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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Catherine A Matthews, MD | Professor or Ob/Gyn and Urology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest Baptist Health | Winston-Salem | North Carolina | 27104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27045260 | Background | 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. | |
| 24080300 |
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| ID | Term |
|---|---|
| D056650 | Vulvodynia |
| ID | Term |
|---|---|
| D014845 | Vulvar Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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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.
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| 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. |
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| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. . | 24 weeks |
| Background |
| 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. |
| 24833921 | Background | 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. |
| 27312009 | Background | 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. |
| 25608269 | Background | 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. |
| 27404032 | Background | 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. |
| 27823733 | Background | 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. |
| 25333211 | Background | 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. |
| 25410301 | Background | 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. |
| 27864031 | Background | 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. |
| 20733439 | Background | 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. |
| 28063914 | Background | 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. |
| 27872745 | Background | 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. |
| 27780177 | Background | 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. |
| 15621359 | Background | 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. |
| 27841834 | Background | Pukall CF, Bergeron S, Brown C, Bachmann G, Wesselmann U; Vulvodynia Collaborative Research Group. Recommendations for Self-Report Outcome Measures in Vulvodynia Clinical Trials. Clin J Pain. 2017 Aug;33(8):756-765. doi: 10.1097/AJP.0000000000000453. |
| 3670870 | Background | Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-197. doi: 10.1016/0304-3959(87)91074-8. |
| 1593914 | Background | Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83. |
| 10782451 | Background | 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. doi: 10.1080/009262300278597. |
| 11556941 | Background | Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x. |
| 22588766 | Background | Smarr KL, Keefer AL. Measures of depression and depressive symptoms: Beck Depression Inventory-II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S454-66. doi: 10.1002/acr.20556. No abstract available. |
| 11690728 | Background | Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9. |
| Background | Schreiber, J., Culpeper, L. Suicidal ideation and behavior in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on June 13, 2017.) |
| 26727408 | Background | Bergeron S, Khalife S, Dupuis MJ, McDuff P. A randomized clinical trial comparing group cognitive-behavioral therapy and a topical steroid for women with dyspareunia. J Consult Clin Psychol. 2016 Mar;84(3):259-68. doi: 10.1037/ccp0000072. Epub 2016 Jan 4. |
| 11275387 | Background | Bergeron S, Binik YM, Khalife S, Pagidas K, Glazer HI, Meana M, Amsel R. A randomized comparison of group cognitive--behavioral therapy, surface electromyographic biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. Pain. 2001 Apr;91(3):297-306. doi: 10.1016/S0304-3959(00)00449-8. |
| 18981315 | Background | Fitzmaurice GM, Ravichandran C. A primer in longitudinal data analysis. Circulation. 2008 Nov 4;118(19):2005-10. doi: 10.1161/CIRCULATIONAHA.107.714618. No abstract available. |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |