukall C, Zolnoun D, Coady D; consensus vulvar pain terminology committee of the International Society for the Study of Vulvovaginal Disease (ISSVD); International Society for the Study of Women's Sexual Health (ISSWSH); International Pelvic Pain Society (IPPS). 2015 ISSVD, ISSWSH, and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia. J Sex Med. 2016 Apr;13(4):607-12. doi: 10.1016/j.jsxm.2016.02.167. Epub 2016 Mar 25.
citation: Goldstein AT, Pukall CF, Brown C, Bergeron S, Stein A, Kellogg-Spadt S. Vulvodynia: Assessment and Treatment. J Sex Med. 2016 Apr;13(4):572-90. doi: 10.1016/j.jsxm.2016.01.020. Epub 2016 Mar 25.
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citation: Morin M, Binik YM, Bourbonnais D, Khalife S, Ouellet S, Bergeron S. Heightened Pelvic Floor Muscle Tone and Altered Contractility in Women With Provoked Vestibulodynia. J Sex Med. 2017 Apr;14(4):592-600. doi: 10.1016/j.jsxm.2017.02.012.
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citation: Murina F, Barbieri S, Lubrano C, Cetin I. Vestibular Mucosa Thickness Measured by Ultrasound in Patients Affected by Vestibulodynia: A Case-Control Study. Sex Med. 2021 Apr;9(2):100320. doi: 10.1016/j.esxm.2020.100320. Epub 2021 Feb 13.
citation: Salvatore S, Athanasiou S, Candiani M. The use of pulsed CO2 lasers for the treatment of vulvovaginal atrophy. Curr Opin Obstet Gynecol. 2015 Dec;27(6):504-8. doi: 10.1097/GCO.0000000000000230.
citation: Murina F, Karram M, Salvatore S, Felice R. Fractional CO2 Laser Treatment of the Vestibule for Patients with Vestibulodynia and Genitourinary Syndrome of Menopause: A Pilot Study. J Sex Med. 2016 Dec;13(12):1915-1917. doi: 10.1016/j.jsxm.2016.10.006. Epub 2016 Nov 15.