Mechanistic Characterization of Uterine Pain

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 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.

Conditions

• Dysmenorrhea (Disorder)
• Dysmenorrhea Primary
• Dysmenorrhea Secondary
• Endometrial Diseases
• Leiomyoma
• Fibroid Uterus

Interventions

DRUG

Naproxen Sodium

Participants will be randomized to take either a placebo pill or a single 550 mg naproxen sodium pill.

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Endeavor Health

  lead OTHER

Principal Investigators

• Kevin M Hellman, PhD · Endeavor Health

Study Design

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-10-25

Primary Completion

2025-07-23

Completion

2025-07-23

FDA Drug

Yes

Countries

• United States

Study Locations