Topical ketotifen 0.25% for secondary vestibulodynia

A Multi-center, Randomized, Double-blind, Placebo-controlled Trial of Topical Ketotifen Fumarate 0.25% Cream for Females With Secondary Vestibulodynia

This Phase 2 trial will test whether applying ketotifen 0.25% cream to the vulvar vestibule reduces pain in adult women with secondary provoked vestibulodynia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Center for Vulvovaginal Disorders (other)
• Locations: 3 sites (Washington D.C., District of Columbia and 2 other locations)
• Trial ID: NCT07257029 on ClinicalTrials.gov

What this trial studies

This Phase 2, multicenter, randomized, double-blind, placebo-controlled trial compares topical ketotifen 0.25% cream to a matching vehicle in adult women with secondary provoked vestibulodynia. Approximately 54 participants will complete a screening and a 2-week single-blind placebo run-in, and eligible non–placebo-responders will be randomized with blinded outcome assessment. The drug is a mast-cell stabilizer and H1 antagonist intended to reduce local neuroinflammation and pathological nerve proliferation in the vestibular mucosa. Safety, pain reduction, and function-related outcomes will be measured across study visits at participating centers.

Who should consider this trial

Good fit: Women aged 18 years or older with secondary provoked vestibulodynia of at least 6 months' duration who meet ISSVD/ISSWSH/IPPS criteria, have moderate-to-severe vestibular tenderness on exam, no vulvovaginal atrophy, and a BMI between 18.5 and 32 kg/m² are ideal candidates.

Not a fit: Patients with primary vestibulodynia, active vulvovaginal infection or untreated atrophy, a strong placebo response during the run-in, significant uncontrolled comorbidities, or BMI outside the eligible range may not benefit or may be ineligible.

Why it matters

Potential benefit: If effective, the cream could offer a non-surgical, mechanism-based topical option to reduce vestibular pain and potentially avoid or delay invasive procedures like vestibulectomy.

How similar studies have performed: Preclinical and translational data support the proposed mechanism, but randomized clinical trial evidence of ketotifen for vestibulodynia is limited, so the clinical approach remains relatively novel.

Eligibility criteria

Inclusion Criteria:

* Female participants ≥18 years of age
* Able to provide signed and dated informed consent
* Able to read, write, understand, and complete English-language study-related forms and communicate in English
* Has a stable address and is available for the duration of the study
* In good general health based on medical history
* Willing to comply with all study procedures
* Body mass index (BMI) between 18.5 kg/m² and 32.0 kg/m² (inclusive)
* Meets ISSVD/ISSWSH/IPPS criteria for secondary provoked vestibulodynia, including: 6 continuous months of vulvar symptoms (insertional dyspareunia, pain with tampon insertion, or pain to touch); moderate to severe vestibular tenderness to light touch on physical exam
* No evidence of vulvovaginal atrophy
* If atrophy is present, must complete ≥12 weeks of topical hormone therapy and be re-screened to confirm resolution before enrollment
* Negative vaginal culture for infection at randomization (participants with positive cultures at screening may be treated and retested)

Exclusion Criteria:

* Pregnancy or lactation
* Unable to tolerate the smallest dilator during baseline dilator assessment
* Active vaginal infection (Candida, BV, trichomonas, HSV)
* May re-screen after treatment and documented cure
* Active cutaneous disease of the vestibule
* Current presentation of other painful vulvar conditions, including:

Pudendal neuralgia Lichen sclerosus Lichen planus Plasma cell vulvitis Vulvar intraepithelial neoplasia Sjögren's disease Desquamative inflammatory vaginitis

* Hypoestrogenic states (e.g., vulvar atrophy due to menopause or medications)
* History of significant vestibular or vaginal surgery, including:

Vestibulectomy Perineoplasty Bladder neck suspension Anterior/posterior colporrhaphy Pudendal nerve neurolysis Ablative or fractional laser procedures

* Initiation or planned change in any of the following within 30 days before screening or during the study:

Gabapentinoids Tricyclic antidepressants SSRIs or SNRIs Hormone replacement therapy Systemic or local muscle relaxants (benzodiazepines, baclofen, botulinum toxin, cyclobenzaprine, CBD suppositories) Pelvic floor physical therapy

* Use of another investigational drug or intervention within the past 3 months
* Positive vaginal culture during the study requiring two or more treatments (per protocol, second infection leads to termination)
* Any condition or factor that, in the opinion of the investigator, would interfere with study participation or safety

Where this trial is running

Washington D.C., District of Columbia and 2 other locations

• The Center for Vulvovaginal Disorders - Washington, DC — Washington D.C., District of Columbia, United States (RECRUITING)
• The Center for Vulvovaginal Disorders — Tampa, Florida, United States (RECRUITING)
• The Center for Vulvovaginal Disorders - New York — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Andrew T Goldstein, MD — Center for Vulvovaginal Disorders
• Study coordinator: Andrew T Goldstein, MD

Conditions: Provoked Vestibulodynia, Secondary Provoked Vestibulodynia, Vulvodynia, Vulvary Pain Disorders, Neuroproliferative Vestibulodynia, Mast Cell-mediated Neuroinflammation, Instertional Dyspareunia, ketotifen fumarate