Clinical Research Directory

Topical Ketotifen 0.25% for Secondary Vestibulodynia

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of topical ketotifen fumarate 0.25% cream in adult women with secondary provoked vestibulodynia (PVD). Secondary PVD is a chronic vulvar pain condition characterized by burning or sharp pain with vaginal penetration (e.g., intercourse, tampon use) and touch of the vulvar vestibule, often following recurrent infections or topical irritant exposures. Preclinical studies suggest that ketotifen, a mast-cell stabilizer and histamine H1 antagonist, may reduce neuroinflammation and abnormal nerve growth in the vulvar vestibule, offering a mechanism-based, non-surgical treatment option. Approximately 54 women aged 18 years and older who meet ISSVD/ISSWSH/IPPS criteria for secondary PVD without vulvovaginal atrophy will be enrolled. After a 1-week screening period, all participants will complete a 2-week single-blind placebo run-in; those with a strong placebo response or intolerance to vehicle cream will not be randomized. Eligible participants will then be randomized 1:1 to receive ketotifen fumarate 0.25% cream or matching placebo cream applied twice daily to the vulvar vestibule for 12 weeks. The primary outcome is change from baseline to Week 15 in pain intensity with the baseline dilator maximum tested size (DMTS), measured on an 11-point numeric rating scale. Secondary outcomes include changes in Vulvodynia Experience Questionnaire (VEQ) scores, vestibular pain thresholds measured by Wagner algometry, and participant-reported meaningful benefit at the end of treatment. Safety assessments will include adverse events, application-site reactions, physical examinations, vital signs, and pregnancy testing. This study will provide the first controlled clinical data on topical ketotifen for secondary PVD and inform the feasibility of larger registration trials.

A Phase 2 Study to Evaluate the Efficacy and Safety of Pudafensine in Vulvodynia (Provoked Vestibulodynia)

The study (IP2015CS05) is a randomised, double-blind, placebo-controlled, 4-way cross-over trial studying the efficacy and safety of single dose administration of pudafensine in vulvodynia (provoked vestibulodynia) patients.

Prospective Data Bank Creation to Study Vaginal Conditions

The purpose of this study is to identify and elucidate the pattern and perhaps role of atypical proteins, cytokines and vaginal microbial flora in the pathogenic mechanisms involved in the development of vulvodynia, recurrent fungal and bacterial vaginosis and preterm labor.

Multidisciplinary Treatment of Chronic Vulvar Pain

Vulvodynia (i.e. chronic vulvar pain without identifiable cause) is a heterogeneous clinical entity with a complex multifactorial causation. It is long lasting and difficult to treat, and the general consensus of current guidelines states that patients with vulvodynia benefit from a compound multidisciplinary intervention targeting mucosal hypersensitivity, pelvic muscle floor dysfunction and general pain management. However, there is little empiric evidence to support this recommendation. This will be a randomized controlled trial comparing multidisciplinary treatment with standard care for women with vulvodynia.

Use of Topical Testosterone and Estrogen vs Estrogen Alone in Vulvodynia: a Randomized Controlled Trial

We are looking to see if patients using both topical testosterone and estrogen will have a greater improvement in pain with vaginal penetration compared to those using topical estrogen alone.

Young Vulvodynia: Effect and Efficacy of Multimodal Treatment.

The aim of this SCED-study is to evaluate a multimodal treatment for vulvodynia in young women. The main questions it aims to answer are: Is multimodal treatment effective for provoked vulvodynia in young women? How is multimodal treatment experienced by young women with vulvodynia? Participants will respond to frequent questionnaires (two times a week) during a baseline period of 4,5 or 6 weeks, as well as during their treatment period ( a total of 25 weeks). In addition they will respond to pre-, post-treatment and 6 month follow-up questionnaires.

Vaginal Ecosystem and Network in the United States Study

The central premise of this study is that the intricate balance and diversity of the vaginal microbiome plays a pivotal role in the onset, progression, and severity of various gynecological conditions. Specifically, the research aims to investigate how imbalances in microbial communities, such as the overgrowth of pathogenic bacteria or the depletion of beneficial ones, are linked to conditions like Bacterial Vaginosis, Candidiasis, Urinary Tract Infections, Vaginal Atrophy, and others. By employing PCR testing and the outcomes of next-generation sequencing (NGS) of the microbiome, the study seeks to identify distinct microbial profiles and patterns that are characteristic of each condition. This nuanced understanding is expected to lead to more accurate and early diagnosis, facilitating personalized and effective treatment strategies that go beyond the conventional, often indiscriminate use of antibiotics.

Biomodulation and Rehabilitation Interventions to TarGet Pelvic Health

This trial will provide evidence for the effective management of pain and pain-related domains among those who experience provoked vestibulodynia (PVD) using photobiomodulation (PBM) and multimodal physiotherapy (mPT) in a randomized controlled trial (RCT). PVD is the most common subcategory of vulvovaginal pain experienced during sexual and non-sexual activities, affects the psychological and sexual health of an astounding one in five Canadian women, yet access to evidence-informed management approaches is limited. We will employ four intervention groups: PBM, sham PBM (control), PBM combined with mPT, and mPT with sham PBM to evaluate the effectiveness of each approach on its own and the two approaches in combination. Among those who experience PVD, we seek to answer: 1. Relative to baseline and to sham PBM, does a 14-week intervention involving PBM, mPT, or a combination of mPT and PMB reduce vulvar pain severity reported on the Vulvar Pain Assessment Questionnaire (VPAQ)? 2. Is a combined mPT and PBM intervention more effective than mPT or PMB alone when considering vulvar pain severity and/or related domains as measured through VPAQ? 3. Are positive changes in vulvar pain severity and related domains observed following a 14-week intervention involving PBM, mPT or a combination of PBM and mPT retained at 6 months and at 1 year? Secondary objectives include determining the effectiveness of PBM, mPT, and mPT combined with PBM relative to sham PBM on: Patient Global Impression of Change (PGIC), pain sensitivity measured using provocative tests, the other domains of the VPAQ, sexual function, as well as investigating mediating effects of psychosocial variables (central sensitization index, chronic pain acceptance), gender identity, and the presence of vaginismus on patient response to mPT, PBM and mPT combined with PBM. Lastly we will monitor patient satisfaction with the interventions, adherence to the interventions, and any adverse events.

Vestibulodynia At High Resolution: Omics Approach to Improve Diagnosis

According to recent nomenclature, vulvodynia is vulvar pain without a clear identifiable cause persisting for at least 3-months and distinguished from vulvar pain caused by a specific disorder (inflammatory, neoplastic, traumatic). Vulvodynia can be provoked (when the pain is felt after touching the area), or unprovoked (pain is constant). Localized provoked vulvodynia of the vestibule, known as vestibulodynia (VBD), is the most common manifestation of the disease (about 80%). Data collected suggests that up to 16% of women, particularly sexually active reproductive-aged women, suffers from this condition. Despite affecting almost 1 out of 8 women of all ages, vulvodynia remains completely unacknowledged to the most. These data highlight that VBD cannot be considered a rare disease, but it rather is a high frequency women's health condition, albeit neglected and hard to diagnose because of a lack of obvious markers. Despite the paucity of molecular data, studies about pathogenesis of VBD have highlighted several risk factors including inflammation, recurrent vulvovaginal infections and microbiota dysfunction, mucosal nerve fiber proliferation, hormonal alterations, pelvic floor muscle dysfunction, central pain mechanisms, and genetic factors. A recent study has highlighted that, compared to healthy controls, women with VBD demonstrated differences primarily in vaginal (but not plasma) concentrations of metabolites of the sphingolipid signaling pathways, suggesting localized effects in vagina and vulvar vestibule rather than systemic effects. The current prevalent theory on the etiology of VBD is that during or after an initial and persistent vulvovaginal insult (infection, microtrauma, allergic reaction), a "susceptible" individual is then unable to successfully clear the inflammation process that alters and sensitizes the neural tissue in the vestibular area, resulting in localized allodynia and hyperalgesia. The under-diagnosis of VBD is the result of different factors including practical, cultural, sociological and psychological ones. The women with VBD confirmed that healthcare provider knowledge and attitudes as well as system challenges (specialist and allied healthcare provider availability) are major barriers to timely diagnosis, mainly due to lack of diagnostic tests. For instance, many patients do not seek treatment due to feelings of inadequacy, invalidation, isolation or guilt. This attitude also has a cultural background that is rooted in shame, in the endurance of pain, in embarrassment and resulting silence of patients, dismissal of vulvar pain as a "psychological disorder" by clinicians have resulted in widespread ignorance about this disabling condition. Finally, one of the most important, and doubtlessly the easiest one to solve, is the lack of either molecular or cellular markers of the disease itself. Unfortunately the VBD diagnosis always comes too late, when the mechanism of aberrant immune response already has caused the irreversible nervous sprouting in the vulvar vestibule and the chronicization of the symptoms has already happened. This delayed diagnosis increases the women's risk for sexual dysfunction and diminishes their quality of life. The VBD diagnosis is generally a diagnosis of exclusion, where basically all other possible differential diagnoses have been excluded and this is what is "left over". Many markers of inflammation were investigated without significant results, likely because the method employed in the study was focused on few pre-selected targets and an unbiased analysis has not been performed, yet. For all these reasons, the search for suitable diagnostic markers of VBD remains a high but unmet research priority. In the NGS era the absence of genomic study of VBD is despicable. RNA-sequencing of vestibule vaginae (vestibular) cell swab is a pain-free method that we already tested and could allow the identification of diagnostic markers of VBD for the development and the optimization of a reliable and quantifiable diagnostic test. In this context we plan to perform transcriptomic analysis integrated with the state-of-the-art single cell omic analysis on VBD patients and healthy controls to unbiasedly identify specific VBD markers. Moreover, considering the different pathogenesis and the range of symptoms and severity of the disease, with these markers we also aim at stratifying different groups of VBD. This stratification will lay the foundation for further studies to move patients towards a real personalized medicine. This analysis has never been performed on VBD patients with this global approach and at such high resolution. The results of our project will help the clinicians in VBD diagnosis, in therapy direction and in the earlier identification of patients with higher risk to develop chronic VBD, thus helping to build a preventive strategy to avoid the progression and chronicization of the symptoms

Lasertherapy for Vulvodynia

The study aims to assess the efficacy, acceptance and safety profile of vulvovaginal laser therapy in women with vulvodynia.

Efficacy of High Intensity Laser for Provoked Vestibulodynia

This is a multicenter randomized controlled trial (RCT) investigating the effects of laser treatments in women suffering from provoked vestibulodynia compared to a sham-laser treatment. Following their enrollment in the study, participants will undergo a gynecological examination for confirmation of their diagnoses. Eligible participants will then be asked to complete a consent form and the baseline assessment. The baseline assessment consists of the completion of validated questionnaires (outcome measures). Participants will be randomized into the laser group or sham-laser group. The laser group will receive 12 sessions of active high intensity laser therapy (HILT) (30 minutes biweekly for 6 consecutive weeks). The sham-laser group will receive 12 sessions (30 minutes biweekly for 6 consecutive weeks) of laser therapy using a deactivated probe. Outcome measures (validated questionnaires) will also be assessed 2 weeks post-treatment as well as 6 months post-treatment (follow-up assessment).

Acupuncture in a Multidisciplinary Approach for Vulvodynia and Chronic Pelvic Pain

Background: Vulvodynia and chronic pelvic pain (CPP) are common and challenging gynecologic pain syndromes. A multidisciplinary approach is recommended. Study aim: To study the effectiveness of acupuncture as part of a multimodal treatment for women with vulvodynia and CPP. Design: Randomised controlled clinical study Study Population: Recruitment from a University outpatient clinic Study groups: Participants will be randomised (1:1) * Acupuncture group * Waiting list control group Sample size: 68 patients Study outcome * Subjective Pain Perception (VAS) * Health-related quality of life (questionnaires)

Vestibulectomy Surgical Techniques Comparison Study

Vestibulectomy Surgical Techniques Comparison Study

Light Emitting Diode in the Treatment of Vulvodynia

Vulvar pain can be related to a specific cause (inflammation, cancer, trauma, infection) or can be classified as vulvodynia, when vulvar pain is idiopathic and lasts for at least three months. The main symptoms reported are pain, burning, erythema, increased sensitivity, itching and burning, which affect the quality of life, psycho-emotional well-being, relationships and sexual function of these women. Photobiomodulation has been described in the literature as an alternative to treat pain. Our group has studied blue LED for some vulvovaginal dysfunctions and, due to the positive sensory effects observed in patients with vaginal stenosis and genitourinary syndrome of menopause, it is hypothesized that this technique could also bring beneficial effects for women with vulvodynia. A pilot study will be carried out, with descriptive data, with 10 women with vulvodynia. Participants will be evaluated with a basic anamnestic questionnaire and sociodemographic data. The following questionnaires will be used: Female Sexual Function Index (FSFI), Sexual Quotient - Female Version, Vulvar Pain Assessment Questionnaire. After answering the questionnaires, the volunteer will undergo a perineal physical assessment by an experienced physiotherapist, which includes a) inspection of the genital region, reflex tests, assessment of the functions of the pelvic floor muscles, b) the cotton swab test to evaluate painful sensitivity in the vestibule, c) the tampon test to evaluate painful sensitivity in the introitus and vaginal canal. Pain assessments will be quantified by the visual analogue pain scale (VAS), which ranges from 0 (no pain) to 10 (maximum pain). At the end of the treatment, the participant will answer the questionnaires again, undergo reassessment of pain sensitivity in vulva, introitus and vaginal canal, of the function of the pelvic floor muscles and will be asked "What is your perception of improvement" and "What is your level of satisfaction with the treatment?". The answers will be giving according to a Likert Scale of five points. The LED application protocol will be carried out with external use equipment model Antares, from the company IBRAMED (Amparo, São Paulo, Brazil), with a cluster G2 applicator. The power will be 450mW/cm2 and dose 5J/cm2 for 2 minutes and 13 seconds (automatic programming) in 450nm waves (blue wavelength). The treatment consists of eight sessions, carried out daily, except on weekends.

Effectiveness of Low-dose Naltrexone in Patients With Different Types of Vulvodynia

Vulvodynia (Vd) is chronic functional vulvar pain, with prevalence of 3-16% and unclear etiopathology. Although Vd significantly deteriorates quality of life, the problem is marginalized, no pharmacologic treatment standards exist. Naltrexone hydrochloride is a specific opioid antagonist with slight agonist activity. There is growing body of evidence supporting the effectiveness of low-dose naltrexone (LDN) in different types of chronic pain. The main goal of this trial is to test the effect of LDN on pain perception and quality of life in women with different types of Vd. Half of the study population receives LDN and the remaining patients take placebo, according to randomization list. This RTC is quadruplet blinded.