Ketotifen Cream for Vulvodynia

Not yet recruiting at 2 trial locations

Overseen By Kate L Tolleson, MS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Center for Vulvovaginal Disorders

Must not be taking: Gabapentinoids, Antidepressants, Hormone therapy, others

Disqualifiers: Pregnancy, Active infections, Vulvar conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cream called ketotifen to determine if it can relieve pain for women with secondary provoked vestibulodynia (PVD), a condition causing pain during activities like intercourse or tampon use. The cream may help by targeting inflammation and nerve issues in the affected area. Women who have experienced burning or sharp pain in the vulvar area for at least six months, without signs of tissue thinning, may qualify to join. Participants will use the cream or a placebo (inactive cream) for 12 weeks to assess pain improvement. The goal is to evaluate the safety and effectiveness of this cream for treating PVD. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Is there any evidence suggesting that ketotifen cream is likely to be safe for humans?

Research has shown that ketotifen fumarate, when applied as a cream on the skin, is generally well-tolerated. Studies indicate that ketotifen does not significantly enter the bloodstream, reducing the risk of systemic side effects. In studies on allergic conjunctivitis (an eye condition), ketotifen greatly improved symptoms with few side effects.

Animal studies found that ketotifen reduces inflammation in the vulvar area, suggesting potential benefits for similar conditions in humans. No major safety concerns have been reported for ketotifen fumarate.

This clinical trial is in Phase 2, indicating that earlier studies have already assessed its initial safety. This trial will gather more information about its safety specifically for vulvodynia. Researchers will closely monitor participants for any side effects or reactions at the application site. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for vulvodynia?

Most treatments for vulvodynia involve oral medications, physical therapy, or surgical interventions, focusing primarily on managing symptoms rather than addressing potential underlying causes. Unlike these options, ketotifen fumarate cream targets mast cells directly in the affected area. It works by blocking histamine release, which may reduce inflammation and pain more effectively. Researchers are excited because this topical approach could offer a more localized and possibly quicker relief with fewer systemic side effects.

What evidence suggests that ketotifen cream might be an effective treatment for vulvodynia?

Research shows that ketotifen in cream form might help with vulvodynia by reducing inflammation and nerve issues in the vulvar area. Ketotifen stabilizes mast cells, which can cause inflammation. Animal studies have found that ketotifen lowers vulvar inflammation and reduces pain sensitivity. This trial will evaluate the effectiveness of Ketotifen Fumarate 0.25% Cream for women with secondary provoked vestibulodynia, a condition causing pain with touch or penetration. Although human studies provide limited information, these early results offer hope that ketotifen could be a possible treatment option. ^{2 3 6 7 8}

Who Is on the Research Team?

Andrew T Goldstein, MD

Principal Investigator

Center for Vulvovaginal Disorders

Are You a Good Fit for This Trial?

This trial is for adult women with secondary provoked vestibulodynia (PVD), a condition causing pain during vaginal penetration or touch. Participants must meet specific criteria without having vulvovaginal atrophy and should not have had a strong placebo response or intolerance to vehicle cream during the screening.

Inclusion Criteria

Negative vaginal culture for infection at randomization (participants with positive cultures at screening may be treated and retested)

Able to provide signed and dated informed consent

Able to read, write, understand, and complete English-language study-related forms and communicate in English

Exclusion Criteria

I cannot tolerate the smallest dilator.

I do not have an active vaginal infection.

I can be re-screened for the trial after my treatment if my condition was cured.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Single-blind Placebo Run-in

Participants apply vehicle cream twice daily to the vulvar vestibule to identify placebo responders or those intolerant to the cream

2 weeks

1 visit (in-person)

Randomized Double-blind Treatment

Participants receive either ketotifen fumarate 0.25% cream or placebo cream applied twice daily to the vulvar vestibule

12 weeks

3 visits (in-person) at Week 3, Week 9, and Week 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (virtual or in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketotifen Fumarate 0.25% Cream

Trial Overview The trial tests topical ketotifen fumarate 0.25% cream against a placebo, aiming to alleviate PVD symptoms by reducing neuroinflammation and abnormal nerve growth. Women will apply the treatment twice daily for 12 weeks, with outcomes measured by pain intensity scales, questionnaires, and physical thresholds.

How Is the Trial Designed?

Group I: Ketotifen Fumarate 0.25% Cream Experimental Treatment 1 Intervention

Participants receive topical ketotifen fumarate 0.25% cream applied 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 ketotifen cream is supplied in pre-weighed tubes and used for the full randomized treatment phase.

Group II: Placebo (Vehicle Cream) Placebo Group 1 Intervention

Participants receive the matching vehicle cream applied 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 active study cream and is supplied in pre-weighed tubes for the full randomized treatment phase.

Who Is Running the Clinical Trial?

Center for Vulvovaginal Disorders

Lead Sponsor

Trials

8

Recruited

270+

National Vulvodynia Association

Collaborator

Trials

1

Recruited

20+

Citations

1. ctv.veeva.com ctv.veeva.com/study/topical-ketotifen-025-for-secondary-vestibulodynia

Topical Ketotifen 0.25% for Secondary Vestibulodynia Preclinical studies suggest that ketotifen, a mast-cell stabilizer and histamine H1 antagonist, may reduce neuroinflammation and abnormal nerve ...

2. nva.org nva.org/news/promisingnewtreatmentsforvulvodynia/

Promising New Treatments for Vulvodynia Several animal studies have shown that ketotifen fumerate (KF) reduces inflammation of the vulva, so the next step is to test KF in women with vulvodynia.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9286136/

Characterization of Early Inflammatory Events Leading to ... Treatment with Ketotifen fumarate during inflammation suppressed the development of vulvar hypersensitivity. (A) The experimental timeline ...

4. researchgate.net researchgate.net/publication/391187707_026_KEY_OUTCOMES_OF_THE_VULVODYNIA_SUMMIT_IDENTIFYING_THERAPEUTIC_OPTIONS_FOR_FURTHER_RESEARCH_STUDY_IN_THE_TREATMENT_OF_PROVOKED_VESTIBULODYNIA

(026) KEY OUTCOMES OF THE VULVODYNIA SUMMIT Ketotifen fumarate, Resiniferatoxin, and Maresin 1 had scores between 10-12 and Luteolin, Alpha-Lipoic Acid and TPPU had a score between 8-10. TPPU was ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10107324/

Evaluation and Treatment of Vulvodynia: State of the Science Pain improved at least 50% in 80% participants with 29% having complete pain relief in at least 8 wk. Varying doses of gabapentin cream were not accounted for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07257029

Topical Ketotifen 0.25% for Secondary Vestibulodynia This trial is designed to fill that gap by rigorously evaluating efficacy, safety, and tolerability of a 0.25% ketotifen fumarate cream applied ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2006/021996s000_PharmR.pdf

Pharmacology Review(s) There are no outstanding pharmacology/toxicology issues for ketotifen fumarate. Ketotifen has been shown to have little systemic exposure ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9922628/

Topical ketotifen treatment for allergic conjunctivitis Our results showed that ketotifen contributed to a significant improvement in itching, tearing, and total signs and symptoms.