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

NCT05900336 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2023P001489
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-steroidal Anti-inflammatory Drug; Dysmenorrhea; Menstrual Pain

Outcome Measures

Primary Outcomes (2)

• Overall Non-steroidal Anti-inflammatory Drug (NSAID) Response

  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.

  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

• Urinary Naproxen Concentration

  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).

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

Secondary Outcomes (4)

• Placebo Cycle Response

  4 hours after dose is taken.

• Non-steroidal Anti-inflammatory Drug (NSAID) Cycle Response

  4 hours after dose is taken.

• Urinary PGF2α Concentration

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

• Urinary PGE Concentration

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

Study Arms (2)

Sodium Naproxen first

EXPERIMENTAL

Participants take the dose of sodium naproxen during the first menstrual cycle and take the placebo during the second menstrual cycle.

Drug: Sodium Naproxen; Drug: Placebo

Placebo first

EXPERIMENTAL

Participants take the dose of placebo during the first menstrual cycle and take the sodium naproxen during the second menstrual cycle.

Drug: Sodium Naproxen; Drug: Placebo

Interventions

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).

Placebo first; Sodium Naproxen first

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 first; Sodium Naproxen first

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mclean Hospital: lead
• United States Department of Defense: collaborator
• Endeavor Health: collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Dysmenorrhea

Interventions

Naproxen

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pelvic Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Laura A. Payne
• Organization: McLean Hospital

LPayne@mclean.harvard.edu

(617) 855-3478

Study Officials

• Laura Payne, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 12, 2023
• Study Start: March 25, 2024
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: September 22, 2026
• Results First Posted: September 22, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)