Randomized CO2 vs Sham Laser Treatment of Provoked Vestibulodynia

NCT03390049 | Withdrawn FDA Device

• 1 other identifier: IRB00043442
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Vulvodynia is a debilitating chronic vulvar pain lasting at least 3 months without a clear identifiable cause that is challenging to treat effectively. Vulvodynia is a common pain condition: its prevalence is estimated at 7-8% in women between the ages of 18 and 40. Vulvodynia that is provoked and localized to the vestibule (provoked vestibulodynia \[PVD\]) appears to be the most commonly seen in clinical practice. The current treatment approach for PVD follows a trial-and-error strategy from one intervention to another if symptoms fail to remit. Treatment options include reducing vulvar irritation (e.g., by stopping the use of detergents), topical agents (e.g., lidocaine), oral medications, pelvic floor physical therapy, psychotherapy, locally injectable agents (e.g., botulinum toxin A), and surgery (vestibulectomy). Despite the number of available treatment options, treatment failure is common. Fractional carbon-dioxide (CO2) laser is a technology widely used in dermatology for the treatment of various skin conditions. It has also been found to be an effective and safe treatment modality for symptoms of the genitourinary syndrome of menopause. A recent pilot study explored the use of fractional CO2 laser for the treatment of vestibulodynia in 37 subjects, 67.6% of which reported that their symptoms were "improved" or "very improved" after 3 fractional CO2 laser sessions. In addition, the subjects reported statistically-significant decreases in vulvar pain and dyspareunia scores. Though the results of this pilot study are promising, it was of small sample size and did not control for the placebo effect. In cases of PVD, the placebo effect has been found to have a significant impact on self-reported outcomes. Sham procedures, when performed correctly, can be ethically administered and can significantly reduce study bias. The primary aim of this study, therefore, is to assess the difference in vulvar pain intensity scores, at baseline and at 6, 12, 16, and 24 weeks post-randomization, in women with refractory PVD assigned to fractional CO2 laser vs sham laser. This study will provide information about the efficacy of this treatment modality in women with a challenging clinical condition. Hypothesis: Administration of 3 sessions of fractional carbon-dioxide laser to the vulvar vestibule of women with refractory provoked vestibulodynia will result in a clinically-significant greater reduction in vulvar pain intensity scores than placebo (sham laser).

Conditions

Vestibulodynia

Keywords

SmartXide 2 V 2 LR; MonaLisa Touch; DEKA; Fractional CO2 Laser; Sham Laser; Vulvodynia; PVD; Provoked vestibulodynia

Outcome Measures

Primary Outcomes (1)

• Mean change from baseline in subjects' vulvar pain NRS scores

  The primary outcome will be the mean change from baseline in subjects' vulvar pain NRS scores at 6, 12, 16, and 24 weeks post-randomization. At baseline and at each of these time points, subjects will be asked to rate their vulvar pain in the previous 4 weeks. The question posed to subjects will be worded as follows: "Please indicate, on a scale of 0 to 10, where 0 is no pain at all and 10 is the worst pain you have ever felt, the number that best describes the intensity of your vulvar pain with intercourse, on average, in the past 4 weeks. If intercourse has not been attempted, then indicate the number that best describes the intensity of your vulvar pain with other activities that elicit pain (for example, tampon insertion) in the past 4 weeks." NRS - Numeric Rating Scale - widely used clinically for the assessment of pain. A higher score would represent more pain and a poorer outcome than a lower score.

  24 weeks

Secondary Outcomes (10)

• Mean change from baseline in subjects' scores on pain severity subscale VPAQ

  24 weeks

• Mean change from baseline in subjects' scores on pain severity subscale SF-MPQ

  24 weeks

• Mean change from baseline in subjects' scores on pain descriptors subscale VPAQ

  24 weeks

• Mean change from baseline in subjects' scores on the SF-36

  24 weeks

• Mean change from baseline in subjects' scores on the pain interference subscale of the BPI

  24 weeks

Study Arms (2)

Fractional CO2 Laser Treatment

ACTIVE COMPARATOR

Fractional CO2 laser will be applied to the entire vestibule, anteriorly to the fourchette, and laterally to the labia majora. This takes approximately 5 minutes to complete. A treatment cycle will consist of three laser sessions separated by 6 weeks +/- 1 week. The procedures will take place in the outpatient clinic. EMLA cream will be applied to the introitus for 20 minutes and wiped clean and dried prior to each laser session. Subjects will be advised to avoid intercourse for at least 3 days after each laser session because a mild inflammatory reaction may last up to 48 hours after a laser session. Topical lidocaine 5% ointment may be used for any vulvar discomfort post-procedure.

Device: Fractional CO2 Laser Treatment

Sham Laser Treatment

SHAM COMPARATOR

A treatment cycle will consist of three laser sessions separated by 6 weeks +/- 1 week. The procedures will take place in the outpatient clinic. Subjects assigned to sham laser will undergo the same pre-treatment with EMLA cream and will receive the same post-treatment instructions as the fractional CO2 laser subjects.

Device: Sham Laser Treatment

Interventions

Fractional CO2 Laser Treatment DEVICE

After obtaining a negative urine pregnancy test, each subject assigned to the fractional CO2 laser treatment arm will undergo laser sessions with the fractional microablative CO2 laser system (SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy) using the flat vulvar probe with the following settings: dot power 26 Watts, dwell time 1000 μs, dot spacing 1000 μm, and smart stack parameter from 1 to 3. Stack 1 is used at baseline; stack 3 is used 6 and 12 weeks after.

Also known as: Fractional microablative CO2 laser system

Fractional CO2 Laser Treatment

Sham Laser Treatment DEVICE

After obtaining a negative urine pregnancy test, each subject assigned to the sham laser treatment arm will undergo laser sessions with the fractional microablative CO2 laser system (SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Florence, Italy) using the flat vulvar probe. However, these sham laser sessions will administer no fractional CO2 laser energy. To increase the likelihood that subjects assigned to sham laser remain blinded to treatment arm assignment during the study, MonaLisa Touch will provide a software package with settings that allow for reproduction of the sounds generated during a regular fractional CO2 laser session but using 0 Watts of power.

Also known as: Fractional microablative CO2 laser system

Sham Laser Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 or older
• Meets the 2015 terminology for the diagnosis of PVD, either type 1 (chronic vulvar pain since first attempts at intercourse and/or other penetrative activities) or type 2 (chronic vulvar pain with intercourse and/or other penetrative activities following a period of no vulvar pain)
• Vulvar pain is localized to the vestibule and provoked by vaginal intercourse, other penetrative activities (e.g., tampon insertion, self-stimulation) and/or pressure exerted on the vestibule (e.g., due to tight-fitting clothing, cycling)
• Vestibular pain is elicited with cotton-swab test during screening medical examination
• Subject did not experience significant symptom improvement with prior therapy following a minimum of 2 standard-of-care treatments for PVD

You may not qualify if:

• Currently receiving any type of treatment for PVD, including topical agents (e.g., lidocaine), oral medications (e.g., tricyclic antidepressants, anticonvulsants), pelvic floor physical therapy, psychotherapy, or locally injectable agents (e.g., botulinum toxin A)
• Generalized vulvar pain
• Unprovoked vulvar pain
• History of vestibulectomy
• Any medical, gynecologic, or iatrogenic condition (e.g., vulvar surgery) that could explain the presence of chronic vulvar pain (e.g., genitourinary syndrome of menopause, lichen sclerosus, vaginismus, significant pelvic organ prolapse, pudendal neuralgia)
• Active vulvar and/or vaginal infection that is not due to bacterial vaginosis, Chlamydia, Trichomonads or Candida (if diagnosed with any of these infections, treat and re-evaluate after negative test of cure)
• Active urinary tract infection
• Currently pregnant or breastfeeding
• Recent vaginal delivery (within 3 months post-partum)
• Medical or psychiatric condition not under control
• Scoring of 10 or above on the PHQ-9 and/or scoring 1 or above on the question asking about "thoughts that you would be better off dead, or of hurting yourself in some way"
• History of treatment with fractional CO2 laser to the vulvar vestibule and/or vagina
• History of radiation to vaginal/colorectal tissue, reconstructive pelvic surgery with "mesh kits", impaired wound healing or keloid formation, and/or thromboembolic condition

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27104, United States

Location

Related Publications (26)

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MeSH Terms

Conditions

Vulvodynia

Condition Hierarchy (Ancestors)

Vulvar Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Catherine A Matthews, MD

  Professor or Ob/Gyn and Urology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Each subject will be assigned a study identification number, and demographic and clinical data will be recorded in REDCAP on de-identified data collection forms. The lead research coordinator will maintain the key linking the identification number to each subject in a locked, password-protected site. A random number generator in REDCAP will then randomly assign each subject to either fractional CO2 laser or sham laser. The physician administering the laser sessions will be blinded to treatment arm assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2017
• First Posted: January 4, 2018
• Study Start: August 1, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: June 10, 2019

Record last verified: 2018-02

Locations

US (1)