Clinical trial NCT02214550: Chronic Pain Risk Associated With Menstrual Period Pain
Official title: Deciphering the Hormonal and Nociceptive Mechanisms Underlying Bladder Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cystitis, Interstitial
Dysmenorrhea
Migraine Disorders
Pelvic Pain
Endometriosis
Visceral Pain
Chronic Pain
Keywords: Cystitis, Interstitial
Dysmenorrhea
Migraine Disorders
Cross Organ Sensitization
Pelvic Pain
Endometriosis
Contraceptives, Oral
Birth Control Pills
Painful Bladder Syndrome
Visceral Pain
Chronic Pain
Lead sponsor: Endeavor Health
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-08-12
Enrollment: 353
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if some women with dysmenorrhea (painful periods) are at higher future risk of developing chronic pelvic pain (CPP) and if oral contraceptives (OC) can be used to reverse this chronic pain risk.

Investigators will examine whether dysmenorrhea produces CPP via repetitive cross organ sensitization (COS) episodes. The use of cyclical OCs to eliminate dysmenorrhea is expected to reduce COS and decrease the risk of developing CPP.

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 develop chronic pelvic pain (CPP), yet women without dysmenorrhea rarely report CPP. CPP disorders such as irritable bowel syndrome (IBS) and painful bladder syndrome (PBS) can cause severe, unrelenting pain due to a lack of effective treatments.

This study consists of 2 aims.

Aim #1: To determine if dysmenorrhea with concomitant bladder pain sensitivity exhibits neurophysiological features consistent with established CPP. Women with chronic pain or dysmenorrhea without COS will be used as controls. Quantitative sensory testing (QST) and a noninvasive bladder pain test that investigators validated previously be used to determine whether impairments in descending inhibition and pelvic sensitivity are responsible for vulnerability to COS in women with dysmenorrhea. EEG will be recorded to look for differences in brain activity in response to sensory stimulation between participants cohorts.

Aim #2: To differentiate the individual contributions of circulating sex hormones and repeated sensitizing events (painful menses) on descending and peripheral mechanisms of bladder pain. The same QST/bladder pain measures studied in Aim #1 will be retested within the dysmenorrhea+COS group following a one-year randomized trial of cyclical OCs vs. continuous OCs vs. no treatment. An observational arm of PBS participants will receive continuous OCs and serve as controls.

Eligibility criteria: Inclusion Criteria:

All

* Reproductive age women (18-45)

For dysmenorrhea and D+COS group only:

* Participants must have had regular (22-45 day) menstrual cycles over at least a two month period preceding testing

Exclusion Criteria:

All

* presence of active pelvic or abdominal malignancies (primary or metastatic)
* active genitourinary infection in the last four weeks
* unable to read or comprehend the informed consent in English
* unwilling to undergo pelvic examination/testing
* presence of hypertension or risk for developing hypertension, and

For dysmenorrhea and D+COS group only:

* absence of regular menses (including current pregnancy, recent pregnancy, or active breast feeding) unwilling to take either cyclic or combined OCs
* unwilling to withdraw from OCs for two months prior to the sensory testing study visit.

Primary outcomes:
measure: Change in Participant Bladder Pain Sensitivity From Baseline.
timeFrame: 0 (baseline), 6 month, and 12 month visits
Secondary outcomes:
measure: Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline
timeFrame: 0 (baseline), 6 months and 12 months
measure: Differences in EEG Recorded Cortical Activity Among Participants
timeFrame: Baseline, 6 months and 12 months
Other outcomes:
Locations:
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
Study officials:
affiliation: Endeavor Health
name: Frank Tu, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tu FF, Epstein AE, Pozolo KE, Sexton DL, Melnyk AI, Hellman KM. A noninvasive bladder sensory test supports a role for dysmenorrhea increasing bladder noxious mechanosensitivity. Clin J Pain. 2013 Oct;29(10):883-90. doi: 10.1097/AJP.0b013e31827a71a3.
citation: Tu FF, Fitzgerald CM, Kuiken T, Farrell T, Norman Harden R. Vaginal pressure-pain thresholds: initial validation and reliability assessment in healthy women. Clin J Pain. 2008 Jan;24(1):45-50. doi: 10.1097/AJP.0b013e318156db13.
citation: Zondervan KT, Yudkin PL, Vessey MP, Jenkinson CP, Dawes MG, Barlow DH, Kennedy SH. Chronic pelvic pain in the community--symptoms, investigations, and diagnoses. Am J Obstet Gynecol. 2001 May;184(6):1149-55. doi: 10.1067/mob.2001.112904.
citation: Westling AM, Tu FF, Griffith JW, Hellman KM. The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors. Am J Obstet Gynecol. 2013 Nov;209(5):422.e1-422.e10. doi: 10.1016/j.ajog.2013.08.020. Epub 2013 Aug 22.
citation: Brotzner CP, Klimesch W, Doppelmayr M, Zauner A, Kerschbaum HH. Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives. Brain Res. 2014 Aug 19;1577(100):36-44. doi: 10.1016/j.brainres.2014.06.034. Epub 2014 Jul 7.