Topical Ketotifen 0.25% for Secondary Vestibulodynia

Recruiting now · Phase 2 · Has a placebo group

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

In brief

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.

Key facts

Study ID

NCT07257029

Run by

Center for Vulvovaginal Disorders

People needed

54

Starts

2026-01-02

Expected to finish

2027-01-01

Last updated by the study team

2026-03-18

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• 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 it is running

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

Full record on ClinicalTrials.gov

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