Phase 2 trial compares lidocaine/estradiol cream, nortriptyline, and combination for vestibulodynia subtypes

Status: COMPLETED | Phase: PHASE2 Condition(s): Vestibulodynia, Temporomandibular Disorder, Fibromyalgia Syndrome, Irritable Bowel Syndrome, Migraines Intervention(s): 5% lidocaine/5 mg/ml 0.02% estradiol compound cream (DRUG), Nortriptyline (DRUG), Placebo cream (DRUG), Placebo pill (DRUG) Vestibulodynia (VBD) is a complex chronic vulvar pain condition that impairs the psychological, physical, and sexual health of 1 in 6 reproductive aged women in the United States. Here, the investigators plan to conduct a randomized, double-blinded, placebo-controlled clinical trial to 1) compare the efficacy of peripheral (lidocaine/estradiol cream), centrally-targeted (nortriptyline), and combined treatments in alleviating pain and improving patient-reported outcomes and 2) determine cytokine and microRNA biomarkers that predict treatment response in women with distinct VBD subtypes. Positive findings from this study will readily translate to improved patient care, permitting the millions of women with VBD, their partners, and their clinicians to make more informed decisions about pain management. Detailed: Vestibulodynia (VBD) is a chronic pelvic pain condition that affects 1 in 6 reproductive aged women, yet remains ineffectively treated by standard trial-and-error approaches. The investigators have identified two distinct VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p) subtype characterized by localized pain specific to the vulvar vestibule, and 2) VBD central (VBD-c) subtype characterized by pain at both vaginal and remote body regions. Preliminary data further demonstrate that VBD-p and VBD-c subtypes differ with respect to patient reported outcomes (e.g., physical and mental health), production of cytokines (intracellular proteins that regulate the activity of pain nerves and inflammatory processes), and expression of microRNAs (small non-codin Primary Outcome(s): Pain Score During the Tampon Test; Change in Self-reported Pain Via the Short Form- McGill Pain Questionnaire (SF-MPQ); Self-reported Physical Health Via SF-12 Health Survey (SF12v2) Enrollment: 209 (ACTUAL) Lead Sponsor: Duke University Start: 2019-11-04 | Primary Completion: 2024-03-13 Results posted: 2026-03-19