Examining the Role of Improved NSAID Management in Treating Dysmenorrhea and Bladder Pain

The goal of this study is to see if optimized use of naproxen for treatment of dysmenorrhea will improve pain report from baseline. In addition, we will determine whether cross-organ influences from the uterus on bladder pain sensitivity change from baseline after reduced menstrual pain experience over six months. Finally, a battery of quantitative sensory tests and EEG measures of sensory sensitivity will be used to evaluate mechanisms associated with improvements in menstrual and bladder pain.

Study Overview

• Status: Completed
• Conditions: Pain; Dysmenorrhea
• Intervention / Treatment: Drug: Naproxen

Detailed Description

Endometrial shedding during the menstrual cycle elicits profound changes in neuronal activity and cytokine concentrations producing moderate to severe pelvic pain in more than 20% of reproductive-age women. One out of every five of those women in turn will experience chronic pelvic pain (CPP) which may be in part due to cross-organ neural sensitization.

In this study we will establish whether prophylactic and adequate dosages of naproxen are capable of reducing menstrual pain more than *** use.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Reproductive-age women (age 18-45) with dysmenorrhea
• Average menstrual pain ≥ 5/10 (0=no pain and 10=the worst imaginable pain) on at least one day during menses or during withdrawal uterine bleeding from cyclic OCs without painkillers
• Menstrual pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament
• Indication the participant has attempted to resolve pain by medical means (including NSAIDs and/or OCPs)

Exclusion Criteria:

• Presence of active pelvic or abdominal malignancies (primary or metastatic)
• Absence of regular menses (including current pregnancy, recent pregnancy, or active breast feeding)
• Active genitourinary infection in the last four weeks
• Unable to read or comprehend the informed consent in English
• Unwilling to complete study procedures
• Presence of hypertension or risk for developing hypertension
• Unwillingness to take naproxen and/or placebo
• Contradictions to taking naproxen (allergies, kidney disease, anemia, alcoholism, cardiovascular disease, stomach or intestinal ulcer or abnormal liver function)
• Formal urological diagnosis such as overactive bladder or bladder pain syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Dysmenorrhea; We will look at the effects of naproxen 500mg use on pain starting just before and during menses.	Drug: Naproxen; Participants will take naproxen 500mg BID before and for the first 3 days of their period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Menstrual Pain	Score on a scale. Specifically, we used a Numeric Rating Scale (NRS)- 0 through 10 scale with 0 being no pain and 10 worst pain imaginable. Results for the worst menstrual pain score on an NRS from the 6-8 mth menstrual pain diary will be compared to baseline pretreatment diary worst pain score.	6-8 months
Change in Participant Bladder Pain Sensitivity From Baseline	Score on a scale. Specifically, we used a Visual Analog Scale- 0 through 100 scale with 0 being no pain and 100 worst pain imaginable. Results from the visual analog scale (VAS) of the bladder filling test at the baseline and 6-8 mph followup visit will be compared to determine if naproxen treatment of menstrual pain affected bladder pain. Bladder pain ratings at first urge will be used at the outcome measure.	6-8 months

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem
• Investigators: Principal Investigator: Frank Tu, MD, MPH, NorthShore University HealthSystem

Publications and helpful links

General Publications

• Chan WY, Dawood MY, Fuchs F. Prostaglandins in primary dysmenorrhea. Comparison of prophylactic and nonprophylactic treatment with ibuprofen and use of oral contraceptives. Am J Med. 1981 Mar;70(3):535-41. doi: 10.1016/0002-9343(81)90576-3.
• Oladosu FA, Tu FF, Hellman KM. Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment. Am J Obstet Gynecol. 2018 Apr;218(4):390-400. doi: 10.1016/j.ajog.2017.08.108. Epub 2017 Sep 6.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2018
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: NSAID; visceral pain; cross-organ sensitivity; bladder pain
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Menstruation Disturbances; Pelvic Pain; Dysmenorrhea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: EH18-128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: Yes