Topical Ketotifen 0.25% for Secondary Vestibulodynia

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.

Conditions

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

Interventions

DRUG

Ketotifen 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.

DRUG

Placebo (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.

Sponsors & Collaborators

• National Vulvodynia Association

  collaborator OTHER

• Center for Vulvovaginal Disorders

  lead OTHER

Principal Investigators

• Andrew T Goldstein, MD · Center for Vulvovaginal Disorders

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-02

Primary Completion

2026-08-01

Completion

2027-01-01

FDA Drug

Yes

Countries

• United States

Study Locations