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

Primary Purpose

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

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Sodium Naproxen
Placebo
Sponsored by
Mclean Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Dysmenorrhea

Eligibility Criteria

50 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

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).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Sodium Naproxen first

    Placebo first

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

    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
    Urinary naproxen concentration
    Concentration of naproxen measured in the urine sample.
    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).

    Secondary Outcome Measures

    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.
    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.
    Urinary PGF2α concentration
    Concentration of prostaglandin F2α (PGF2α) measured in the urine sample.
    Urinary PGE concentration
    Concentration of prostaglandin E (PGE) measured in the urine sample.
    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.]
    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.]
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    May 31, 2023
    Last Updated
    October 17, 2023
    Sponsor
    Mclean Hospital
    Collaborators
    United States Department of Defense, NorthShore University HealthSystem
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05900336
    Brief Title
    Non-Steroidal Anti-Inflammatory Drug (NSAID) Response and Central Sensitization of Pain in Women With Dysmenorrhea
    Official Title
    Non-Steroidal Anti-Inflammatory Drug (NSAID) Response and Central Sensitization of Pain in Women With Dysmenorrhea
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2024 (Anticipated)
    Primary Completion Date
    May 31, 2025 (Anticipated)
    Study Completion Date
    May 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Mclean Hospital
    Collaborators
    United States Department of Defense, NorthShore University HealthSystem

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dysmenorrhea, Menstrual Pain, Non-steroidal Anti-inflammatory Drug

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 4
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    70 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Sodium Naproxen first
    Arm Type
    Experimental
    Arm Description
    Participants take the dose of sodium naproxen during the first menstrual cycle and take the placebo during the second menstrual cycle.
    Arm Title
    Placebo first
    Arm Type
    Experimental
    Arm Description
    Participants take the dose of placebo during the first menstrual cycle and take the sodium naproxen during the second menstrual cycle.
    Intervention Type
    Drug
    Intervention Name(s)
    Sodium Naproxen
    Intervention Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    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 Outcome Measure Information:
    Title
    Overall NSAID response
    Description
    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
    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
    Title
    Urinary naproxen concentration
    Description
    Concentration of naproxen measured in the urine sample.
    Time Frame
    Four hours after taking the dose (either Naproxen or placebo).
    Title
    Conditioned pain modulation (CPM)
    Description
    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).
    Time Frame
    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 Outcome Measure Information:
    Title
    Placebo cycle response
    Description
    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.
    Time Frame
    4 hours after dose is taken.
    Title
    NSAID cycle response
    Description
    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.
    Time Frame
    4 hours after dose is taken.
    Title
    Urinary PGF2α concentration
    Description
    Concentration of prostaglandin F2α (PGF2α) measured in the urine sample.
    Time Frame
    Four hours after taking the dose (either Naproxen or placebo).
    Title
    Urinary PGE concentration
    Description
    Concentration of prostaglandin E (PGE) measured in the urine sample.
    Time Frame
    Four hours after taking the dose (either Naproxen or placebo).
    Title
    pain50
    Description
    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.]
    Time Frame
    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)
    Title
    pain70
    Description
    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.]
    Time Frame
    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)
    Title
    Pressure pain sensitivity (PPS)
    Description
    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.
    Time Frame
    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)
    Title
    Pressure pain tolerance (PPT)
    Description
    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.
    Time Frame
    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)
    Title
    Trapezius pressure pain sensitivity (TPPS)
    Description
    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.
    Time Frame
    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)
    Title
    Time to bladder first sensation
    Description
    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.
    Time Frame
    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)
    Title
    Pain at bladder first sensation
    Description
    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.
    Time Frame
    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)
    Title
    Time to bladder first urge
    Description
    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.
    Time Frame
    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)
    Title
    Pain at bladder first urge
    Description
    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.
    Time Frame
    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)
    Title
    Time to bladder maximum tolerance
    Description
    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.
    Time Frame
    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)
    Title
    Pain at bladder maximum tolerance
    Description
    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.
    Time Frame
    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)

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    50 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Laura Seidman
    Phone
    (339) 368-4364
    Email
    LCSeidman@mclean.harvard.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Laura Payne, PhD
    Phone
    (617) 855-3478
    Email
    LPayne@mclean.harvard.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Laura Payne, PhD
    Organizational Affiliation
    Mclean Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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