RecruitingPhase 2NCT07257029

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

Sponsor

Center for Vulvovaginal Disorders

Enrollment

54 participants

Start Date

Jan 2, 2026

Study Type

INTERVENTIONAL

Conditions

Vulvodynia Provoked Vestibulodynia Secondary Provoked Vestibulodynia Vulvary Pain Disorders Neuroproliferative Vestibulodynia Mast Cell-mediated Neuroinflammation Instertional Dyspareunia

Summary

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.

Eligibility

Sex: FEMALEMin Age: 18 Years

Inclusion Criteria11

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 Criteria15

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

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Interventions

DRUGKetotifen Fumarate 0.25% Cream

Participants apply topical ketotifen fumarate 0.25% cream as a thin layer to the vulvar vestibule twice daily (approximately every 8-12 hours) for 12 weeks after completing the 2-week placebo run-in period. The cream is provided in pre-weighed tubes and used throughout the randomized treatment phase.

DRUGPlacebo (Vehicle Cream)

Participants apply the matching vehicle cream as a thin layer to the vulvar vestibule twice daily (approximately every 8-12 hours) for 12 weeks following completion of the 2-week placebo run-in period. The placebo cream is identical in appearance and packaging to the ketotifen cream and is provided in pre-weighed tubes for use throughout the randomized treatment phase.