NCT04145518: MCUP

Mechanistic Characterization of Uterine Pain

Completed Phase 4 Last updated 12 December 2025

What this trial tests

Phase 4 trial testing Naproxen Sodium in Dysmenorrhea (Disorder) in 183 participants. Completed in 23 July 2025.

Timeline

25 October 2019

Primary endpoint
23 July 2025

23 July 2025

Quick facts

Lead sponsor	Endeavor Health
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	health services research
Enrollment	183
Start date	25 October 2019
Primary completion	23 July 2025
Estimated completion	23 July 2025
Sites	1 location across United States

Drugs / interventions tested

• Naproxen Sodium — full drug profile →

Conditions studied

• Dysmenorrhea (Disorder) — all drugs for Dysmenorrhea (Disorder) →
• Dysmenorrhea Primary — all drugs for Dysmenorrhea Primary →
• Dysmenorrhea Secondary — all drugs for Dysmenorrhea Secondary →
• Endometrial Diseases — all drugs for Endometrial Diseases →

Sponsor

Endeavor Health — full company profile →

Who can join

Adults 18 to 45, female only, with Dysmenorrhea (Disorder) or Dysmenorrhea Primary. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Development and validation of a real-time method characterizing spontaneous pain in women with dysmenorrhea.
   Kantarovich D, Dillane KE, Garrison EF, Oladosu FA, et al · · 2021 · cited 3× · PMID 33590541 · DOI 10.1111/jog.14663
2. Menstrual Cycle Variation in MRI-Based Quantification of Intraluminal Gas in Women With and Without Dysmenorrhea.
   Oh H, Ehrenpreis ED, Tu FF, Dillane KE, et al · · 2022 · cited 2× · PMID 35634451 · DOI 10.3389/fpain.2022.720141