VestibulodyniaNCT03390049

Randomized CO2 vs Sham Laser Treatment of Provoked Vestibulodynia

A study testing Fractional CO2 Laser Treatment in people with Vestibulodynia, run by Wake Forest University Health Sciences at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Vestibulodynia
What is being tested?: Fractional CO2 Laser Treatment
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Aug 2018to Nov 2019
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 13Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Wake Forest Baptist Health
Winston-Salem, North Carolina, 27104

Other trials in United States

About this study

Official title: Randomized Controlled Trial of Fractional CO2 Laser vs Sham Laser for Women With Provoked Vestibulodynia Who Have Failed Conservative Management

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
Being tested: Fractional CO2 Laser Treatment, Sham Laser Treatment
Keywords: SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Fractional CO2 Laser, Sham Laser, Vulvodynia, PVD, Provoked vestibulodynia
Medical subject headings: Vulvodynia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fractional CO2 Laser TreatmentDevice
Also called Fractional microablative CO2 laser system
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.
Sham Laser TreatmentDevice
Also called Fractional microablative CO2 laser system
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.

Study groups in NCT03390049
Study group	Role	What they receive
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. Receives: 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. Receives: Device: Sham Laser Treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 24 weeks

Secondary outcomes (10)

Mean change from baseline in subjects' scores on pain severity subscale VPAQ
The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to assess the dimensions of the pain experience in studies of chronic pain. It consists of 6 primary (pain severity, emotional response, cognitive response, and interference with life, sexual function, and self-stimulation/penetration) and 3 supplementary subscales (pain quality, coping skills, and partner factors). The pain severity subscale of the VPAQ consists of 3 pairs of verbal rating scales (VRS) that test both pain intensity and pain affect (i.e., the emotional response generated by the feeling of pain). Each VRS is a 5-point scale with the following options: none=0, mild=1, moderate=2, severe=3, and worst possible=4, with a mean being calculated to produce the overall score for this subscale. The scale is 0-4 with 4 being the worst possible outcomes.
Measured: 24 weeks
Mean change from baseline in subjects' scores on pain severity subscale SF-MPQ
The Short-Form McGill Pain Questionnaire (SF-MPQ), a well-validated measure of both pain affect and pain quality, consists of 15 pain descriptors rated on a 4-point VRS (none=0, mild=1, moderate=2, severe=3) to yield a total score on a scale from 0-60, where a lower score would represent less pain and a better outcome.
Measured: 24 weeks
Mean change from baseline in subjects' scores on pain descriptors subscale VPAQ
The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to assess the dimensions of the pain experience in studies of chronic pain. It consists of 6 primary (pain severity, emotional response, cognitive response, and interference with life, sexual function, and self-stimulation/penetration) and 3 supplementary subscales (pain quality, coping skills, and partner factors). The pain descriptors subscale of the VPAQ tests pain quality (i.e., how the pain is described in terms of sensory descriptors). It consists of 10 adjectives rated on a 5-point VRS (not at all=0, a little=1, somewhat=2, a lot=3, very much=4) to yield a total score from the mean of the adjectives to represent this subscale. The scale is 0-4 with 4 being the worst outcome.
Measured: 24 weeks
Mean change from baseline in subjects' scores on the SF-36
The 36-item Short-Form Health Survey (SF-36) consists of 36 questions assessing physical functioning, role functioning difficulties caused by physical problems, bodily pain, general health, vitality, social functioning, role functioning difficulties caused by emotional problems, and mental health. Scoring the SF-36 is a two-step process. All items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores. Scale scores represent the average for all items in the scale that the respondent answered. High scores are representative of a great health status and better outcomes, while low scores are representative of a poor health status.
Measured: 24 weeks
Mean change from baseline in subjects' scores on the pain interference subscale of the BPI
The pain interference subscale of the Brief Pain Inventory (BPI), also a generic measure, assesses the degree to which a chronic pain condition interferes with 7 general life domains: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The scale goes from 0-10 with 10 being the worst. It assesses pain at its worst, lease, average, and now (current pain).The mean score for the interference of all of the activities for each severity item (worst, least, average, now) is calculated with a higher score (near 10) being a worse outcome.
Measured: 24 weeks
Mean change from baseline in subjects' scores on the life interference subscale of the VPAQ
The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to assess the dimensions of the pain experience in studies of chronic pain. It consists of 6 primary (pain severity, emotional response, cognitive response, and interference with life, sexual function, and self-stimulation/penetration) and 3 supplementary subscales (pain quality, coping skills, and partner factors). The life interference subscale of the VPAQ tests interference of pain with normal life activities. It consists of 11 everyday activities that could be interrupted by pain rated on a 5-point VRS (not at all=0, a little=1, somewhat=2, a lot=3, very much/I avoid because of pain=4) to yield a total score from the mean of the activities to represent this subscale. The scale is 0-4 with 4 being the worst outcome.
Measured: 24 weeks
Mean change from baseline in subjects' scores on the life interference subscale of the FSFI
The Female Sexual Function Index (FSFI), the most-commonly used generic measure of sexual function in women in PVD studies, consists of 6 subscales related to sexual desire (2 Qs scale 1 worst - 5 best), arousal (4Qs 0 worst - 5 best), lubrication (4Qs 0 worst - 5 best), orgasm (3Qs 0 worst - 5 best), satisfaction (3Qs 0 worst - 5 best), and pain (3Qs 0 worst - 5 best). The sexual function interference subscale of the VPAQ assesses the impact of chronic vulvovaginal pain on sexual function. Higher scores indicate higher sexual functioning, with an overall range of 2-36.. A score of 26.55 has been clinically selected as the cut-off for sexual dysfunction, with a score lower than that indicating this problem.
Measured: 24 weeks
Mean change from baseline in subjects' scores on the sexual function interference subscale of the VPAQ
The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to assess the dimensions of the pain experience in studies of chronic pain. It consists of 6 primary (pain severity, emotional response, cognitive response, and interference with life, sexual function, and self-stimulation/penetration) and 3 supplementary subscales (pain quality, coping skills, and partner factors). The sexual function interference subscale of the VPAQ tests interference of pain with sexual activities. It consists of 10 sexual activities that could be interrupted by pain rated on a 5-point VRS (not at all=0, a little=1, somewhat=2, a lot=3, very much/I avoid because of pain=4) to yield a total score from the mean of the activities to represent this subscale. The scale is 0-4 with 4 being the worst outcome.
Measured: 24 weeks
Mean change from baseline in subjects' scores on the sexual function interference subscale of the PHQ-9
The Patient Health Questionnaire-9 (PHQ-9) is 1 of 3 scales recommended by the National Institute for Health and Clinical Excellence for use in primary care to measure baseline depression severity and responsiveness to treatment. The scale goes from 0-27 with 0-4 indicating minimal depression with treatment unlikely to be necessary, 5-9 indicating mild depression and 10-14 indicating moderate depression with physicians using their clinical judgement for treatment (score 5-14) based on individual patient, 15-19 indicating moderately severe depression and 20-27 indicating severe depression warrant treatment for the depression (score >14). A higher score would represent a poorer outcome for this scale.
Measured: 24 weeks
Comparison of percentages of subjects in each treatment arm endorsing improvement in symptoms on the PGIC scale
The Patient Global Impression of Change (PGIC) is a 7-point scale that rates the level of satisfaction with treatment (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse). 10 point scale with 0=much better, 5=no change, and 10=much worse. Scores less than 5 would represent good outcomes. .
Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2018Nov 2019

First posted4 Jan 2018
Study startAug 2018 (estimated)
Primary completionNov 2019 (estimated)
Study completionNov 2019 (estimated)

Why it stopped: No funding

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (26)Papers the sponsor has linked to this study.
Other trials for VestibulodyniaStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03390049
Sponsor's protocol ID: IRB00043442
Status last verified: Feb 2018
First submitted: 26 Dec 2017
Last updated: 10 Jun 2019
Results posted: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: Undecided

Publications

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.
PubMed 27045260
Harlow BL, Kunitz CG, Nguyen RH, Rydell SA, Turner RM, MacLehose RF. Prevalence of symptoms consistent with a diagnosis of vulvodynia: population-based estimates from 2 geographic regions. Am J Obstet Gynecol. 2014 Jan;210(1):40.e1-8. doi: 10.1016/j.ajog.2013.09.033. Epub 2013 Sep 28.
PubMed 24080300
Sadownik LA. Etiology, diagnosis, and clinical management of vulvodynia. Int J Womens Health. 2014 May 2;6:437-49. doi: 10.2147/IJWH.S37660. eCollection 2014.
PubMed 24833921
Falsetta ML, Foster DC, Bonham AD, Phipps RP. A review of the available clinical therapies for vulvodynia management and new data implicating proinflammatory mediators in pain elicitation. BJOG. 2017 Jan;124(2):210-218. doi: 10.1111/1471-0528.14157. Epub 2016 Jun 17.
PubMed 27312009
Salvatore S, Leone Roberti Maggiore U, Athanasiou S, Origoni M, Candiani M, Calligaro A, Zerbinati N. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015 Aug;22(8):845-9. doi: 10.1097/GME.0000000000000401.
PubMed 25608269
Sokol ER, Karram MM. An assessment of the safety and efficacy of a fractional CO2 laser system for the treatment of vulvovaginal atrophy. Menopause. 2016 Oct;23(10):1102-7. doi: 10.1097/GME.0000000000000700.
PubMed 27404032
Pitsouni E, Grigoriadis T, Tsiveleka A, Zacharakis D, Salvatore S, Athanasiou S. Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: An observational study. Maturitas. 2016 Dec;94:131-136. doi: 10.1016/j.maturitas.2016.09.012. Epub 2016 Sep 16.
PubMed 27823733
Salvatore S, Nappi RE, Parma M, Chionna R, Lagona F, Zerbinati N, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. Sexual function after fractional microablative CO(2) laser in women with vulvovaginal atrophy. Climacteric. 2015 Apr;18(2):219-25. doi: 10.3109/13697137.2014.975197. Epub 2014 Dec 16.
PubMed 25333211
Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligaro A. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015 Jan;30(1):429-36. doi: 10.1007/s10103-014-1677-2. Epub 2014 Nov 20.
PubMed 25410301
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.
PubMed 27864031
Foster DC, Kotok MB, Huang LS, Watts A, Oakes D, Howard FM, Poleshuck EL, Stodgell CJ, Dworkin RH. Oral desipramine and topical lidocaine for vulvodynia: a randomized controlled trial. Obstet Gynecol. 2010 Sep;116(3):583-593. doi: 10.1097/AOG.0b013e3181e9e0ab.
PubMed 20733439
Gu AP, Gu CN, Ahmed AT, Murad MH, Wang Z, Kallmes DF, Brinjikji W. Sham surgical procedures for pain intervention result in significant improvements in pain: systematic review and meta-analysis. J Clin Epidemiol. 2017 Mar;83:18-23. doi: 10.1016/j.jclinepi.2016.12.010. Epub 2017 Jan 4.
PubMed 28063914
Ciccozzi M, Menga R, Ricci G, Vitali MA, Angeletti S, Sirignano A, Tambone V. Critical review of sham surgery clinical trials: Confounding factors analysis. Ann Med Surg (Lond). 2016 Oct 29;12:21-26. doi: 10.1016/j.amsu.2016.10.007. eCollection 2016 Dec.
PubMed 27872745
Dargie E, Holden RR, Pukall CF. The Vulvar Pain Assessment Questionnaire inventory. Pain. 2016 Dec;157(12):2672-2686. doi: 10.1097/j.pain.0000000000000682.
PubMed 27780177
Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1-2):9-19. doi: 10.1016/j.pain.2004.09.012. No abstract available.
PubMed 15621359

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Vestibulodynia trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Controlled Trial of Fractional CO2 Laser vs Sham Laser for Women With Provoked Vestibulodynia Who Have Failed Conservative Management
ClinicalTrials.gov ID: NCT03390049
Acronym / sponsor ID: IRB00043442
Conditions: Vestibulodynia
Keywords: SmartXide 2 V 2 LR, MonaLisa Touch, DEKA, Fractional CO2 Laser, Sham Laser, Vulvodynia, PVD, Provoked vestibulodynia
Study type: Interventional
Recruitment status: WithdrawnReason stopped: No funding
Enrolment: 0 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Study start: Aug 2018 (estimated)
Primary completion: Nov 2019 (estimated)
Study completion: Nov 2019 (estimated)
First posted: 4 Jan 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Fractional CO2 Laser Treatment	Active comparator	Device: Fractional CO2 Laser TreatmentFractional 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.
Sham Laser Treatment	Sham comparator	Device: Sham Laser TreatmentA 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (13 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Fractional CO2 Laser TreatmentAlso: Fractional microablative CO2 laser systemAfter 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.	Device	Fractional CO2 Laser Treatment
Sham Laser TreatmentAlso: Fractional microablative CO2 laser systemAfter 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.	Device	Sham Laser Treatment

Primary outcome

Mean change from baseline in subjects' vulvar pain NRS scores
Time frame: 24 weeks
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.

10 secondary outcomes

Mean change from baseline in subjects' scores on pain severity subscale VPAQ
Time frame: 24 weeks
Mean change from baseline in subjects' scores on pain severity subscale SF-MPQ
Time frame: 24 weeks
Mean change from baseline in subjects' scores on pain descriptors subscale VPAQ
Time frame: 24 weeks
Mean change from baseline in subjects' scores on the SF-36
Time frame: 24 weeks
Mean change from baseline in subjects' scores on the pain interference subscale of the BPI
Time frame: 24 weeks
Mean change from baseline in subjects' scores on the life interference subscale of the VPAQ
Time frame: 24 weeks
Mean change from baseline in subjects' scores on the life interference subscale of the FSFI
Time frame: 24 weeks
Mean change from baseline in subjects' scores on the sexual function interference subscale of the VPAQ
Time frame: 24 weeks
Mean change from baseline in subjects' scores on the sexual function interference subscale of the PHQ-9
Time frame: 24 weeks
Comparison of percentages of subjects in each treatment arm endorsing improvement in symptoms on the PGIC scale
Time frame: 24 weeks

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2019.
Background: PubMed 27045260Bornstein 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.
Background: PubMed 24080300Harlow BL, Kunitz CG, Nguyen RH, Rydell SA, Turner RM, MacLehose RF. Prevalence of symptoms consistent with a diagnosis of vulvodynia: population-based estimates from 2 geographic regions. Am J Obstet Gynecol. 2014 Jan;210(1):40.e1-8. doi: 10.1016/j.ajog.2013.09.033. Epub 2013 Sep 28.
Background: PubMed 24833921Sadownik LA. Etiology, diagnosis, and clinical management of vulvodynia. Int J Womens Health. 2014 May 2;6:437-49. doi: 10.2147/IJWH.S37660. eCollection 2014.
Background: PubMed 27312009Falsetta ML, Foster DC, Bonham AD, Phipps RP. A review of the available clinical therapies for vulvodynia management and new data implicating proinflammatory mediators in pain elicitation. BJOG. 2017 Jan;124(2):210-218. doi: 10.1111/1471-0528.14157. Epub 2016 Jun 17.
Background: PubMed 25608269Salvatore S, Leone Roberti Maggiore U, Athanasiou S, Origoni M, Candiani M, Calligaro A, Zerbinati N. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015 Aug;22(8):845-9. doi: 10.1097/GME.0000000000000401.
Background: PubMed 27404032Sokol ER, Karram MM. An assessment of the safety and efficacy of a fractional CO2 laser system for the treatment of vulvovaginal atrophy. Menopause. 2016 Oct;23(10):1102-7. doi: 10.1097/GME.0000000000000700.
Background: PubMed 27823733Pitsouni E, Grigoriadis T, Tsiveleka A, Zacharakis D, Salvatore S, Athanasiou S. Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: An observational study. Maturitas. 2016 Dec;94:131-136. doi: 10.1016/j.maturitas.2016.09.012. Epub 2016 Sep 16.
Background: PubMed 25333211Salvatore S, Nappi RE, Parma M, Chionna R, Lagona F, Zerbinati N, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. Sexual function after fractional microablative CO(2) laser in women with vulvovaginal atrophy. Climacteric. 2015 Apr;18(2):219-25. doi: 10.3109/13697137.2014.975197. Epub 2014 Dec 16.
Background: PubMed 25410301Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligaro A. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015 Jan;30(1):429-36. doi: 10.1007/s10103-014-1677-2. Epub 2014 Nov 20.
Background: PubMed 27864031Murina 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.
Background: PubMed 20733439Foster DC, Kotok MB, Huang LS, Watts A, Oakes D, Howard FM, Poleshuck EL, Stodgell CJ, Dworkin RH. Oral desipramine and topical lidocaine for vulvodynia: a randomized controlled trial. Obstet Gynecol. 2010 Sep;116(3):583-593. doi: 10.1097/AOG.0b013e3181e9e0ab.
Background: PubMed 28063914Gu AP, Gu CN, Ahmed AT, Murad MH, Wang Z, Kallmes DF, Brinjikji W. Sham surgical procedures for pain intervention result in significant improvements in pain: systematic review and meta-analysis. J Clin Epidemiol. 2017 Mar;83:18-23. doi: 10.1016/j.jclinepi.2016.12.010. Epub 2017 Jan 4.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Catherine A Matthews, MD principal investigator

Professor or Ob/Gyn and Urology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Fractional CO2 Laser Treatment in people with Vestibulodynia, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change from baseline in subjects' vulvar pain NRS scores (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03390049, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019.