(117) Incobotulinumtoxina for Provoked Vestibulodynia With Overactive Pelvic Floor Muscle Dysfunction: Design of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract Introduction Vulvodynia affects an estimated 8-28% of reproductive-aged women and is associated with substantial functional impairment, sexual distress, and reduced quality of life. The most common subtype, provoked vestibulodynia (PVD), is characterized by localized vestibular pain triggered by touch or penetration. Despite its prevalence, there are no FDA-approved treatments specifically for PVD, and current management strategies, such as pelvic floor physical therapy, topical therapies, or neuromodulators, are often only partially effective. Growing evidence supports the role of pelvic floor hypertonicity as a key pathophysiologic driver of pain in PVD. Up to 80% of affected patients demonstrate overactivity of the superficial and deep pelvic floor muscles, which insert at the posterior vestibule and directly contribute to painful mechanical provocation. Therapeutic approaches capable of reducing muscle tone are therefore biologically plausible targets in this population. IncobotulinumtoxinA (INA), a purified botulinum toxin type A, produces prolonged chemodenervation and muscle relaxation and has demonstrated efficacy across numerous hypertonic muscle conditions. Botulinum toxin type A has shown analgesic benefit in open-label and randomized trials for women with vestibulodynia and hypertonic pelvic floor disorders. Although incobotulinumtoxinA has not yet been evaluated in a randomized trial for PVD specifically, its pharmacologic profile supports investigation as a targeted therapy for neuroproliferative, muscle-mediated vestibular pain. Objective To evaluate the efficacy, safety, and tolerability of INA in women with PVD associated with overactive pelvic floor muscle dysfunction. Methods This is a randomized, double-blind, placebo-controlled trial enrolling 54 premenopausal women with posterior vestibular allodynia and expert-confirmed pelvic floor hypertonicity. After screening, participants are randomized 1:1 to INA (150 Units) or saline placebo. Injections are administered at Week 2 and Week 8 using a standardized posterior introitus protocol targeting the bulbospongiosus, pubococcygeus, and superficial/deep transverse perineal muscles. These muscles are selected based on their established contribution to mechanical provocation of pain in PVD. Study visits occur at Baseline, Week 2, Week 8, Week 14, and Week 24–30. At each visit, participants undergo physical examination, dilator tolerance testing, and completion of validated questionnaires; pregnancy testing is performed before each injection. Adverse events are collected at all visits and monitored through Week 30. The primary endpoint is mean change in dilator-induced pain at the Dilator Maximum Tested Size (DMTS) on an 11-point numeric rating scale. Secondary endpoints include change in the Vulvodynia Experience Questionnaire (VEQ) and the Patient Global Impression of Change (PGI-C). After the blinded phase, placebo recipients will be offered open-label INA to ensure access to active treatment. Results Trial initiation and enrollment is underway; outcome data are not yet available. Conclusions This study addresses a major therapeutic gap in vulvodynia care by evaluating a targeted treatment for women whose provoked pain is driven by pelvic floor overactivity. The design isolates a clinically relevant subgroup and integrates both mechanistic and patient-reported endpoints. Demonstrating efficacy would support adoption of INA as a nonsurgical option and lay the groundwork for Phase 3 trials and guideline-based incorporation into PVD management. Disclosure No.