A Phase 2 interventional study of 5% lidocaine/5 mg/ml 0.02% estradiol compound cream and Nortriptyline in Vestibulodynia, Temporomandibular Disorder and Fibromyalgia Syndrome, sponsored by Duke University. Completed at 2 sites in United States. Open to female participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2026-03-19.
Sponsored by Duke University · Phase 2, Interventional, and Treatment
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.
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-coding RNA molecules that regulate gene expression). Women with VBD-p exhibit normal psychological profiles; balanced circulating pro- and anti-inflammatory cytokines; and dysregulation in microRNAs that regulate the expression of genes in estrogen pathways. In contrast, women with VBD-c report decreased functional status and increased somatization; increased pro-inflammatory but not anti-inflammatory cytokines; and dysregulation in microRNAs that regulate the expression of genes relevant to muscle, nerve, and immune cell function. Based on these data, the investigators hypothesize that two VBD-p and VBD-c subtypes will preferentially respond to peripheral, central, or combined treatments and can be distinguished by cytokine and microRNA profiles. These hypotheses will be tested in a phase III clinical trial that evaluates diverse treatment strategies in women with VBD-p and VBD-c. Participants will be randomly assigned to one of four parallel arms: peripheral treatment with 5% lidocaine + 0.5 mg/ml 0.02% estradiol compound cream, 2) central treatment with the tricyclic antidepressant nortriptyline, 3) combined peripheral and central treatments, or 4) placebo. The treatment phase will last 4 months (with a 6-week titration at treatment initiation and 2-week taper period at 4 months), with outcome measures and biomarkers assessed at 4 time points (0, 2, 4, and 6 months). First, the investigators will compare the efficacy of treatments in alleviating pain among women with VBD-p and VBD-c using standardized tampon insertion with a numeric rating scale and self-reported pain on the McGill Pain Questionnaire. Next, the investigators will compare the efficacy of treatments in improving perceived physical, mental, and sexual health among women with VBD-p and VBD-c using standardized questionnaires. Finally, investigators will measure cytokines and microRNAs in women with VBD-p versus VBD-c using multiplex assays and RNA sequencing, and determine the ability of these biomarkers to predict treatment response. Successful completion of the proposed work will provide new insights into the mechanisms that drive pain perception and treatment response in two distinct VBD subtypes, and determine the efficacy of peripheral, central, and combined therapies in reversing this pain. Such findings will readily translate to improved patient care, permitting the millions of women with VBD, their partners, and clinicians to make more informed decisions about pain management.
117 studies on the registry are indexed under Vulvodynia; 21 are open to participants now.
This study's enrollment of 209 is above the median of 46 across 89 interventional studies indexed under Vulvodynia.
Browse Vulvodynia studies →Duke University is the lead sponsor of 2,063 studies on the registry; 273 are open to participants now.
Of its 204 completed or terminated interventional studies of FDA-regulated products, 167 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Meeting criteria for diagnosis of VBD based on:
Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
5% lidocaine/5 mg/ml 0.02% estradiol compound cream
Drug: 5% lidocaine/5 mg/ml 0.02% estradiol compound cream · Drug: Placebo pill
tricyclic antidepressant nortriptyline pill
Drug: Nortriptyline · Drug: Placebo cream
5% lidocaine/5 mg/ml 0.02% estradiol compound cream and tricyclic antidepressant nortriptyline pill
Drug: 5% lidocaine/5 mg/ml 0.02% estradiol compound cream · Drug: Nortriptyline
placebo cream and placebo pill
Drug: Placebo cream · Drug: Placebo pill
Lidocaine/estradiol cream targets peripheral nerves and tissues affected in VBD. Participants will be provided with a diagram and written instructions, detailing how to apply the cream to the vaginal vestibule daily for weeks 1-16. Treatment with lidocaine/estradiol or placebo cream will be terminated at week 16 (end of month 4).
Nortriptyline is a centrally-acting tricyclic antidepressant that is FDA-approved for treatment of neuropathic pain. Dosing will begin with one 10 mg pill nightly for week 1, then two 10 mg pills nightly for week 2, three 10 mg pills nightly for week 3, four 10 mg pills nightly for week 4, and five for weeks 5 -16. Treatment with nortriptyline or placebo pill will be tapered off over weeks 16-18, decreasing the dose by 10 mg every 4 days. Participants will be provided with a list of drugs to avoid that are known to interact with nortriptyline.
The comparison treatment will be an identical-appearing placebo Moisturel™ cream
Also known as: Moisturel cream
The comparison treatment will be an identical-appearing placebo pill
Pain Score During the Tampon Test
The Tampon Test will provide a self-reported numeric rating scale of pain with self-tampon insertion, performed by the patient and reported to the research nurse. Participants will be asked to verbally rate the pain on a scale of 0-10, with 0 meaning no pain and 10 meaning the worst possible pain.
Time frame: Baseline, 16 weeks
Change in Self-reported Pain Via the Short Form- McGill Pain Questionnaire (SF-MPQ)
The SF-MPQ consists of 15 descriptors which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. The total score ranges from 0 to 45, where a higher score indicates greater pain. A negative change score indicates a decrease in pain over time.
Time frame: Baseline, 16 weeks
Self-reported Physical Health Via SF-12 Health Survey (SF12v2)
The SF-12 physical health score has a mean of 50 and a standard deviation of 10 in the general population. Scores above 50 indicate a better-than-average health-related quality of life, while scores below 50 suggest below-average health.
Time frame: Prior to randomization
Self-reported Mental Health Via SF-12 Health Survey (SF12v2)
The SF-12 mental health score has a mean of 50 and a standard deviation of 10 in the general population. Scores above 50 indicate a better-than-average health-related quality of life, while scores below 50 suggest below-average health.
Time frame: Prior to randomization
Sexual Health Via Patient-Reported Outcomes Measurement Information System (PROMIS)
The PROMIS score is based on a 96-item form developed by the NIH that measures 11 domains of biopsychosocial function and includes an assessment of sexual function measures (e.g., desire, frequency, fear, and pain) related to sexual intercourse. The PROMIS Sexual Function and Satisfaction (SexFS) measures produce a T-score that summarizes a person's sexual health. The T-score is a standardized score that ranges from 0 to 100, where 50 indicates the population mean with a standard deviation of 10. Higher scores indicate greater satisfaction.
Time frame: Baseline, 16 weeks
Change in Pain Level as Measured by Vaginal Vestibule Pressure Pain Intensities (PPI)
Vaginal Vestibule PPIs will be determined using a cotton swab applied to externally-accessed sites (at 10, 6, and 2 o'clock on the vestibule) for 1-2 seconds. Upon application of cotton swab at each site, participants will rate their pain intensity on a scale from 0-10, where 0 = no pain and 10 = the worst pain possible. Reported as a composite mean score.
Time frame: Baseline, 8 weeks, and 16 weeks
Change in Levator Muscle Complex Pressure Pain Threshold (PPT)
Levator Muscle Complex PPTs will be determined using a digital vestibular algometer applied internally to the left puborectalis levator muscles site (7 o'clock) just lateral to the perineum. The test determines the amount of pressure over a given area in which a steadily increasing nonpainful pressure stimulus turns into a painful pressure sensation.
Time frame: Baseline, 16 weeks
Change in Pain Level as Measured by Remote Bodily PPTs
Remote Bodily PPTs will be determined by applying the algometer to 3 'neutral' non-pelvic body sites (deltoid, shin, and trapezius), right and left, beginning at 1N and increasing until the participant's first sensation of pain. PPT scores are rated on a scale of 0-10, where 0 meaning no pain and 10 meaning the worst pain possible. Reported as a composite mean score.
Time frame: Baseline, 8 weeks, and 16 weeks
Somatic Awareness Via Pennebaker Index of Limbic Languidness (PILL)
Pennebaker Index of Limbic Languidness (PILL) is used to create a summary score of somatic symptoms (e.g., itchy eyes, dizziness). Symptom frequency is recorded on a five-point Likert scale ranging from "never" (0) to "more than once a week" (4). The total score ranges from 0 to 216, where greater scores indicate greater frequency of symptoms.
Time frame: Baseline, 8 weeks, and 16 weeks
Change in Sleep as Measured by the Sleep Scale
The sleep scale is a 12-item scale that measures amount of sleep and ease/difficulty of initiating and maintaining sleep.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Perceived Stress Via Perceived Stress Scale (PSS)
The Perceived stress scale (PSS) is a 10-item scale that measures the impact of personal stress on thoughts and feelings.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Mood as Measured by the Symptom Checklist-27 (SCL-27)
Symptom Check List 27 (SCL-27) questionnaire will be used to measure a broad range of psychological symptoms (e.g., anxiety and depression).
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Inflammation as Measured by Cytokine Expression Levels
Cytokine expression levels will be measured via mesoscale discovery assays.
Time frame: Baseline, 16 weeks
Change in Cytokine Biomarkers at Other Time Points
Change in cytokine levels will be measured as described above.
Time frame: 8 weeks and 24 weeks
Change in microRNA Biomarkers at Other Time Points
Change in microRNA levels will be measured as described above.
Time frame: 8 weeks and 24 weeks
Change in Regulators of Pro-pain and Pro-inflammatory Genes, as Measured by microRNA Expression Levels
MicroRNA expression levels will be measured via sequencing read.
Time frame: Baseline, 16 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Headaches
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Widespread Pain
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Orofacial Pain
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Back Pain
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Abdominal Pain
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Bladder Pain
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Menstrual Pain
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
Change in Degree of Overlapping Pain, as Measured by COPC (Chronic Overlapping Pain Condition) Survey - Fatigue
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks
| Milestone | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Started | 52 | 52 | 52 | 53 |
| Completed | 40 | 34 | 47 | 45 |
| Not completed | 12 | 18 | 5 | 8 |
The Tampon Test will provide a self-reported numeric rating scale of pain with self-tampon insertion, performed by the patient and reported to the research nurse. Participants will be asked to verbally rate the pain on a scale of 0-10, with 0 meaning no pain and 10 meaning the worst possible pain.
| score on a scale | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline | 4.37 ± 0.30 | 3.75 ± 0.29 | 4.04 ± 0.36 | 4.36 ± 0.25 |
| 16 weeks | 3.02 ± 0.33 | 2.66 ± 0.36 | 3.22 ± 0.41 | 3.64 ± 0.39 |
The SF-MPQ consists of 15 descriptors which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. The total score ranges from 0 to 45, where a higher score indicates greater pain. A negative change score indicates a decrease in pain over time.
| score on a scale | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Change in Self-reported Pain Via the Short Form- McGill Pain Questionnaire (SF-MPQ) | -5.17 ± 1.05 | -5.08 ± 0.97 | -4.80 ± 0.85 | -4.60 ± 1.39 |
The SF-12 physical health score has a mean of 50 and a standard deviation of 10 in the general population. Scores above 50 indicate a better-than-average health-related quality of life, while scores below 50 suggest below-average health.
| score on a scale | Vestibulodynia (VBD) Peripheral | Vestibulodynia (VBD) Central |
|---|---|---|
| Self-reported Physical Health Via SF-12 Health Survey (SF12v2) | 55.05 ± 0.79 | 49.18 ± 0.77 |
The SF-12 mental health score has a mean of 50 and a standard deviation of 10 in the general population. Scores above 50 indicate a better-than-average health-related quality of life, while scores below 50 suggest below-average health.
| score on a scale | Vestibulodynia (VBD) Peripheral | Vestibulodynia (VBD) Central |
|---|---|---|
| Self-reported Mental Health Via SF-12 Health Survey (SF12v2) | 36.93 ± 1.12 | 36.54 ± 0.81 |
The PROMIS score is based on a 96-item form developed by the NIH that measures 11 domains of biopsychosocial function and includes an assessment of sexual function measures (e.g., desire, frequency, fear, and pain) related to sexual intercourse. The PROMIS Sexual Function and Satisfaction (SexFS) measures produce a T-score that summarizes a person's sexual health. The T-score is a standardized score that ranges from 0 to 100, where 50 indicates the population mean with a standard deviation of 10. Higher scores indicate greater satisfaction.
| score on a scale | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline | 40.64 ± 1.06 | 41.22 ± 0.82 | 41.67 ± 1.07 | 41.93 ± 1.07 |
| Week 16 | 44.36 ± 1.22 | 45.64 ± 1.28 | 42.92 ± 1.02 | 43.87 ± 1.06 |
Vaginal Vestibule PPIs will be determined using a cotton swab applied to externally-accessed sites (at 10, 6, and 2 o'clock on the vestibule) for 1-2 seconds. Upon application of cotton swab at each site, participants will rate their pain intensity on a scale from 0-10, where 0 = no pain and 10 = the worst pain possible. Reported as a composite mean score.
| score on a scale | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to 8 weeks | -0.37 ± 1.07 | -2.43 ± 1.11 | -0.57 ± 0.76 | -0.67 ± 0.95 |
| Baseline to 16 weeks | -2.14 ± 1.06 | -1.48 ± 1.10 | -2.33 ± 0.81 | -3.63 ± 1.03 |
Levator Muscle Complex PPTs will be determined using a digital vestibular algometer applied internally to the left puborectalis levator muscles site (7 o'clock) just lateral to the perineum. The test determines the amount of pressure over a given area in which a steadily increasing nonpainful pressure stimulus turns into a painful pressure sensation.
| kPa | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Change in Levator Muscle Complex Pressure Pain Threshold (PPT) | 3.16 ± 7.87 | -69.57 ± 51.32 | 0.45 ± 6.26 | -5.38 ± 22.54 |
Remote Bodily PPTs will be determined by applying the algometer to 3 'neutral' non-pelvic body sites (deltoid, shin, and trapezius), right and left, beginning at 1N and increasing until the participant's first sensation of pain. PPT scores are rated on a scale of 0-10, where 0 meaning no pain and 10 meaning the worst pain possible. Reported as a composite mean score.
| score on a scale | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to week 8 | 0.00 ± 0.99 | 0.21 ± 1.83 | -1.44 ± 1.37 | 0.28 ± 1.05 |
| Baseline to week 16 | -2.32 ± 0.89 | -0.35 ± 2.23 | -0.62 ± 2.11 | 1.00 ± 1.28 |
Pennebaker Index of Limbic Languidness (PILL) is used to create a summary score of somatic symptoms (e.g., itchy eyes, dizziness). Symptom frequency is recorded on a five-point Likert scale ranging from "never" (0) to "more than once a week" (4). The total score ranges from 0 to 216, where greater scores indicate greater frequency of symptoms.
| score on a scale | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline | 45.31 ± 2.79 | 45.63 ± 3.36 | 38.42 ± 2.82 | 42.55 ± 3.07 |
| Week 8 | 5.88 ± 3.03 | 1.96 ± 1.38 | 2.94 ± 1.78 | 4.75 ± 2.87 |
| Week 16 | 8.37 ± 4.16 | 5.46 ± 2.45 | 5.59 ± 2.40 | 7.66 ± 3.23 |
The sleep scale is a 12-item scale that measures amount of sleep and ease/difficulty of initiating and maintaining sleep.
No measurements were reported for this outcome.
The Perceived stress scale (PSS) is a 10-item scale that measures the impact of personal stress on thoughts and feelings.
No measurements were reported for this outcome.
Symptom Check List 27 (SCL-27) questionnaire will be used to measure a broad range of psychological symptoms (e.g., anxiety and depression).
No measurements were reported for this outcome.
Cytokine expression levels will be measured via mesoscale discovery assays.
Results for this outcome have not been posted.
Change in cytokine levels will be measured as described above.
Results for this outcome have not been posted.
Change in microRNA levels will be measured as described above.
Results for this outcome have not been posted.
MicroRNA expression levels will be measured via sequencing read.
Results for this outcome have not been posted.
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — Moderately Worse | 1 | 0 | 0 | 0 |
| Baseline to Week 8 — A Little Worse | 0 | 0 | 0 | 1 |
| Baseline to Week 8 — No Change | 3 | 3 | 2 | 4 |
| Baseline to Week 8 — A Little Better | 0 | 2 | 1 | 1 |
| Baseline to Week 8 — Moderately Better | 1 | 0 | 0 | 1 |
| Baseline to Week 8 — A Great Deal Better | 1 | 0 | 1 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — Moderately Worse | 0 | 0 | 0 | 1 |
| Week 8 to Week 16 — A Little Worse | 1 | 0 | 0 | 0 |
| Week 8 to Week 16 — No Change | 3 | 2 | 3 | 4 |
| Week 8 to Week 16 — A Little Better | 1 | 3 | 0 | 1 |
| Week 8 to Week 16 — Moderately Better | 1 | 0 | 1 | 0 |
| Week 8 to Week 16 — A Great Deal Better | 0 | 0 | 0 | 1 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — Moderately Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Little Worse | 1 | 0 | 1 | 0 |
| Week 16 to Week 24 — No Change | 2 | 2 | 3 | 4 |
| Week 16 to Week 24 — A Little Better | 2 | 0 | 0 | 2 |
| Week 16 to Week 24 — Moderately Better | 0 | 1 | 0 | 1 |
| Week 16 to Week 24 — A Great Deal Better | 1 | 1 | 0 | 0 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — Moderately Worse | 0 | 1 | 0 | 1 |
| Baseline to Week 8 — A Little Worse | 2 | 1 | 0 | 1 |
| Baseline to Week 8 — No Change | 8 | 7 | 10 | 9 |
| Baseline to Week 8 — A Little Better | 6 | 5 | 3 | 2 |
| Baseline to Week 8 — Moderately Better | 5 | 1 | 3 | 1 |
| Baseline to Week 8 — A Great Deal Better | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | 1 |
| Week 8 to Week 16 — Moderately Worse | 1 | 0 | 0 | 1 |
| Week 8 to Week 16 — A Little Worse | 0 | 0 | 1 | 2 |
| Week 8 to Week 16 — No Change | 6 | 3 | 7 | 4 |
| Week 8 to Week 16 — A Little Better | 4 | 6 | 4 | 4 |
| Week 8 to Week 16 — Moderately Better | 4 | 4 | 2 | 1 |
| Week 8 to Week 16 — A Great Deal Better | 3 | 0 | 1 | 1 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — Moderately Worse | 0 | 0 | 1 | 0 |
| Week 16 to Week 24 — A Little Worse | 1 | 0 | 0 | 1 |
| Week 16 to Week 24 — No Change | 7 | 4 | 8 | 8 |
| Week 16 to Week 24 — A Little Better | 4 | 3 | 3 | 3 |
| Week 16 to Week 24 — Moderately Better | 2 | 1 | 2 | 0 |
| Week 16 to Week 24 — A Great Deal Better | 3 | 3 | 1 | 2 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — Moderately Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — A Little Worse | 4 | 0 | 0 | 0 |
| Baseline to Week 8 — No Change | 1 | 3 | 5 | 4 |
| Baseline to Week 8 — A Little Better | 1 | 0 | 1 | 1 |
| Baseline to Week 8 — Moderately Better | 1 | 0 | 0 | 0 |
| Baseline to Week 8 — A Great Deal Better | 0 | 0 | 1 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | 1 |
| Week 8 to Week 16 — Moderately Worse | 2 | 0 | 2 | 1 |
| Week 8 to Week 16 — A Little Worse | 1 | 0 | 0 | 0 |
| Week 8 to Week 16 — No Change | 3 | 2 | 4 | 2 |
| Week 8 to Week 16 — A Little Better | 1 | 0 | 1 | 0 |
| Week 8 to Week 16 — Moderately Better | 0 | 1 | 0 | 0 |
| Week 8 to Week 16 — A Great Deal Better | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — Moderately Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Little Worse | 1 | 0 | 1 | 1 |
| Week 16 to Week 24 — No Change | 3 | 1 | 4 | 2 |
| Week 16 to Week 24 — A Little Better | 0 | 1 | 1 | 1 |
| Week 16 to Week 24 — Moderately Better | 1 | 0 | 1 | 0 |
| Week 16 to Week 24 — A Great Deal Better | 2 | 0 | 0 | 0 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — Moderately Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — A Little Worse | 4 | 3 | 2 | 1 |
| Baseline to Week 8 — No Change | 2 | 3 | 6 | 8 |
| Baseline to Week 8 — A Little Better | 1 | 6 | 1 | 0 |
| Baseline to Week 8 — Moderately Better | 1 | 0 | 3 | 0 |
| Baseline to Week 8 — A Great Deal Better | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | 1 |
| Week 8 to Week 16 — Moderately Worse | 2 | 0 | 1 | 0 |
| Week 8 to Week 16 — A Little Worse | 0 | 2 | 1 | 0 |
| Week 8 to Week 16 — No Change | 3 | 4 | 6 | 7 |
| Week 8 to Week 16 — A Little Better | 3 | 2 | 2 | 0 |
| Week 8 to Week 16 — Moderately Better | 0 | 0 | 2 | 0 |
| Week 8 to Week 16 — A Great Deal Better | 0 | 2 | 0 | 0 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — Moderately Worse | 0 | 0 | 1 | 0 |
| Week 16 to Week 24 — A Little Worse | 2 | 1 | 1 | 2 |
| Week 16 to Week 24 — No Change | 4 | 3 | 2 | 6 |
| Week 16 to Week 24 — A Little Better | 1 | 2 | 4 | 0 |
| Week 16 to Week 24 — Moderately Better | 1 | 0 | 2 | 0 |
| Week 16 to Week 24 — A Great Deal Better | 0 | 1 | 1 | 0 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — Moderately Worse | 0 | 0 | 1 | 2 |
| Baseline to Week 8 — A Little Worse | 0 | 0 | 0 | 1 |
| Baseline to Week 8 — No Change | 2 | 3 | 4 | 4 |
| Baseline to Week 8 — A Little Better | 4 | 2 | 2 | 0 |
| Baseline to Week 8 — Moderately Better | 1 | 1 | 2 | 0 |
| Baseline to Week 8 — A Great Deal Better | 1 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | 1 |
| Week 8 to Week 16 — Moderately Worse | 1 | 0 | 1 | 1 |
| Week 8 to Week 16 — A Little Worse | 1 | 0 | 1 | 1 |
| Week 8 to Week 16 — No Change | 3 | 2 | 4 | 3 |
| Week 8 to Week 16 — A Little Better | 3 | 3 | 0 | 1 |
| Week 8 to Week 16 — Moderately Better | 1 | 1 | 1 | 0 |
| Week 8 to Week 16 — A Great Deal Better | 0 | 0 | 2 | 0 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — Moderately Worse | 1 | 0 | 1 | 1 |
| Week 16 to Week 24 — A Little Worse | 2 | 0 | 4 | 1 |
| Week 16 to Week 24 — No Change | 2 | 2 | 2 | 5 |
| Week 16 to Week 24 — A Little Better | 1 | 2 | 1 | 0 |
| Week 16 to Week 24 — Moderately Better | 2 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Great Deal Better | 0 | 0 | 0 | 0 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — Moderately Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — A Little Worse | 0 | 1 | 0 | 0 |
| Baseline to Week 8 — No Change | 2 | 0 | 2 | 2 |
| Baseline to Week 8 — A Little Better | 1 | 0 | 2 | 1 |
| Baseline to Week 8 — Moderately Better | 1 | 1 | 1 | 0 |
| Baseline to Week 8 — A Great Deal Better | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — Moderately Worse | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Little Worse | 0 | 0 | 0 | 1 |
| Week 8 to Week 16 — No Change | 2 | 0 | 3 | 1 |
| Week 8 to Week 16 — A Little Better | 1 | 2 | 0 | 0 |
| Week 8 to Week 16 — Moderately Better | 0 | 0 | 1 | 1 |
| Week 8 to Week 16 — A Great Deal Better | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — Moderately Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Little Worse | 0 | 0 | 0 | 0 |
| Week 16 to Week 24 — No Change | 1 | 0 | 3 | 2 |
| Week 16 to Week 24 — A Little Better | 1 | 2 | 1 | 1 |
| Week 16 to Week 24 — Moderately Better | 1 | 0 | 0 | 0 |
| Week 16 to Week 24 — A Great Deal Better | 0 | 0 | 0 | 0 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | 1 |
| Baseline to Week 8 — Moderately Worse | 0 | 0 | 0 | 0 |
| Baseline to Week 8 — A Little Worse | 1 | 2 | 1 | 0 |
| Baseline to Week 8 — No Change | 7 | 5 | 5 | 11 |
| Baseline to Week 8 — A Little Better | 4 | 1 | 3 | 1 |
| Baseline to Week 8 — Moderately Better | 3 | 0 | 2 | 1 |
| Baseline to Week 8 — A Great Deal Better | 0 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Great Deal Worse | 1 | 0 | 0 | 1 |
| Week 8 to Week 16 — Moderately Worse | 1 | 0 | 0 | 0 |
| Week 8 to Week 16 — A Little Worse | 4 | 0 | 2 | 1 |
| Week 8 to Week 16 — No Change | 7 | 4 | 5 | 8 |
| Week 8 to Week 16 — A Little Better | 1 | 2 | 1 | 3 |
| Week 8 to Week 16 — Moderately Better | 1 | 0 | 1 | 0 |
| Week 8 to Week 16 — A Great Deal Better | 0 | 0 | 2 | 0 |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | 1 |
| Week 16 to Week 24 — Moderately Worse | 2 | 0 | 1 | 0 |
| Week 16 to Week 24 — A Little Worse | 0 | 0 | 1 | 2 |
| Week 16 to Week 24 — No Change | 9 | 4 | 6 | 8 |
| Week 16 to Week 24 — A Little Better | 2 | 2 | 0 | 1 |
| Week 16 to Week 24 — Moderately Better | 1 | 0 | 2 | 1 |
| Week 16 to Week 24 — A Great Deal Better | 0 | 0 | 0 | 0 |
Participants reported the change from previous timepoint in the degree of overlapping pain. Response options were: A Great Deal Worse, Moderately Worse, A Little Worse, No Change, A Little Better, Moderately Better, or A Great Deal Better.
| Participants | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| Baseline to Week 8 — A Great Deal Worse | 0 | 0 | 0 | — |
| Baseline to Week 8 — Moderately Worse | 0 | 1 | 0 | — |
| Baseline to Week 8 — A Little Worse | 0 | 0 | 0 | — |
| Baseline to Week 8 — No Change | 0 | 0 | 0 | — |
| Baseline to Week 8 — A Little Better | 0 | 0 | 0 | — |
| Baseline to Week 8 — Moderately Better | 0 | 1 | 1 | — |
| Baseline to Week 8 — A Great Deal Better | 1 | 0 | 0 | — |
| Week 8 to Week 16 — A Great Deal Worse | 0 | 0 | 0 | — |
| Week 8 to Week 16 — Moderately Worse | 1 | 0 | 0 | — |
| Week 8 to Week 16 — A Little Worse | 0 | 1 | 0 | — |
| Week 8 to Week 16 — No Change | 0 | 0 | 1 | — |
| Week 8 to Week 16 — A Little Better | 0 | 1 | 0 | — |
| Week 8 to Week 16 — Moderately Better | 0 | 0 | 0 | — |
| Week 8 to Week 16 — A Great Deal Better | 0 | 0 | 0 | — |
| Week 16 to Week 24 — A Great Deal Worse | 0 | 0 | 0 | — |
| Week 16 to Week 24 — Moderately Worse | 0 | 0 | 0 | — |
| Week 16 to Week 24 — A Little Worse | 0 | 0 | 0 | — |
| Week 16 to Week 24 — No Change | 1 | 1 | 0 | — |
| Week 16 to Week 24 — A Little Better | 0 | 0 | 1 | — |
| Week 16 to Week 24 — Moderately Better | 0 | 0 | 0 | — |
| Week 16 to Week 24 — A Great Deal Better | 0 | 1 | 0 | — |
Collected over 24 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Combined Peripheral and Central Treatments | 0/52 (0%) | 1/52 (1.9%) | 32/52 (61.5%) |
| Peripheral Treatment | 0/52 (0%) | 0/52 (0%) | 19/52 (36.5%) |
| Central Treatment | 0/52 (0%) | 1/52 (1.9%) | 33/52 (63.5%) |
| Placebo | 0/53 (0%) | 0/53 (0%) | 27/53 (50.9%) |
| Event | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| SeizureNervous system disorders | 0/52 | 0/52 | 1/52 | 0/53 |
| Severe Acute PancreatitisEndocrine disorders | 1/52 | 0/52 | 0/52 | 0/53 |
| Event | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo |
|---|---|---|---|---|
| OtherGeneral disorders | 20/52 | 12/52 | 19/52 | 14/53 |
| ConstipationGastrointestinal disorders | 7/52 | 1/52 | 11/52 | 1/53 |
| DrowsinessGeneral disorders | 5/52 | 4/52 | 10/52 | 4/53 |
| HeadachesGeneral disorders | 3/52 | 2/52 | 4/52 | 5/53 |
| Dry MouthGeneral disorders | 4/52 | 2/52 | 3/52 | 4/53 |
| NauseaGastrointestinal disorders | 3/52 | 4/52 | 2/52 | 2/53 |
| Weight GainGeneral disorders | 1/52 | 0/52 | 4/52 | 0/53 |
| Increased Heart RateCardiac disorders | 3/52 | 0/52 | 4/52 | 0/53 |
| DizzinessGeneral disorders | 4/52 | 1/52 | 0/52 | 3/53 |
| AnxietyPsychiatric disorders | 2/52 | 2/52 | 3/52 | 2/53 |
| Age, Continuous(years) | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo | Total |
|---|---|---|---|---|---|
| Mean | 27.2 ± 7.61 | 27.7 ± 7.74 | 26.5 ± 6.92 | 24.7 ± 6.48 | 26.5 ± 7.24 |
| Sex: Female, Male(Participants) | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo | Total |
|---|---|---|---|---|---|
| Female | 52 | 52 | 52 | 53 | 209 |
| Male | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 6 | 7 | 7 | 7 | 27 |
| Not Hispanic or Latino | 46 | 45 | 45 | 46 | 182 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 9 | 6 | 10 | 8 | 33 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 6 | 2 | 6 | 3 | 17 |
| White | 33 | 36 | 29 | 38 | 136 |
| More than one race | 4 | 8 | 7 | 4 | 23 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo | Total |
|---|---|---|---|---|---|
| United States | 52 | 52 | 52 | 53 | 209 |
| Vestibulodynia Subtype(Participants) | Combined Peripheral and Central Treatments | Peripheral Treatment | Central Treatment | Placebo | Total |
|---|---|---|---|---|---|
| Central | 38 | 33 | 37 | 33 | 141 |
| Peripheral | 14 | 19 | 15 | 20 | 68 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — The investigators will share data in a manner consistent with NIH's policy NOT-OD-14-124, found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html, released August 28, 2014. Genotypic data (e.g. microRNA and protein expression) and relevant phenotypic data (e.g. pain scores) from 400 participants will be posted on the dbGaP website.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: The PI expects data release up to 6 months after data submission is initiated or at the time of acceptance of initial publication, whichever occurs first.
Access criteria: Requests to download individual unit-record datasets should be submitted to the PI and require approval from a Data Access Committee convened by the NIH/NICHD.
Data sharing details ↗ · grants.nih.gov
Ran from Nov 2019 to primary completion in Mar 2024, 52 months.
Results were first posted in Mar 2026, 2 years after primary completion.
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Studies of the drug tested here: Nortriptyline