Dysmenorrhea (Disorder)Phase 4MCUPNCT04145518
Mechanistic Characterization of Uterine Pain
A Phase 4 study testing Naproxen Sodium in people with Dysmenorrhea (Disorder) and Dysmenorrhea Primary, run by Endeavor Health at 1 site in United States.
Trial summary
There are limited treatment options for management of dysmenorrhea, and the physiological processes they affect are not completely understood. For example, NSAIDs are effective in reducing menstrual pain in some women by inhibition of prostaglandin synthesis, but whether those effects are mediated by affecting… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Dysmenorrhea (Disorder), Dysmenorrhea Primary, Dysmenorrhea Secondary
- What is being tested?
- Naproxen Sodium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 183 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2019to 23 Jul 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Inclusion Criteria for Primary Dysmenorrhea Group: All cases (n=70) will have pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament, and rate their average pain greater than or equal to 6/10 (0 = no pain; 10 = worst imaginable pain) during menses when not using NSAIDs. The investigators will use strict inclusion criteria and verification with structural MRI to ensure patients with primary dysmenorrhea most likely do not have endometriosis, leiomyoma, or adenomyosis as described below. It is not possible to reliably evaluate superficial endometriosis with MRI (Nisenblat et al., 2016), but suspicious cases for deep infiltrating endometriosis will be confirmed by the radiologists who routinely evaluate MRIs for our gynecological surgical service. Although it is impossible to rule out endometriosis without surgery, in select cases The investigators will use clinical exams and criteria supported by decision trees (Eskenazi et al., 2001; Chapron et al., 2005, 2011; Vercellini et al., 2007) that suggest the detection of endometriosis stage 2 or higher would be unlikely (<15%) in this population. Participants with dysmenorrhea that rate their bowel pain, dyspareunia, or non-menstrual pelvic pain equal to or greater than 40 on 0-100 visual analog pain scale on the McGill Pain Questionnaire will be given the option to participate in an additional clinical exam visit. To reduce the likelihood of comorbid endometriosis, primary dysmenorrhea participants with symptoms of endometriosis described above, will be required to have a negative clinical exam and no immediate family history of endometriosis to qualify for final analyses.
- Inclusion Criteria for Leiomyomata Group: The investigators will also study participants with leiomyomata (n=20) because it is a frequent cause of menstrual pain and will often be identified in disqualified primary dysmenorrhea participants. Leiomyomata (nondegenerated) will be diagnosed by foci homogeneously hypointense on T2, but isointense relative to myometrium on T1 according to standard definitions (Kubik-Huch et al., 2018). To reduce variability within this category, the investigators will restrict enrollment to small to medium sized intramural leiomyomata (30 to 150 cm3 combined volume). The investigators anticipate 10 participants with leiomyomata will be identified from incidental MRI during this study, while 10 more will be recruited from advertisements and our clinic. A smaller cohort is studied here because the main purpose of this group is to establish whether the physiological basis for menstrual pain in women with leiomyomata is significantly different than women with primary dysmenorrhea. Participants with leiomyomata, who are also symptomatic with surgically diagnosed endometriosis will be excluded.
- Inclusion Criteria for Endometriosis Group: Participants without leiomyomata, but symptomatic for endometriosis (n=20) will be enrolled before planned surgical excision (follow-up surgery from an earlier diagnosis). The investigators will confirm a diagnosis of Stage 2, 3, or 4 endometriosis following surgery. For the patients without confirmed abnormal surgical findings for endometriosis with dysmenorrhea will be considered as primary dysmenorrhea cases. Dr. Tu's pelvic pain division performs over 100 laparoscopic pain evaluations annually (many with deep infiltrating disease) enabling us to characterize MRI signals in surgically confirmed endometriosis patients. A smaller cohort is studied here because the main purpose of this group is to establish whether the physiological basis for menstrual pain in women with endometriosis is significantly different than women with primary dysmenorrhea.
- Inclusion Criteria for Healthy Controls: Healthy control cases (n=20) must rate their average menstrual pain < =2/10 over that past 6 months (without NSAID use) and have no other concurrent pain diagnoses or leiomyomata. Their lack of concurrent pain diagnoses will be confirmed with questionnaires (NIH PROMIS scales, Rome Foundation IBS criteria (Palsson et al., 2016), AUA bladder pain syndrome criteria (Hanno et. al. 2012), and the Complex Medical Symptom Inventory (Williams and Schilling, 2009) and a medical exam screen. Healthy controls and participants with primary dysmenorrhea will be ratio-metrically age-matched with comparable pregnancy history to ensure similar demographics between groups.
Who cannot join
- Age restrictions for all study participants: Regularly menstruating women (age 18-45) will be identified using our well-tested community-wide recruitment strategy, including approaching our division's busy gynecological disorders clinic, and the departments of Ob/Gyn at NorthShore and the University of Chicago. Although women above the age of 45 can have menstrual pain, irregularities in perimenopause could cause confounding effects on uterine physiology and scheduling difficulty. Similarly, irregularities in menstruation, ovulation, and pain levels in participants under age 18 could potentially detract from meaningful interpretation of phenotypes (Seidman et al., 2018). Additionally, before age 18, the uterus is still developing and substantially increasing in size (Porcu et al., 1989; Verguts et al., 2013). Thus, to limit potential confounding effects, participants under the age of 18 will be investigated in a separate study.
- Menstruation-related exclusion criteria for all study participants: The investigators will exclude certain participants with conditions associated with the absence of regular menses such as polycystic ovarian syndrome, pregnancy, current use of any continuous hormonal medication or contraceptive, or Asherman's syndrome.
- MRI-related or participation related exclusion criteria for all study participants:
- The investigators will exclude participants with criteria that would affect our ability to obtaining meaningful MRI data such as
- presence of an intrauterine device (IUD). The use of an IUD potentially affects interpretability of MRI because it creates an imaging artifact in the endometrium extending to the myometrium.
- inability to read or comprehend the informed consent written in English,
Show all 27Show fewer
- history of metallic implants,
- history of metallic injury,
- any diagnosed condition that would preclude investigation with MRI (e.g., claustrophobia),
- BMI >40,
- allergy or inability to tolerate naproxen
- Exclusion criteria for known factors that affect the interpretability of the data for all study participants:
- thyroid dysfunction,
- adrenal dysfunction,
- renal disorders,
- liver disorders,
- coagulopathy,
- prolactinoma,
- von Willebrand disease,
- platelet disorders,
- diabetic neuropathy,
- gastrointestinal conditions or surgeries that would affect naproxen absorption,
- active genitourinary or sexually transmitted infection
- Provisional exclusion for primary analyses for all study participants: Acute or chronic conditions associated with pelvic pain with a defined anatomical cause other than endometriosis or leiomyoma (e.g., pathological ovarian cysts, significant persistent hydro/hematosalpinx, untreated pelvic inflammatory disease, active pelvic or abdominal malignancies, Mullerian anomalies, or stage 3 uterine prolapse), and comorbid diagnosis of significant leiomyoma and endometriosis.
- Note: these exclusion criteria may be incidentally discovered after the MRI scan and confirmed with a radiologist's or Dr. Tu's diagnosis.
- Provisional exclusion for adenomyosis group: Because the frequency of adenomyosis is low or unknown, and may consist of multiple subtypes resulting in heterogeneity and inadequate statistical power, adenomyosis patients are not a planned study group and diagnosed cases will be initially excluded from recruitment. Focal and diffuse adenomyosis will be excluded by guidelines (Chapron et al., 2017) adapted from the Kishi criteria (Kishi et al., 2012): maximal junctional zone thickness exceeding 12 mm, a ratio of junctional zone thickness to myometrium exceeding 40%, or high-intensity foci within the myometrium. If a substantial number of adenomyosis participants participate, as discovered after-the-fact with MRI, results will be analyzed.
- Intermediate levels of dysmenorrhea pain exclusion: Participants with mild menstrual pain (between 3 and 5 on a 0-10 scale) will be excluded. Our prior experience with this cohort (Westling et al., 2013) suggests that The investigators may encounter a floor effect when studying the effectiveness of NSAIDs. Also, since this cohort is most likely to respond to NSAIDs, it is imperative The investigators study the mechanisms of the most severe sufferers of refractory menstrual pain.
Trial locations and contacts
1 site in 1 country.
United States1 site
NorthShore University HealthSystem
Evanston, Illinois, 60201
About this study
Official title: Mechanistic Characterization of Uterine Pain (MCUP) to Improve Diagnosis and Treatment for Dysmenorrhea
There are limited treatment options for management of dysmenorrhea, and the physiological processes they affect are not completely understood. For example, NSAIDs are effective in reducing menstrual pain in some women by inhibition of prostaglandin synthesis, but whether those effects are mediated by affecting contractility, perfusion, or hypoxemia is unknown. Understanding how these drugs relieve menstrual pain (and why they fail) would be of substantial clinical significance. Given the foregoing, Two Specific Aims are proposed:
Aim #1: Characterize menstrual pain phenotypes associated with impairments in myometrial activity, perfusion, and/or oxygenation. Continuous MRI scans of the uterus will be performed with simultaneous measurement of self-reported pain in healthy women and those experiencing menstrual pain. The investigators will include cohorts of women with imaging diagnosed leiomyoma and surgically-confirmed endometriosis to evaluate the contribution of structurally identifiable factors. Based on preliminary data, the investigators anticipate finding four phenotypes with menstrual pain related to: 1) myometrial activity, 2) inadequate perfusion and/or oxygenation, 3) a combination of phenotypes 1 \& 2, and 4) a non-uterine source.
Read more
Aim #2: Evaluate the effects of naproxen on myometrial activity, perfusion, and/or oxygenation with respect to pain relief. In women with primary dysmenorrhea, the investigators will acquire pelvic MRI scans and evaluate self-reported menstrual cramping pain before and after administration of randomized naproxen or placebo.
Naproxen could principally affect one or more potential sources of uterine pain such as myometrial activity, perfusion, and/or oxygenation. The investigators will corroborate preliminary data findings, which suggest menstrual phenotypes with myometrial activity will be more likely to respond. Conversely, Aim 2 will also elucidate the mechanisms responsible for inadequate pain relief from naproxen.
Bioavailability of naproxen levels and other molecules associated with NSAID-resistance will be evaluated from the serum of participants after taking naproxen using HPLC-MS.
Read the detailed description
Due to a lack of noninvasive tools to study uterine physiology, the root causes of menstrual cramping pain within primary dysmenorrhea and secondary dysmenorrhea (leiomyoma, endometriosis, adenomyosis) remain unknown. This pain does not respond to typical over-the-counter anti-inflammatories in 15% of women and is a leading risk factor for developing challenging chronic pelvic pain disorders. In order to guide drug discoveries and create personalized treatment approaches, it is essential to unveil the underlying mechanisms of dysmenorrhea. Our research program has focused on key gaps in our knowledge of uterine physiology, such as the contributions of uterine contractions, perfusion, and oxygenation to menstrual pain. Although these factors are strongly implicated in this debilitating pain disorder, confirmatory human data is still needed. Such research would be quite timely, as numerous drug candidates targeting these potential mechanisms already exist. Our collaborative team has developed MRI-based tools to noninvasively and dynamically measure uterine contractions, perfusion, relative tissue oxygenation, and metabolites indicative of anaerobic respiration. The investigators have also pioneered methods that link spontaneous pain report to simultaneous uterine events. Together, these methods will allow us to evaluate the contribution of contractility, perfusion, or hypoxemia to menstrual pain. Notably, our preliminary data supports our central hypothesis that menstrual pain is associated with different phenotypes involving myometrial hypercontractility, impaired uterine perfusion, uterine hypoxemia, or a non-uterine source. Since understanding how current anti-inflammatory medications relieve or prevent pain (and why they fail) is valuable for the development of improved treatment strategies, the investigators will also investigate the effects of naproxen on uterine physiology in women with menstrual pain. To test our hypothesized contributions of altered uterine muscle activity, perfusion, and oxygenation on pain, The investigators propose: Aim 1: Characterize menstrual pain phenotypes associated with impairments in myometrial activity, perfusion, and/or oxygenation. Continuous MRI sequences of the uterus will be performed with simultaneous measurement of self-reported pain in healthy women and those experiencing menstrual pain. A cohort of women with leiomyoma and endometriosis will also be analyzed to evaluate the contribution of myometrial activity, perfusion, and oxygenation in women with structurally identifiable conditions. Aim 2: Evaluate the effects of naproxen on myometrial activity, perfusion, and/or oxygenation with respect to pain relief. Preliminary data suggests unresolved myometrial activity and inadequate naproxen absorption are associated with insufficient pain relief. Evaluating the naproxen-dependent effects of uterine physiology will provide a foundation for diagnostic tests to indicate relevant personalized treatment for patients that have failed conventional treatments. Further translation of these studies could advance mechanisms for discovery in other chronic pelvic pain conditions and uterine disorders such as idiopathic preterm labor and unexplained infertility.
- Conditions
- Dysmenorrhea (Disorder), Dysmenorrhea Primary, Dysmenorrhea Secondary, Endometrial Diseases, Leiomyoma, Fibroid Uterus
- Being tested
- Naproxen Sodium, Placebo
- Keywords
- pain, NSAID, women's health, uterus, MRI
- Medical subject headings
- Dysmenorrhea, Uterine Diseases, Leiomyoma, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naproxen SodiumDrug
Single oral dose of 550 mg naproxen sodium (equivalent to 500 mg naproxen base), given as one tablet identical in size, shape, and appearance to the matching placebo. Administered once during a menstrual MRI visit (within 48 hours of menses onset), immediately after the pre-treatment scan and approximately 90 minutes before the post-treatment scan. Each participant receives naproxen at only one of the two MRI visits; the alternate visit (1-2 months later) uses placebo, per the randomized, quadruple-masked crossover. 550 mg naproxen sodium is the highest FDA-approved starting dose; the sodium salt formulation is used to speed absorption.
PlaceboDrug
Single oral placebo pill containing no active drug, matched in size, shape, and appearance to the 550 mg naproxen sodium tablet and supplied in coded containers by the clinical research pharmacy. Administered once during a menstrual MRI visit on the same schedule as naproxen (immediately after the pre-treatment scan, approximately 90 minutes before the post-treatment scan). Each participant receives placebo at only one of the two MRI visits; the alternate visit uses naproxen, per the randomized, quadruple-masked crossover.
| Study group | Role | What they receive |
|---|---|---|
| Naproxen First, Then Placebo | Experimental | Participants randomized to this sequence take a single oral 550 mg naproxen sodium tablet at the first menstrual MRI visit and a matching placebo pill at the second MRI visit (a subsequent menstrual episode, 1-2 months later). At each visit the pill is taken immediately after the pre-treatment scan, approximately 90 minutes before the post-treatment scan. Allocation is quadruple-masked: assignment was randomized in REDCap using a block size known only to the study statistician, with naproxen and identical-appearing placebo dispensed in coded containers by the clinical research pharmacy. Receives: Drug: Naproxen Sodium; Drug: Placebo |
| Placebo First, Then Naproxen | Experimental | Participants randomized to this sequence take a matching placebo pill at the first menstrual MRI visit and a single oral 550 mg naproxen sodium tablet at the second MRI visit (a subsequent menstrual episode, 1-2 months later). Pill timing relative to the scans, blinding, randomization, and pharmacy dispensing are identical to the other sequence. Receives: Drug: Naproxen Sodium; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Concordant Phenotype Assignment at Both MRI Visits
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Each participant's two menstrual MRI scans were independently assigned to one of these phenotypes. A participant was counted as concordant if both scans were assigned to the same phenotype. Reported as the number and percentage of participants with concordant assignment.
Measured: Two menstrual MRI visits separated by 1 to 2 menstrual cycles (approximately 4 to 8 weeks).
Frequency of Uterine Contractions and BOLD Oxygenation-desaturation Events by Menstrual Pain Phenotype
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). This measure reports the mean number of uterine contractions and BOLD oxygenation-desaturation events detected per 10-minute scan within each phenotype. R2* and arterial spin labeling sequences were not acquired in this round and were not included in phenotyping.
Measured: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Mean Duration of Individual Uterine Contractions by Menstrual Pain Phenotype
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). This measure reports the mean duration of an individual uterine contraction within each phenotype. Duration was quantified as the number of HASTE frames spanning each contraction, acquired at 2 frames per second, and is reported here in seconds. Longer values indicate contractions of greater individual duration.
Measured: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Myometrial and Junctional Zone Thickness by Menstrual Pain Phenotype
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). This measure reports mean myometrial and junctional zone thickness, measured in millimetres at the anterior and posterior uterine wall, within each phenotype.
Measured: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
BOLD Signal Intensity and Desaturation Dip Magnitude by Menstrual Pain Phenotype
Phenotypes were derived post hoc by principal component analysis and Ward hierarchical clustering of eleven HASTE and BOLD signal variables from the pre-dose menstrual MRI scan, at the scan level; each participant contributed up to two scans (84 participants, 119 scans). A desaturation event is a transient drop in BOLD signal. Baseline signal intensity is the mean BOLD signal preceding a desaturation event; minimum signal intensity is the mean signal at the nadir of the event; range of signal change is the difference between them. Higher baseline and minimum values indicate greater BOLD signal, and a larger range indicates a deeper desaturation, i.e. a greater transient drop in oxygenation. Scans with no desaturation event were assigned a nadir equal to baseline and a range of zero. Values are in arbitrary scanner signal intensity units and are not comparable across studies.
Measured: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Percentage Change in BOLD Signal From Baseline by Menstrual Pain Phenotype
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). Percentage signal change expresses the magnitude of the BOLD desaturation as a proportion of baseline signal intensity, so larger values indicate a deeper transient drop in oxygenation. It is defined only where a desaturation event was detected; scans without a detected event were assigned a value of zero. Phenotype P2 was characterized by near-absent BOLD activity, so its distribution consists predominantly of these structural zeros.
Measured: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Change in Junctional Zone Thickness From Pre-dose to Post-dose Scan, Naproxen Versus Placebo
Within-subject change in junctional zone thickness, measured in millimetres, from the pre-dose to the post-dose scan, compared between the naproxen and placebo conditions in participants with primary dysmenorrhea. Change is calculated as post-dose minus pre-dose, so positive values indicate greater thickness after dosing. Each participant contributed a change score under both conditions. Row numbers analyzed differ because not every participant had both scans measurable at both wall locations. Post-dose BOLD sequences were successfully acquired at only 5 of 39 crossover visit pairs, and R2* and arterial spin labeling sequences were not acquired in this round, so no naproxen-versus-placebo comparison is reported for those signal families.
Measured: Pre-dose scan to post-dose scan at each of two menstrual MRI visits; the post-dose scan began approximately 90 minutes after dosing (each scan approximately 1 hour).
Change in Uterine Contraction Frequency From Pre-dose to Post-dose Scan, Naproxen Versus Placebo
Within-subject change in the number of uterine contractions detected per 10-minute scan, from the pre-dose to the post-dose scan, compared between the naproxen and placebo conditions in participants with primary dysmenorrhea. Change is calculated as post-dose minus pre-dose, so positive values indicate more contractions after dosing. Each participant contributed a change score under both conditions. Post-dose BOLD sequences were successfully acquired at only 5 of 39 crossover visit pairs, and R2* and arterial spin labeling sequences were not acquired in this round, so no naproxen-versus-placebo comparison is reported for those signal families.
Measured: Pre-dose scan to post-dose scan at each of two menstrual MRI visits; the post-dose scan began approximately 90 minutes after dosing (each scan approximately 1 hour).
Secondary outcomes (3)
Agreement Between Primary and Sensitivity Phenotype Clustering Solutions (Adjusted Rand Index)
Sensitivity analysis testing the stability of the three-phenotype clustering solution. Clustering was re-run after excluding participants reclassified on independent anatomical review, and the resulting partition was compared with the primary solution across the retained pre-dose MRI scans using the adjusted Rand index. The adjusted Rand index measures agreement between two partitions of the same data, corrected for chance: 1.0 indicates identical partitions, 0 indicates agreement no better than chance, and negative values indicate agreement worse than chance. The index is a single value describing agreement across the entire retained set of scans rather than a per-participant measurement, so one number is reported for the group as a whole and no comparison between arms is possible.
Measured: Two menstrual MRI visits separated by 1 to 2 menstrual cycles (approximately 4 to 8 weeks). Pre-dose scan at each visit assessed.
Correlation of NSAID Resistance With Clinical/Psychosocial Covariates
NSAID resistance was defined as pain intensity at 6 hours after naproxen dosing minus peak pre-dose pain intensity, each rated on a 0 to 10 Numerical Rating Scale, so that higher values indicate less pain relief. This measure reports the Spearman rank correlation between NSAID resistance and six covariates: age in years; parity, the number of prior deliveries; the Sexual and Physical Abuse Questionnaire total score, scored only where all seven items were completed; PROMIS Anxiety and PROMIS Depression short-form scores, reported as raw summed scores rather than standardized T-scores; and pressure-pain threshold, the mean force at which applied abdominal pressure was first reported as painful. A positive correlation indicates that higher covariate values are associated with less pain relief.
Measured: Peak pre-dose pain to 6 hours after naproxen dosing at the naproxen menstrual MRI visit.
Correlation of NSAID Resistance With Serum Naproxen (90 Min)
NSAID resistance was defined as pain intensity at 6 hours after naproxen dosing minus peak pre-dose pain intensity, each rated on a 0 to 10 Numerical Rating Scale, so that higher values indicate less pain relief. Serum naproxen concentration was measured from a blood sample drawn 90 minutes after dosing, at approximately the time of the post-dose scan. This measure reports the Spearman rank correlation between serum naproxen concentration and NSAID resistance, testing whether variation in drug absorption accounts for variation in pain relief. A negative correlation would indicate that higher serum concentrations are associated with greater pain relief.
Measured: Peak pre-dose pain to 6 hours after naproxen dosing at the naproxen menstrual MRI visit; serum was sampled 90 minutes after dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study start25 Oct 2019
- Primary completion23 Jul 2025
- Study completion23 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Dysmenorrhea (Disorder)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endeavor Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Kevin Hellman, Endeavor Health
- Investigators
- Kevin M Hellman, PhD, Principal investigator, Endeavor Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04145518
- Sponsor's protocol ID
- EH19-040
- Other IDs
- R01HD098193-01A1
- Acronym
- MCUP
- Status last verified
- Aug 2026
- First submitted
- 25 Oct 2019
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Characterization of Uterine Pain (MCUP) to Improve Diagnosis and Treatment for Dysmenorrhea
- ClinicalTrials.gov ID
- NCT04145518
- Acronym / sponsor ID
- MCUP / EH19-040
- Conditions
- Dysmenorrhea (Disorder), Dysmenorrhea Primary, Dysmenorrhea Secondary, Endometrial Diseases, Leiomyoma, Fibroid Uterus
- Keywords
- pain, NSAID, women's health, uterus, MRI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- Endeavor HealthUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 25 Oct 2019 (actual)
- Primary completion
- 23 Jul 2025 (actual)
- Study completion
- 23 Jul 2025 (actual)
- First posted
- 30 Oct 2019 (actual)
- Results
- Posted 23 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are limited treatment options for management of dysmenorrhea, and the physiological processes they affect are not completely understood. For example, NSAIDs are effective in reducing menstrual pain in some women by inhibition of prostaglandin synthesis, but whether those effects are mediated by affecting contractility, perfusion, or hypoxemia is unknown. Understanding how these drugs relieve menstrual pain (and why they fail) would be of substantial clinical significance. Given the foregoing, Two Specific Aims are proposed:
Aim #1: Characterize menstrual pain phenotypes associated with impairments in myometrial activity, perfusion, and/or oxygenation. Continuous MRI scans of the uterus will be performed with simultaneous measurement of self-reported pain in healthy women and those experiencing menstrual pain. The investigators will include cohorts of women with imaging diagnosed leiomyoma and surgically-confirmed endometriosis to evaluate the contribution of structurally identifiable factors. Based on preliminary data, the investigators anticipate finding four phenotypes with menstrual pain related to: 1) myometrial activity, 2) inadequate perfusion and/or oxygenation, 3) a combination of phenotypes 1 \& 2, and 4) a non-uterine source.
Aim #2: Evaluate the effects of naproxen on myometrial activity, perfusion, and/or oxygenation with respect to pain relief. In women with primary dysmenorrhea, the investigators will acquire pelvic MRI scans and evaluate self-reported menstrual cramping pain before and after administration of randomized naproxen or placebo.
Naproxen could principally affect one or more potential sources of uterine pain such as myometrial activity, perfusion, and/or oxygenation. The investigators will corroborate preliminary data findings, which suggest menstrual phenotypes with myometrial activity will be more likely to respond. Conversely, Aim 2 will also elucidate the mechanisms responsible for inadequate pain relief from naproxen.
Bioavailability of naproxen levels and other molecules associated with NSAID-resistance will be evaluated from the serum of participants after taking naproxen using HPLC-MS.
Detailed description
Due to a lack of noninvasive tools to study uterine physiology, the root causes of menstrual cramping pain within primary dysmenorrhea and secondary dysmenorrhea (leiomyoma, endometriosis, adenomyosis) remain unknown. This pain does not respond to typical over-the-counter anti-inflammatories in 15% of women and is a leading risk factor for developing challenging chronic pelvic pain disorders. In order to guide drug discoveries and create personalized treatment approaches, it is essential to unveil the underlying mechanisms of dysmenorrhea. Our research program has focused on key gaps in our knowledge of uterine physiology, such as the contributions of uterine contractions, perfusion, and oxygenation to menstrual pain. Although these factors are strongly implicated in this debilitating pain disorder, confirmatory human data is still needed. Such research would be quite timely, as numerous drug candidates targeting these potential mechanisms already exist. Our collaborative team has developed MRI-based tools to noninvasively and dynamically measure uterine contractions, perfusion, relative tissue oxygenation, and metabolites indicative of anaerobic respiration. The investigators have also pioneered methods that link spontaneous pain report to simultaneous uterine events. Together, these methods will allow us to evaluate the contribution of contractility, perfusion, or hypoxemia to menstrual pain. Notably, our preliminary data supports our central hypothesis that menstrual pain is associated with different phenotypes involving myometrial hypercontractility, impaired uterine perfusion, uterine hypoxemia, or a non-uterine source. Since understanding how current anti-inflammatory medications relieve or prevent pain (and why they fail) is valuable for the development of improved treatment strategies, the investigators will also investigate the effects of naproxen on uterine physiology in women with menstrual pain. To test our hypothesized contributions of altered uterine muscle activity, perfusion, and oxygenation on pain, The investigators propose: Aim 1: Characterize menstrual pain phenotypes associated with impairments in myometrial activity, perfusion, and/or oxygenation. Continuous MRI sequences of the uterus will be performed with simultaneous measurement of self-reported pain in healthy women and those experiencing menstrual pain. A cohort of women with leiomyoma and endometriosis will also be analyzed to evaluate the contribution of myometrial activity, perfusion, and oxygenation in women with structurally identifiable conditions. Aim 2: Evaluate the effects of naproxen on myometrial activity, perfusion, and/or oxygenation with respect to pain relief. Preliminary data suggests unresolved myometrial activity and inadequate naproxen absorption are associated with insufficient pain relief. Evaluating the naproxen-dependent effects of uterine physiology will provide a foundation for diagnostic tests to indicate relevant personalized treatment for patients that have failed conventional treatments. Further translation of these studies could advance mechanisms for discovery in other chronic pelvic pain conditions and uterine disorders such as idiopathic preterm labor and unexplained infertility.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naproxen First, Then Placebo | Experimental | Drug: Naproxen Sodium, Drug: PlaceboParticipants randomized to this sequence take a single oral 550 mg naproxen sodium tablet at the first menstrual MRI visit and a matching placebo pill at the second MRI visit (a subsequent menstrual episode, 1-2 months later). At each visit the pill is taken immediately after the pre-treatment scan, approximately 90 minutes before the post-treatment scan. Allocation is quadruple-masked: assignment was randomized in REDCap using a block size known only to the study statistician, with naproxen and identical-appearing placebo dispensed in coded containers by the clinical research pharmacy. |
| Placebo First, Then Naproxen | Experimental | Drug: Naproxen Sodium, Drug: PlaceboParticipants randomized to this sequence take a matching placebo pill at the first menstrual MRI visit and a single oral 550 mg naproxen sodium tablet at the second MRI visit (a subsequent menstrual episode, 1-2 months later). Pill timing relative to the scans, blinding, randomization, and pharmacy dispensing are identical to the other sequence. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Inclusion Criteria for Primary Dysmenorrhea Group: All cases (n=70) will have pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament, and rate their average pain greater than or equal to 6/10 (0 = no pain; 10 = worst imaginable pain) during menses when not using NSAIDs. The investigators will use strict inclusion criteria and verification with structural MRI to ensure patients with primary dysmenorrhea most likely do not have endometriosis, leiomyoma, or adenomyosis as described below. It is not possible to reliably evaluate superficial endometriosis with MRI (Nisenblat et al., 2016), but suspicious cases for deep infiltrating endometriosis will be confirmed by the radiologists who routinely evaluate MRIs for our gynecological surgical service. Although it is impossible to rule out endometriosis without surgery, in select cases The investigators will use clinical exams and criteria supported by decision trees (Eskenazi et al., 2001; Chapron et al., 2005, 2011; Vercellini et al., 2007) that suggest the detection of endometriosis stage 2 or higher would be unlikely (<15%) in this population. Participants with dysmenorrhea that rate their bowel pain, dyspareunia, or non-menstrual pelvic pain equal to or greater than 40 on 0-100 visual analog pain scale on the McGill Pain Questionnaire will be given the option to participate in an additional clinical exam visit. To reduce the likelihood of comorbid endometriosis, primary dysmenorrhea participants with symptoms of endometriosis described above, will be required to have a negative clinical exam and no immediate family history of endometriosis to qualify for final analyses.
- Inclusion Criteria for Leiomyomata Group: The investigators will also study participants with leiomyomata (n=20) because it is a frequent cause of menstrual pain and will often be identified in disqualified primary dysmenorrhea participants. Leiomyomata (nondegenerated) will be diagnosed by foci homogeneously hypointense on T2, but isointense relative to myometrium on T1 according to standard definitions (Kubik-Huch et al., 2018). To reduce variability within this category, the investigators will restrict enrollment to small to medium sized intramural leiomyomata (30 to 150 cm3 combined volume). The investigators anticipate 10 participants with leiomyomata will be identified from incidental MRI during this study, while 10 more will be recruited from advertisements and our clinic. A smaller cohort is studied here because the main purpose of this group is to establish whether the physiological basis for menstrual pain in women with leiomyomata is significantly different than women with primary dysmenorrhea. Participants with leiomyomata, who are also symptomatic with surgically diagnosed endometriosis will be excluded.
- Inclusion Criteria for Endometriosis Group: Participants without leiomyomata, but symptomatic for endometriosis (n=20) will be enrolled before planned surgical excision (follow-up surgery from an earlier diagnosis). The investigators will confirm a diagnosis of Stage 2, 3, or 4 endometriosis following surgery. For the patients without confirmed abnormal surgical findings for endometriosis with dysmenorrhea will be considered as primary dysmenorrhea cases. Dr. Tu's pelvic pain division performs over 100 laparoscopic pain evaluations annually (many with deep infiltrating disease) enabling us to characterize MRI signals in surgically confirmed endometriosis patients. A smaller cohort is studied here because the main purpose of this group is to establish whether the physiological basis for menstrual pain in women with endometriosis is significantly different than women with primary dysmenorrhea.
- Inclusion Criteria for Healthy Controls: Healthy control cases (n=20) must rate their average menstrual pain < =2/10 over that past 6 months (without NSAID use) and have no other concurrent pain diagnoses or leiomyomata. Their lack of concurrent pain diagnoses will be confirmed with questionnaires (NIH PROMIS scales, Rome Foundation IBS criteria (Palsson et al., 2016), AUA bladder pain syndrome criteria (Hanno et. al. 2012), and the Complex Medical Symptom Inventory (Williams and Schilling, 2009) and a medical exam screen. Healthy controls and participants with primary dysmenorrhea will be ratio-metrically age-matched with comparable pregnancy history to ensure similar demographics between groups.
Key exclusion criteria (27 listed)
- Age restrictions for all study participants: Regularly menstruating women (age 18-45) will be identified using our well-tested community-wide recruitment strategy, including approaching our division's busy gynecological disorders clinic, and the departments of Ob/Gyn at NorthShore and the University of Chicago. Although women above the age of 45 can have menstrual pain, irregularities in perimenopause could cause confounding effects on uterine physiology and scheduling difficulty. Similarly, irregularities in menstruation, ovulation, and pain levels in participants under age 18 could potentially detract from meaningful interpretation of phenotypes (Seidman et al., 2018). Additionally, before age 18, the uterus is still developing and substantially increasing in size (Porcu et al., 1989; Verguts et al., 2013). Thus, to limit potential confounding effects, participants under the age of 18 will be investigated in a separate study.
- Menstruation-related exclusion criteria for all study participants: The investigators will exclude certain participants with conditions associated with the absence of regular menses such as polycystic ovarian syndrome, pregnancy, current use of any continuous hormonal medication or contraceptive, or Asherman's syndrome.
- The investigators will exclude participants with criteria that would affect our ability to obtaining meaningful MRI data such as
- presence of an intrauterine device (IUD). The use of an IUD potentially affects interpretability of MRI because it creates an imaging artifact in the endometrium extending to the myometrium.
- inability to read or comprehend the informed consent written in English,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naproxen SodiumSingle oral dose of 550 mg naproxen sodium (equivalent to 500 mg naproxen base), given as one tablet identical in size, shape, and appearance to the matching placebo. Administered once during a menstrual MRI visit (within 48 hours of menses onset), immediately after the pre-treatment scan and approximately 90 minutes before the post-treatment scan. Each participant receives naproxen at only one of the two MRI visits; the alternate visit (1-2 months later) uses placebo, per the randomized, quadruple-masked crossover. 550 mg naproxen sodium is the highest FDA-approved starting dose; the sodium salt formulation is used to speed absorption. | Drug | Naproxen First, Then Placebo, Placebo First, Then Naproxen |
| PlaceboSingle oral placebo pill containing no active drug, matched in size, shape, and appearance to the 550 mg naproxen sodium tablet and supplied in coded containers by the clinical research pharmacy. Administered once during a menstrual MRI visit on the same schedule as naproxen (immediately after the pre-treatment scan, approximately 90 minutes before the post-treatment scan). Each participant receives placebo at only one of the two MRI visits; the alternate visit uses naproxen, per the randomized, quadruple-masked crossover. | Drug | Naproxen First, Then Placebo, Placebo First, Then Naproxen |
Primary outcome
Number of Participants With Concordant Phenotype Assignment at Both MRI Visits
Time frame: Two menstrual MRI visits separated by 1 to 2 menstrual cycles (approximately 4 to 8 weeks).
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Each participant's two menstrual MRI scans were independently assigned to one of these phenotypes. A participant was counted as concordant if both scans were assigned to the same phenotype. Reported as the number and percentage of participants with concordant assignment.
Frequency of Uterine Contractions and BOLD Oxygenation-desaturation Events by Menstrual Pain Phenotype
Time frame: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). This measure reports the mean number of uterine contractions and BOLD oxygenation-desaturation events detected per 10-minute scan within each phenotype. R2* and arterial spin labeling sequences were not acquired in this round and were not included in phenotyping.
Mean Duration of Individual Uterine Contractions by Menstrual Pain Phenotype
Time frame: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). This measure reports the mean duration of an individual uterine contraction within each phenotype. Duration was quantified as the number of HASTE frames spanning each contraction, acquired at 2 frames per second, and is reported here in seconds. Longer values indicate contractions of greater individual duration.
Myometrial and Junctional Zone Thickness by Menstrual Pain Phenotype
Time frame: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). This measure reports mean myometrial and junctional zone thickness, measured in millimetres at the anterior and posterior uterine wall, within each phenotype.
BOLD Signal Intensity and Desaturation Dip Magnitude by Menstrual Pain Phenotype
Time frame: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Phenotypes were derived post hoc by principal component analysis and Ward hierarchical clustering of eleven HASTE and BOLD signal variables from the pre-dose menstrual MRI scan, at the scan level; each participant contributed up to two scans (84 participants, 119 scans). A desaturation event is a transient drop in BOLD signal. Baseline signal intensity is the mean BOLD signal preceding a desaturation event; minimum signal intensity is the mean signal at the nadir of the event; range of signal change is the difference between them. Higher baseline and minimum values indicate greater BOLD signal, and a larger range indicates a deeper desaturation, i.e. a greater transient drop in oxygenation. Scans with no desaturation event were assigned a nadir equal to baseline and a range of zero. Values are in arbitrary scanner signal intensity units and are not comparable across studies.
Percentage Change in BOLD Signal From Baseline by Menstrual Pain Phenotype
Time frame: Pre-dose menstrual MRI scan at each MRI visit; each scan approximately 1 hour.
Menstrual pain phenotypes were derived post hoc rather than assigned. Eleven quantitative signal variables extracted from HASTE and BOLD sequences of the pre-dose menstrual MRI scan were reduced by principal component analysis (6 components retained), and scans were grouped by Ward hierarchical clustering, which yielded three reproducible phenotypes. Clustering was performed at the scan level; each participant contributed up to two scans (84 participants, 119 scans). Percentage signal change expresses the magnitude of the BOLD desaturation as a proportion of baseline signal intensity, so larger values indicate a deeper transient drop in oxygenation. It is defined only where a desaturation event was detected; scans without a detected event were assigned a value of zero. Phenotype P2 was characterized by near-absent BOLD activity, so its distribution consists predominantly of these structural zeros.
Change in Junctional Zone Thickness From Pre-dose to Post-dose Scan, Naproxen Versus Placebo
Time frame: Pre-dose scan to post-dose scan at each of two menstrual MRI visits; the post-dose scan began approximately 90 minutes after dosing (each scan approximately 1 hour).
Within-subject change in junctional zone thickness, measured in millimetres, from the pre-dose to the post-dose scan, compared between the naproxen and placebo conditions in participants with primary dysmenorrhea. Change is calculated as post-dose minus pre-dose, so positive values indicate greater thickness after dosing. Each participant contributed a change score under both conditions. Row numbers analyzed differ because not every participant had both scans measurable at both wall locations. Post-dose BOLD sequences were successfully acquired at only 5 of 39 crossover visit pairs, and R2* and arterial spin labeling sequences were not acquired in this round, so no naproxen-versus-placebo comparison is reported for those signal families.
Change in Uterine Contraction Frequency From Pre-dose to Post-dose Scan, Naproxen Versus Placebo
Time frame: Pre-dose scan to post-dose scan at each of two menstrual MRI visits; the post-dose scan began approximately 90 minutes after dosing (each scan approximately 1 hour).
Within-subject change in the number of uterine contractions detected per 10-minute scan, from the pre-dose to the post-dose scan, compared between the naproxen and placebo conditions in participants with primary dysmenorrhea. Change is calculated as post-dose minus pre-dose, so positive values indicate more contractions after dosing. Each participant contributed a change score under both conditions. Post-dose BOLD sequences were successfully acquired at only 5 of 39 crossover visit pairs, and R2* and arterial spin labeling sequences were not acquired in this round, so no naproxen-versus-placebo comparison is reported for those signal families.
3 secondary outcomes
Agreement Between Primary and Sensitivity Phenotype Clustering Solutions (Adjusted Rand Index)
Time frame: Two menstrual MRI visits separated by 1 to 2 menstrual cycles (approximately 4 to 8 weeks). Pre-dose scan at each visit assessed.
Correlation of NSAID Resistance With Clinical/Psychosocial Covariates
Time frame: Peak pre-dose pain to 6 hours after naproxen dosing at the naproxen menstrual MRI visit.
Correlation of NSAID Resistance With Serum Naproxen (90 Min)
Time frame: Peak pre-dose pain to 6 hours after naproxen dosing at the naproxen menstrual MRI visit; serum was sampled 90 minutes after dosing.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin M Hellman, PhD principal investigator
Endeavor Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naproxen Sodium in people with Dysmenorrhea (Disorder) and Dysmenorrhea Primary, run by Endeavor Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Concordant Phenotype Assignment at Both MRI Visits (time frame: Two menstrual MRI visits separated by 1 to 2 menstrual cycles (approximately 4 to 8 weeks).). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.