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

Dysmenorrhea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05900336
• Other study ID #: 2023P001489
• Status: Recruiting
• Phase: Phase 4
• Start date: March 25, 2024
• Est. completion date: May 31, 2025

Study information

• Verified date: March 2024
• Source: Mclean Hospital
• Contact: Laura Seidman
• Phone: (339) 368-4364
• Email: LCSeidman[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Female aged 18-50 years

2. 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

3. Regular menstrual cycles over the past year (at least 9 in the previous 12 months)

4. Self-reported menstrual cycle averaging 22-35 days

5. Access to a smartphone and email, and willing/able to receive text messages

6. Able to read and understand English

7. Ability and willingness to provide written informed consent.

Exclusion Criteria:

1. Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation

2. Variable levels of menstrual pain in the previous 6 months

3. 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

4. Currently pregnant or breastfeeding

5. History of pelvic inflammatory disease or sexually transmitted disease

6. 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)

7. Allergy to naproxen or having a health condition that contradicts use of naproxen or affects naproxen metabolism (e.g., kidney disease)

8. History of high blood pressure or anemia (due to possible complications from NSAID use).

Related Conditions & MeSH terms

• Dysmenorrhea
• Menstrual Pain

Intervention

Drug:
• Sodium Naproxen
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
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).

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Mclean Hospital	NorthShore University HealthSystem, United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall 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	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
Primary	Urinary naproxen concentration	Concentration of naproxen measured in the urine sample.	Four hours after taking the dose (either Naproxen or placebo).
Primary	Conditioned pain modulation (CPM)	Conditioned pain modulation (CPM) assesses pain inhibition. CPM is calculated as the change in pain50 between when the pressure is applied by itself (test stimulus) and when it is applied while the participant's hand is submerged in cold water (conditioning stimulus).	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Placebo cycle response	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.	4 hours after dose is taken.
Secondary	NSAID cycle response	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.	4 hours after dose is taken.
Secondary	Urinary PGF2a concentration	Concentration of prostaglandin F2a (PGF2a) measured in the urine sample.	Four hours after taking the dose (either Naproxen or placebo).
Secondary	Urinary PGE concentration	Concentration of prostaglandin E (PGE) measured in the urine sample.	Four hours after taking the dose (either Naproxen or placebo).
Secondary	pain50	The amount of pressure in kg/cm2 at the first instance of a pain rating of at least 50/100 during an ascending series of 5-second pressures applied to the dominant thumbnail. [Pressures begin at 0.5 kg/cm2 and increase by steps of 0.5 kg/cm2. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=70 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.]	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	pain70	The amount of pressure in kg/cm2 at the first instance of a pain rating of at least 70/100 during an ascending series of 5-second pressures applied to the dominant thumbnail. [Pressures begin at 0.5 kg/cm2 and increase by steps of 0.5 kg/cm2. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=70 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.]	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Pressure pain sensitivity (PPS)	The pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 2.0 kg/cm2 application of pressure to the dominant thumbnail bed.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Pressure pain tolerance (PPT)	The last rated pressure delivered in a series of increasing pressure applications to the right thumbnail bed. Each application of pressure lasts for 5 seconds. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=70 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Trapezius pressure pain sensitivity (TPPS)	The pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 4.0 kg/cm2 application of pressure to the dominant trapezius muscle.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Time to bladder first sensation	The amount of time in minutes from when the participant began drinking water during the bladder pain task to when she first feels able to urinate.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Pain at bladder first sensation	The amount of bladder pain rated on a 0 (no pain) to 100 (worst pain possible) during the bladder pain task when the participant first feels able to urinate.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Time to bladder first urge	The amount of time in minutes from when the participant began drinking water during the bladder pain task to when she reaches a point at which she would request to use the restroom if participating in an activity.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Pain at bladder first urge	The amount of bladder pain rated on a 0 (no pain) to 100 (worst pain possible) during the bladder pain task when the participant reaches a point at which she would request to use the restroom if participating in an activity.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Time to bladder maximum tolerance	The amount of time in minutes from when the participant began drinking water during the bladder pain task to when she is no longer able to hold more urine.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Secondary	Pain at bladder maximum tolerance	The amount of bladder pain rated on a 0 (no pain) to 100 (worst pain possible) during the bladder pain task when the participant is no longer able to hold more urine.	At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)