Clinical trial NCT06861920: NSAID Use for Treating Dysmenorrhea and Preventing Chronic Pelvic Pain
Official title: Targeting Interindividual Variability in NSAID Responses to Mitigate Chronic Pelvic Pain Risk in Dysmenorrhea
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Dysmenorrhea
Chronic Pelvic Pain
Pelvic Pain
Keywords: Painful Periods
NSAIDs
Chronic Pelvic Pain
Pelvic Pain
Periods
Lead sponsor: Endeavor Health
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of Chicago
name: University of Oklahoma
First posted: 2025-03-06
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if NSAIDs (i.e. naproxen sodium) can treat menstrual pain and prevent the development of chronic pelvic pain in menstruating adults with painful periods. The main questions it aims to answer are:

* Can non-menstrual pelvic pain reduction be predicted by menstrual pain response to NSAIDs?
* Will participants with the largest reductions in multi-site sensitivity following NSAID therapy have the largest reductions in non-menstrual pelvic pain?

Researchers will compare naproxen sodium to a placebo (a look-alike substance that contains no drug) to see if naproxen sodium works to treat painful periods.

Participants will:

* Take naproxen sodium or placebo during several days of their menstrual period every month for 1 year.
* Complete computer questionnaires and tests from home every 3 months.
* Complete at-home urine tests to measure hormones every few days for 1-year.
* Use a pin-prick to collect a small spot of blood, and use a pad or tampon to collect a sample of menstrual blood, and bring it to the research site twice over a 1-year period.
* Come to the research site twice over a 1-year period to complete sensory assessments and undergo a blood draw.

The major goal of the study is to develop a multivariable statistical model (see https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-24-021.html ) describing the factors that effectiveness of pain medication and risk for chronic pain


Eligibility criteria: Inclusion Criteria:

* aged 18-35
* individuals who menstruate, with painful periods
* regular menstrual cycles (every 22-35 days)

Exclusion Criteria:

* presence of active pelvic or abdominal malignancies (primary or metastatic)
* conditions associated with the absence of regular menses such as polycystic ovarian syndrome, pregnancy, or any current use of continuous hormonal medication or contraceptive
* unable to read or comprehend the informed consent in English
* presence of other diagnosed chronic back or pelvic pain conditions (including chronic back pain, fibromyalgia, bladder pain syndrome, irritable bowel syndrome, vulvar pain syndrome, and endometriosis-associated pelvic pain)
* having another diagnosed/symptomatic chronic pain condition besides migraines with an average pain score \>3/10 in the last month when not consuming pain relievers, or that requires daily treatment with opioids (ex. hydrocodone, oxycodone, codeine, morphine, hydromorphone, tapentadol, tramadol) or neuromodulators (also known sometimes as antidepressants \[ex. amitriptyline, nortriptyline, imipramine, duloxetine, milnacipran, venlafaxine\] or antiseizure medications \[ex. topiramate, gabapentin, pregabalin, carbamazepine, lamotrigine\])
* current or past history of stomach ulcers
* current or past history of gastrointestinal (GI) bleeding
* diagnosis of peptic ulcer disease
* current or past history of renal disorders
* current or past history of adrenal dysfunction
* diagnosis of liver disorders
* diagnosis of chronic acid reflex (i.e. GERD)
* Diagnosis of Crohn's disease or ulcerative colitis
* Coagulopathy
* Prolactinoma
* Von Willebrand disease
* Platelet disorders
* High blood pressure that is difficult to manage
* gastrointestinal conditions or surgeries that affect naproxen absorption
* bleeding disorders
* heart failure
* a history of stroke
* a history of heart attack
* active genitourinary or sexually transmitted infection
* allergy to non-steroidal anti-inflammatory drugs (NSAIDs) or their ingredients
* individuals who take the following medications: anticoagulants (i.e. warfarin), lithium, diuretics, antacids, angiotensin-converting enzyme (ACE) inhibitors, methotrexate, cholestyramine, or probenecids.
* Unmanaged diabetes (i.e. Fasting Blood Glucose: ≥ 126 mg/dL (≥ 7.0 mmol/L), Non-Fasting/Random Blood Glucose: ≥ 200 mg/dL (≥ 11.1 mmol/L), Hemoglobin A1c (HbA1c): ≥ 6.5%)
* Uncontrolled thyroid function (i.e. Hypothyroidism (Underactive Thyroid): Thyroid-Stimulating Hormone (TSH): \> 4.5 mIU/L (mild) or \> 10 mIU/L (severe) Free T4: Below the lower end of the reference range (usually \< 0.9 ng/dL)
* Hyperthyroidism (overactive thyroid) (i.e. TSH: \< 0.4 mIU/L (Suppressed or undetectable), Free T4: Above the upper end of the reference range (usually \> 2.0 ng/dL)
* Liver dysfunction (i.e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or bilirubin (unless known diagnosis of Gilbert's syndrome) ≥ 1.5 times the upper limit of the reference range)
* Kidney dysfunction (i.e. Serum creatinine \> 1.1 mg/dL.)

Primary outcomes:
measure: M1 = Non-Menstrual Pelvic Pain (NMPP) Mediation by Menstrual Pain
timeFrame: From enrollment to end of treatment at 1-year
measure: V1= Non-Menstrual Pelvic Pain (NMPP) mediation by Visceral-Visceral Convergence (VVC)
timeFrame: From enrollment to end of treatment at 1-year
measure: Change in Non-Menstrual Pelvic Pain (NMPP) adjusted for holistic factors
timeFrame: From enrollment to end of treatment at 1-year
Secondary outcomes:
Other outcomes:
measure: Trial effects of NSAIDs on Non-Menstrual Pelvic Pain (NMPP)
timeFrame: From enrollment to end of treatment at 1-year
measure: Trial effects of NSAIDs on chronic pelvic pain
timeFrame: From enrollment to end of treatment at 1-year
Locations:
city: Evanston
country: United States
facility: Endeavor Health
state: Illinois
Study officials:
References:
citation: Tu FF, Datta A, Atashroo D, Senapati S, Roth G, Clauw DJ, Hellman KM. Clinical profile of comorbid dysmenorrhea and bladder sensitivity: a cross-sectional analysis. Am J Obstet Gynecol. 2020 Jun;222(6):594.e1-594.e11. doi: 10.1016/j.ajog.2019.12.010. Epub 2019 Dec 20.
citation: Hellman KM, Roth GE, Dillane KE, Garrison EF, Oladosu FA, Clauw DJ, Tu FF. Dysmenorrhea subtypes exhibit differential quantitative sensory assessment profiles. Pain. 2020 Jun;161(6):1227-1236. doi: 10.1097/j.pain.0000000000001826.
citation: Kmiecik MJ, Tu FF, Silton RL, Dillane KE, Roth GE, Harte SE, Hellman KM. Cortical Mechanisms of Visual Hypersensitivity in Women at Risk for Chronic Pelvic Pain. medRxiv [Preprint]. 2021 Jan 18:2020.12.03.20242032. doi: 10.1101/2020.12.03.20242032.
citation: Shlobin AE, Tu FF, Sain CR, Kmiecik MJ, Kantarovich D, Singh L, Wang CE, Hellman KM. Bladder Pain Sensitivity Is a Potential Risk Factor for Irritable Bowel Syndrome. Dig Dis Sci. 2023 Jul;68(7):3092-3102. doi: 10.1007/s10620-023-07868-7. Epub 2023 Mar 7.
citation: Kmiecik MJ, Tu FF, Clauw DJ, Hellman KM. Multimodal hypersensitivity derived from quantitative sensory testing predicts pelvic pain outcome: an observational cohort study. Pain. 2023 Sep 1;164(9):2070-2083. doi: 10.1097/j.pain.0000000000002909. Epub 2023 Apr 27.