Clinical trial NCT04613713: Somatocognitive Therapy in Treatment of Provoked (Localized) Vestibulodynia - Randomized Clinical Trial (ProLoVe Study)
Official title: Effectiveness and Cost-utility of Somatocognitive Therapy Versus Treatment as Usual for Provoked (Localized) Vestibulodynia - a Randomized Clinical Trial (ProLoVe Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vulvodynia
Vestibulodynia
Keywords: Provoked vestibulodynia
Dyspareunia
Somatocognitive therapy
Physiotherapy
Randomised clinical trial
Women's health
Sexual dysfunction
Pain management
Lead sponsor: Oslo Metropolitan University
Sponsor class: OTHER
First posted: 2020-11-03
Enrollment: 128
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel group randomized clinical trial
Primary purpose: TREATMENT

Brief summary: This is a two-arm randomized clinical trial assessing effectiveness of somatocognitive therapy versus treatment as usual for provoked vestibulodynia (PVD). PVD is a common, but under-treated persistent pain condition, mostly affecting young women in their late teens and early 20s. It is the most frequent cause of pain during sexual intercourse affecting around 10% of women in the general population. There are no generally accepted evidence-based guidelines for the medical management of PVD. The most commonly used treatments are topical (85%), physiotherapy (52%), and oral medications (45%). High quality randomized clinical trials testing effectiveness of various therapy approaches are urgently needed.

Somatocognitive therapy SCT is a multi-modal physiotherapy approach developed for alleviating musculoskeletal persistent pain conditions. SCT has been previously evaluated in the treatment of women with chronic pelvic pain.

In the current study, 128 women with PVD will be randomized into SCT and treatment as usual (TAU) group. Participants will be assessed at baseline, after 6 months and after 12 months. The main outcome will be changes in female sexual function index scored at 12 months follow up. Secondary outcomes include pain intensity as assessed by a tampon test as well as a number of questionnaires recording different aspects of emotional and cognitive functioning. In addition cost-effectiveness analysis of SCT versus TAU will be performed.

Participants in the SCT group will receive up to 15 therapy sessions and will additionally be offered one booster session at 6 months after treatment ending. TAU group will follow treatment options of their own choice based on recommendations from the Vulva clinic at Oslo University Hospital, a center that is specialized in treating women with vulvar pain conditions.

Detailed description: Objectives:

The main objectives of the ProLoVe study are:

1. To assess clinical effectiveness of somatocognitive therapy (SCT) versus treatment as usual (TAU) in provoked vestibulodynia (PVD).
2. To identify prognostic factors associated with treatment outcome
3. To assess cost-effectiveness and cost-utility of SCT vs TAU.

Study design:

The study is a two-arm, single center randomized clinical trial with a 1:1 allocation ratio, recruiting patients with PVD diagnosis. The participants will be randomized to either somatocognitive therapy (SCT) or treatment as usual (TAU) group after baseline assessment. Randomization will be stratified by type of PVD (primary or secondary), since primary PVD is considered to be more treatment resistant.

Recruitment procedure:

Participants' eligibility will be evaluated by the medical specialist in gynecology or dermatology. During medical consultation an eligible patient will be verbally informed about the study and receive an information leaflet about the project. Number of eligible patients informed about the study, will be registered. Interested women will contact the primary investigator who will set up a meeting. Detailed information about the trial, the assessment instruments and existing treatment options will be provided. Women willing to pursue study participation will sign an informed consent.

Randomization and blinding:

An administrative coordinator, not directly involved in the study, will be responsible for randomization of the participants using a computer random number generator, and will be responsible for the secure storage of randomization results. The participants will be randomized to either somatocognitive physiotherapy (SCT) or treatment as usual group (TAU) at 1:1 allocation rate. Randomization will be stratified by severity (primary/secondary PVD). Blinding of the participants regarding group belonging is not possible.

Data collection:

All quantitative instruments will be distributed as electronic forms (nettskjema.no) and directly transferred to the Service for Sensitive Data (TSD). Choice and implementation of assessment instruments is based on the Recommendations for the study of the vulvar pain in women, part I: review of assessment tools (Rosen et al. 2020), feedback from participants from the feasibility study and discussions with user representative (former PVD patient). Three assessment time points are planned: baseline, 6 months follow up, and 12 months follow up.

Sample size assessment:

Power analysis suggests that 128 participants split equally between two study arms will be enough to reveal the between group difference in total FSFI score changes, from baseline to 12 months follow-up, of at least 3 points (SD = 6.0) as statistically significant, using α = 0.05 and 1-β = 0.8. In a feasibility study (n=10) an average of 6 points improvement on FSFI in course of 8 months in patients treated with SCT was observed.

Data analysis:

Objective 1: To assess clinical effectiveness of somatocognitive therapy (SCT) versus treatment as usual (TAU) in provoked vestibulodynia (PVD).

Hypothesis 1: In treatment of PVD, the effectiveness of somatocognitive therapy is not significantly different from treatment as usual as evaluated by changes in FSFI total score from baseline to 12 months follow-up

Independently, a senior statistician and PhD student blinded to treatment group will perform intention to treat analyses of the treatment effect on the primary outcome by using linear mixed model for repeated measures.

Subgroup analysis (objective 1) Some of the women with PVD do not engage in penetrative sex and thus score 0 at the FSFI pain sub-scale. This influences the psychometric properties of FSFI and it is recommended to exclude the pain sub-scale from the analysis in those cases. Therefore, additional analyzes will be performed on the subgroups of women who did and did not have penetrative sex during the 4 weeks prior to FSFI completion using the same statistical approaches as for hypothesis 1.

Objective 2: To identify prognostic factors associated with treatment outcome

For prognostic analyses, changes in FSFI scores between baseline and 12 months follow up as the dependent variable will be used. Further, an association model to assess possible associations between selected variables and the main outcome will be constructed. The variables that reached the level of significance of at least 0.10 in univariate analyses will be entered into multiple regression models. To avoid over-fitting, at most, one variable per 10 events will be included. In addition, highly correlated covariates (\>0.7) will not be included in the final model.

Objective 3: To assess cost-effectiveness and cost-utility of SCT vs TAU.

The cost-effectiveness analysis will be carried out from a healthcare and society perspective, comparing the treatment effect and health utilities by using the EuroQoL 5D (EQ-5D-5L) utility index. Health gains will be expressed as quality-adjusted life years (QALYs) derived from the EQ-5D-5L utility scores. Costs to the healthcare system and society (production loss) due to PVD will be estimated based on data recorded at the follow-ups including visits to general practitioner, medical specialist, physical therapist, manual therapist or other physical therapy specialist, and other therapists (e.g. chiropractor, osteopath, psychologist); number of days of hospitalization and/or rehabilitation; use of medication). Data concerning production loss will include work status in terms of working time (percentage of position), partial sick leave (percentage, duration, and reason), complete sick leave (duration and reason), disability pension (percentage, duration, and reason), unemployment (yes, no), and student/other/unknown (yes, no).

Secondary analysis

Proportion comparisons of women who experienced successful treatment outcome in SCT and TAU group will be analyzed using global perceived effect scale at 12 months follow up applying logistic regression for repeated measures. Within and between group differences in other secondary outcomes will be evaluated using linear mixed model for repeated measures.

Exploratory analysis in TAU group Participants in the TAU group may choose a variety of different treatment options, e.g. other types of physiotherapy, osteopathy, chiropractor treatment, etc. Exploratory analysis will be conducted to identify the most promising treatments with respect to improvement on the FSFI using repeated measures analysis of variance. The goal of these analyses is to identify candidate treatments for future studies.

In all analyses, the between-group mean differences with 95% confidence intervals (CI) or odds ratio (OR) with 95% CI for categorical outcomes will be reported. Missing data will be replaced using multiple imputation methods.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of provoked vestibulodynia
* Age: 18 to 35
* Must understand Norwegian well enough to be able to complete questionnaires
* Must be able to attend treatment in Oslo, Norway

Exclusion Criteria:

* Active infection in the vulvar region
* Dermatologic lesion in the vulvar region
* Presence of diagnostically confirmed psychiatric condition that necessitate treatment by a medical specialist in psychiatry of clinical psychology

Primary outcomes:
measure: Change in female sexual function index (FSFI) (Rosen et al. 2000)
timeFrame: Baseline, 6 and 12 months follow up
Secondary outcomes:
measure: Change in Participant Perceived Improvement (PGIC) (Dworkin et al. 2005)
timeFrame: 6 and 12 months follow up
measure: Change in the tampon test (Foster et al. 2009)
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in recalled pain intensity during intercourse
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in Vulvar Pain Assessment Questionnaire (VPAQ) (Dargie et al. 2017) - life interference
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in Vulvar Pain Assessment Questionnaire (VPAQ) (Dargie et al. 2017) - coping strategies
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in vulvodynia related self-efficacy
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in pain catastrophizing scale (Fernandes et al. 2012)
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in Rumination Response Scale (RRS-10) (Parola et al. 2017)
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in Hopkins Symptoms Check List (HSCL-25) (Derogatis et al.1974)
timeFrame: Baseline, 6 and 12 months follow up
measure: Change in EQ-5D-5L (Herdman et al. 2011)
timeFrame: Baseline, 6 and 12 months follow up
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo Metropolitan University
Study officials:
affiliation: Oslo Metropolitan University
name: Slawomir Wojniusz, Phd
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1080/009262300278597.
citation: 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.
citation: Foster DC, Beth Kotok M, Huang LS, Watts A, Oakes D, Howard FM, Stodgell CJ, Dworkin RH. The tampon test for vulvodynia treatment outcomes research: reliability, construct validity, and responsiveness. Obstet Gynecol. 2009 Apr;113(4):825-832. doi: 10.1097/AOG.0b013e31819bda7c.
citation: Dargie E, Holden RR, Pukall CF. The Vulvar Pain Assessment Questionnaire: Factor Structure, Preliminary Norms, Internal Consistency, and Test-Retest Reliability. J Sex Med. 2017 Dec;14(12):1585-1596. doi: 10.1016/j.jsxm.2017.10.072.
citation: Fernandes L, Storheim K, Lochting I, Grotle M. Cross-cultural adaptation and validation of the Norwegian pain catastrophizing scale in patients with low back pain. BMC Musculoskelet Disord. 2012 Jun 22;13:111. doi: 10.1186/1471-2474-13-111.
citation: Parola N, Zendjidjian XY, Alessandrini M, Baumstarck K, Loundou A, Fond G, Berna F, Lancon C, Auquier P, Boyer L. Psychometric properties of the Ruminative Response Scale-short form in a clinical sample of patients with major depressive disorder. Patient Prefer Adherence. 2017 May 12;11:929-937. doi: 10.2147/PPA.S125730. eCollection 2017.
citation: Derogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L. The Hopkins Symptom Checklist (HSCL): a self-report symptom inventory. Behav Sci. 1974 Jan;19(1):1-15. doi: 10.1002/bs.3830190102. No abstract available.
citation: Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.
citation: Rosen NO, Bergeron S, Pukall CF. Recommendations for the Study of Vulvar Pain in Women, Part 1: Review of Assessment Tools. J Sex Med. 2020 Feb;17(2):180-194. doi: 10.1016/j.jsxm.2019.10.023. Epub 2019 Dec 4.