Gastroenterology
PHASE2
● Phase II
Phase 2 trial compares lidocaine/estradiol cream, nortriptyline, and combination for vestibulodynia subtypes
ClinicalTrials.gov
Published March 30, 2026
Duke University
NCT03844412 ↗
This was a phase 2, randomized, double-blinded, placebo-controlled clinical trial involving 209 women with distinct vestibulodynia subtypes (VBD-p and VBD-c). The study compared the efficacy of a peripheral treatment (5% lidocaine/5 mg/ml 0.02% estradiol compound cream), a centrally-targeted treatment (nortriptyline), and their combination against placebo cream and placebo pill controls. Primary outcomes included pain during a tampon test, change in self-reported pain via the SF-MPQ, and self-reported physical health via the SF-12 survey. A secondary aim was to determine cytokine and microRNA biomarkers predictive of treatment response.
Specific numerical results for the primary pain and quality-of-life outcomes are not reported in the provided data. Safety and tolerability data, including adverse events, serious adverse events, and discontinuation rates, are also not reported. The study's follow-up duration and specific methodological limitations are not detailed.
The study's practice relevance is framed as potential, with the assertion that positive findings would translate to improved care for women with vestibulodynia. However, in the absence of reported efficacy and safety results, no clinical conclusions can be drawn. The identification of predictive biomarkers remains an exploratory aim. Clinicians should await the publication of peer-reviewed results, including the magnitude of treatment effects and a full safety profile, before considering any changes to practice based on this trial.
Imagine living with a constant, burning pain that makes everyday activities like sitting or intimacy difficult. That's the reality for women with vestibulodynia (VBD), a chronic pelvic pain condition. Right now, there's no single, proven treatment path, leaving many women and their doctors to try different options without clear guidance.
A new study is trying to change that. Researchers enrolled 209 women with two distinct subtypes of VBD. They're comparing three approaches: a compound cream applied directly to the painful area, a pill that works on the central nervous system, and a combination of both. The goal is to see which strategy best reduces pain during a specific test and, more importantly, improves how women feel in their daily lives based on their own reports.
This is a carefully designed, phase 2 trial, which means it's an important step in figuring out if these treatments are worth pursuing in larger studies. The researchers are also looking for biological clues in the blood—like specific proteins and genetic markers—that might predict who will respond best to which treatment. It's a search for more personalized care.
It's crucial to remember that the main results from this head-to-head comparison aren't available yet. We don't know if one treatment worked better than the others, or what side effects women might have experienced. The promise here is in the rigorous question being asked: by directly testing different strategies, this study could eventually help match women with the treatment most likely to ease their specific pain.
What this means for you: A clinical trial is testing different pain strategies for chronic pelvic pain; results are pending.
View Original Abstract ↓
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
