Somatocognitive Therapy in Treatment of Provoked (Localized) Vestibulodynia - Randomized Clinical Trial (ProLoVe Study)

Study Overview
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Brief Summary
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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
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Objectives: The main objectives of the ProLoVe study are: To assess clinical effectiveness of somatocognitive therapy (SCT) versus treatment as usual (TAU) in provoked vestibulodynia (PVD). To identify prognostic factors associated with treatment outcome 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.

Official Title
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Effectiveness and Cost-utility of Somatocognitive Therapy Versus Treatment as Usual for Provoked (Localized) Vestibulodynia - a Randomized Clinical Trial (ProLoVe Study)

Conditions
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Vulvodynia, Vestibulodynia

Intervention / Treatment
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* Other: Somatocognitive physiotherapy
* Other: Treatment as usual


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group randomized clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somatocognitive physiotherapy<br>Somatocognitive therapy is a multi-modal physiotherapy intervention utilized for women with longstanding chronic pelvic pain and provoked vestibulodynia developed at the beginning of the 2000s as a collaboration between the department of psychosomatic medicine, Oslo University Hospital (OUH) and department of physiotherapy (OsloMet) | Other: Somatocognitive physiotherapy<br>* The main intervention areas include: education about the PVD, healthy vulvo-vaginal and sexual behaviors, nature of chronic pain and factors influencing pain intensity bodily exercises and techniques increasing body awareness, ability to relax and control muscle tension and respiration pattern in different situations techniques to cope with emotions and thoughts related to bodily experiences and to PVD structured homework assignments promoting application of the learned techniques in daily situations and gradual exposure of the patient to activities associated with pain. Participants will be offered maximally 15 treatment sessions. No minimal number of sessions is set. Treatment will be conducted by female physiotherapists experienced in treating long-standing pain conditions.<br>|
| Active Comparator: Treatment as usual<br>The participants randomized to the treatment as usual group will follow available treatment options based on the current recommendations from Vulva clinic at Oslo University Hospital, a center that is specialized in treatment of vulvar conditions. | Other: Treatment as usual<br>* The participants will follow the current treatment advice as recommended by the Vulva Clinic at OUH, a tertiary health care center specialized in treatment of vulvar disorders. Advice include guidance about the management of PVD as a condition, use of medication, physiotherapy, sexologist and psychological counseling, usage of internet resources (vulva.no) and others. Participants will be free to pursue treatment options of their choice. The type of treatment, number of treatments and medication usage will be monitored by bi-weekly electronic forms during the whole study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in female sexual function index (FSFI) (Rosen et al. 2000) | A multidimensional scale assessing key dimensions of female sexual function. The FSFI is a 19-item self-report questionnaire designed to measure sexual functioning in women. It assesses six domains of sexual function: sexual desire, sexual arousal, lubrication, orgasm, satisfaction, and pain (i.e., pain associated with vaginal penetration). Higher scores indicate better sexual functioning. | Baseline, 6 and 12 months follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Participant Perceived Improvement (PGIC) (Dworkin et al. 2005) | Participants are asked to rate on a 7-points Likert scale how much their condition has changed since baseline measurement. Answering alternatives: very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse | 6 and 12 months follow up | 
| Change in the tampon test (Foster et al. 2009) | The tampon test measures vulvar pain intensity during insertion and removal of a standard sanitary tampon. At each assessment time (baseline, 6 and 12 months follow up), the test will be performed three times at home during a 7-day period, on days 1, 4 and 7. A mean value of these 3 measurements will be used as a measure of pain sensitivity. Pain intensity is recorded on the Numeric Rating Scale (0-10) where 0 is no pain and 10 is the worst pain imaginable. | Baseline, 6 and 12 months follow up | 
| Change in recalled pain intensity during intercourse | Participant is asked to score on a Numeric Rating Scale (0-10) how intense was the pain during last intercourse, where 0 is no pain and 10 is the worst pain imaginable. | Baseline, 6 and 12 months follow up | 
| Change in Vulvar Pain Assessment Questionnaire (VPAQ) (Dargie et al. 2017) - life interference | VPAQ is developed to assist in the assessment and diagnosis of vulvodynia. Life interference sub-scale describes impact of vulvodynia on daily living. It consists of 11 questions addressing different domains of daily functioning. Each question is scored on a 6-points Likert scale with a higher score indicating higher negative impact of vulvodynia on daily activities | Baseline, 6 and 12 months follow up | 
| Change in Vulvar Pain Assessment Questionnaire (VPAQ) (Dargie et al. 2017) - coping strategies | VPAQ - coping strategies sub-scale consists of 12 statements describing different pain-coping strategies. Each statement is scored on a 5-points Likert scale referring to how often a specific strategy is used. A higher score indicate more frequent use of a given strategy. | Baseline, 6 and 12 months follow up | 
| Change in vulvodynia related self-efficacy | The scale will be assessed to record participant's belief in her ability to cope with the vulvodynia symptoms on her own. The scale is based on one question scored on 5-points Likert scale with higher scores indicating higher belief in woman's ability to cope with her symptoms. | Baseline, 6 and 12 months follow up | 
| Change in pain catastrophizing scale (Fernandes et al. 2012) | The pain catastrophizing scale is a self-report measure consisting of 13 items scored from 0 to 4. The higher the score, the more catastrophizing thoughts are present. It assesses an impact of negative cognition's and catastrophizing on pain experience. This version of the scale has been specifically adapted for pain related to vulvodynia. | Baseline, 6 and 12 months follow up | 
| Change in Rumination Response Scale (RRS-10) (Parola et al. 2017) | Rumination and worry express a method of coping with negative emotions and feelings that is characterized by self-focused attention, repetitive focus on negative emotions and self-reflection. RSS-10 includes 10 questions scored on a 4-points Likert scale. The higher scores indicate more worry and rumination. | Baseline, 6 and 12 months follow up | 
| Change in Hopkins Symptoms Check List (HSCL-25) (Derogatis et al.1974) | HSCL-25 evaluates psychological distress related to the anxiety and depression symptoms. It consists of 25 questions scored on a 4-points Likert scale. Higher scores indicate higher levels of psychological distress. | Baseline, 6 and 12 months follow up | 
| Change in EQ-5D-5L (Herdman et al. 2011) | EQ-5D-5L is used to assess health related quality of life and/or cost-effectiveness of assessed interventions. It consists of 5 domains scored on 5-points Likert scale with higher scores indicating lower quality of life. Additionally 100 points NRS scale is used for evaluation of current health status with higher score indicating better health. | Baseline, 6 and 12 months follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Provoked vestibulodynia, Dyspareunia, Somatocognitive therapy, Physiotherapy, Randomised clinical trial, Women's health, Sexual dysfunction, Pain management