Phase 2 trial compares lidocaine/estradiol cream, nortriptyline, and combination for vestibulodynia subtypesCan a cream or pill help women with chronic pelvic pain?

ClinicalTrials.gov Published April 3, 2026 Study authors: Duke University NCT03844412 ↗ Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain

AI-generated summary of the cited source, checked by automated accuracy review. How we work

Key Takeaway

Await full results from this phase 2 trial comparing topical and systemic treatments for vestibulodynia subtypes.

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 5% lidocaine/0.02% estradiol compound cream, nortriptyline, and combined treatments against placebo cream and placebo pill over a follow-up period of 52.3 months. Primary outcomes were the Pain Score During the Tampon Test, change in self-reported pain via the Short Form-McGill Pain Questionnaire (SF-MPQ), and self-reported physical health via the SF-12 Health Survey (SF12v2). A secondary aim was to determine cytokine and microRNA biomarkers predictive of treatment response.

No efficacy results, effect sizes, absolute numbers, or statistical significance for the primary or secondary outcomes are reported in the provided data. The study's main findings on pain alleviation and patient-reported outcomes remain unknown from this summary.

Safety and tolerability data, including adverse events, serious adverse events, and discontinuation rates, are also not reported. The study was funded by Duke University as the lead sponsor. The provided text states no specific limitations, but the absence of reported results is a significant constraint on interpretation.

Regarding practice relevance, the provided text suggests positive findings would translate to improved care, but no evidence is presented to support this claim. Clinicians should await the publication of complete results, including efficacy and safety data, before considering any changes to practice. The long 52-month follow-up is notable but does not compensate for the lack of reported outcomes.

Imagine living with pain so severe that something as simple as using a tampon is excruciating. That's the reality for women with vestibulodynia (VBD), a chronic pelvic pain condition. Researchers at Duke University wanted to see if they could find a better way to help. They enrolled 209 women with different subtypes of VBD in a carefully designed trial to compare three approaches: a cream containing lidocaine and estradiol, a pill called nortriptyline, or both treatments together. The goal was to see which one best reduced pain and improved quality of life over more than four years of follow-up. The study also looked for biological markers in the body that might predict who would respond to which treatment. This is a crucial step toward more personalized care. However, the specific results of this trial—how much pain improved, which treatment worked best, and what side effects occurred—are not yet available. While the hope is that this work will lead to better pain management, we're still waiting for the data to see what it actually found.

What this means for you:

Study tested pain treatments for women with chronic pelvic pain; results pending.

Study Details

Study typePhase2

Sample sizen = 209

EvidenceLevel 3

Follow-up52.3 mo

PublishedMar 2026

TrialNCT03844412

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

Phase 2 trial compares lidocaine/estradiol cream, nortriptyline, and combination for vestibulodynia subtypesCan a cream or pill help women with chronic pelvic pain?

Study Details

Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic stroke

Tenecteplase improves stroke recovery but increases bleeding risk in late treatment window

Clinical research that matters. Delivered to your inbox.

Phase 2 trial compares lidocaine/estradiol cream, nortriptyline, and combination for vestibulodynia subtypesCan a cream or pill help women with chronic pelvic pain?

More on Vestibulodynia

Study Details

Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic stroke

Tenecteplase improves stroke recovery but increases bleeding risk in late treatment window

Clinical research that matters. Delivered to your inbox.

Related in Neurology

From Other Specialties