Skip to main content
OpenTrials
Completed

NCT Number: NCT05900336

Non-Steroidal Anti-Inflammatory Drug (NSAID) Response and Central Sensitization of Pain in Women With Dysmenorrhea

Menstrual pain is the most common gynecological complaint and the leading cause of school and work absences in reproductive-age girls and women. One of the primary treatments for menstrual pain is use of nonsteroidal anti-inflammatory drugs (NSAIDs; over-the-counter medications such as naproxen, ibuprofen, or aspirin), although up to 18% of women do not get pain relief from these medications. One reason for this may be due to central sensitization of pain, which is when alterations in the central nervous system change how pain is processed in the brain and experienced. Determining the role of central sensitization in menstrual pain is important because central sensitization is associated with the development of chronic pain. Understanding the relationship between NSAID response and central sensitization is important because it could indicate women who may go on to develop chronic pain later in life. This study would directly address this question. Identifying women at risk for chronic pain would help target new treatments to this vulnerable group to ideally prevent pain from becoming chronic. This is particularly important for women in the military because the severity of menstrual pain is associated with missed work, such that in active-duty military women, less than 4.4% with mild menstrual pain missed work, whereas 20.7% of women with moderate to severe menstrual pain missed work. Addressing the significant impact of menstrual pain for military women will help reducing suffering and potentially decrease the risk of developing future chronic pain problems in this population.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Dysmenorrhea Menstrual Pain Menstruation Disturbances Neurologic Manifestations Non-steroidal Anti-inflammatory Drug Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Pelvic Pain Signs and Symptoms

Age range

18 year–50 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

McLean Hospital

Belmont, Massachusetts, 02478, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female aged 18-50 years
  • Menstrual pain rated at least 6/10 on a 0 (no pain) to 10 (worst pain possible) NRS for all menstrual cycles in the previous 6 months
  • Regular menstrual cycles over the past year (at least 9 in the previous 12 months)
  • Self-reported menstrual cycle averaging 22-35 days
  • Access to a smartphone and email, and willing/able to receive text messages
  • Able to read and understand English
  • Ability and willingness to provide written informed consent.

Exclusion criteria

  • Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation
  • Variable levels of menstrual pain in the previous 6 months
  • Self-reported symptoms consistent with a chronic pain condition (e.g., pain in any body area lasting longer than 3 months) or previous diagnosis of a chronic pain condition
  • Currently pregnant or breastfeeding
  • History of pelvic inflammatory disease or sexually transmitted disease
  • Acute illness or injury that would potentially impact pain task performance (e.g., fever, flu symptoms) or that affect sensitivity of the extremities (e.g., Reynaud's disease)
  • Allergy to naproxen or having a health condition that contradicts use of naproxen or affects naproxen metabolism (e.g., kidney disease)
  • History of high blood pressure or anemia (due to possible complications from NSAID use).

Treatment and study plan

Sodium Naproxen

Drug

One dose of 550mg sodium naproxen taken at the onset of at least moderate pain after menstrual bleeding has started (i.e., at least 6/10 on the 0-10 numeric rating scale).

Placebo

Drug

One dose of placebo capsule taken at the onset of at least moderate pain after menstrual bleeding has started (i.e., at least 6/10 on the 0-10 numeric rating scale).

Primary outcomes

  1. Overall Non-steroidal Anti-inflammatory Drug (NSAID) Response

    Time frame: 4 hrs after taking dose during the 2nd medicated menstrual period (i.e., 4 hrs after the first occurrence of pain >= 6 on the 0-10 scale after menstrual bleeding has started during the 2nd medicated menstrual period); # of days varies by participant

    NSAID response will be calculated by comparing change in menstrual pain ratings following NSAID to change in menstrual pain ratings following placebo. Calculated by subtracting the placebo cycle response measure from the NSAID cycle response measure. This will result in a single measure indicative of the degree of NSAID response, while controlling for placebo effects. Possible range: -20 (min) to 20 (max). The value of each intervention separately can be associated with a better or worse outcome, as indicated below. The value of this measure is not independently clinically meaningful (i.e., not related to better or worse outcomes) as it is the result of comparing an individual to themself. Negative values indicate that the participant demonstrated more response to naproxen than they did to placebo; positive values indicate that the participant demonstrated more response to placebo than they did to naproxen.

  2. Urinary Naproxen Concentration

    Time frame: Four hours after taking the dose (either Naproxen or placebo).

    Concentration of naproxen measured in the urine sample. Measured in nanograms of Naproxen Glucuronide per mg creatinine. Value is not independently clinically meaningful (i.e., not related to better or worse outcomes).

Secondary outcomes

  1. Placebo Cycle Response

    Time frame: 4 hours after dose is taken.

    Change in menstrual pain rating on a 0 (no pain) to 10 (worst pain possible) numeric rating scale before and after the dose is taken. Calculated by subtracting the pre-dose rating from the post-dose rating. Possible range: -10 (min) to 10 (max). Lower scores indicate better outcome.

  2. Non-steroidal Anti-inflammatory Drug (NSAID) Cycle Response

    Time frame: 4 hours after dose is taken.

    Change in menstrual pain rating on a 0 (no pain) to 10 (worst pain possible) numeric rating scale before and after the dose is taken. Calculated by subtracting the pre-dose rating from the post-dose rating. Possible range: -10 (min) to 10 (max). Lower scores indicate better outcome.

  3. Urinary PGF2α Concentration

    Time frame: Four hours after taking the dose (either Naproxen or placebo).

    Concentration of prostaglandin F2α (PGF2α) measured in the urine sample. Value is not independently clinically meaningful (i.e., not related to better or worse outcomes).

  4. Urinary PGE Concentration

    Time frame: Four hours after taking the dose (either Naproxen or placebo).

    New information since initial submission indicated that this outcome measure (Prostaglandin E; PGE) would not be detectable in urine. No PGE analyses were conducted.

Interested in participating?

Completed

Looking for future studies?

Notify Me

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Collaborators

  • Endeavor Health
  • United States Department of Defense

Registry information

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jun 12, 2023
Registry last updated
Sep 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.