Chronic Pain Risk Associated With Menstrual Period Pain (CRAMPP)

NorthShore University HealthSystem

Status and phase: Completed; Phase 4

Conditions: Cystitis, Interstitial; Migraine Disorders; Pelvic Pain; Dysmenorrhea; Chronic Pain; Visceral Pain; Endometriosis

Treatments: Drug: cyclic microgestin 1/20; Drug: continuous microgestin 1/20

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02214550

1R01DK100368-01 (U.S. NIH Grant/Contract)

EH13-094

Details and patient eligibility

About

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.

Full 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.

Enrollment: 353 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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353 participants in 5 patient groups

D+COS-no OC

No Intervention group

Description:

Ten participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.

D+COS-cyclic microgestin 1/20

Active Comparator group

Description:

26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.

Treatment:

Drug: cyclic microgestin 1/20

D+COS-continuous microgestin 1/20

Active Comparator group

Description:

26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.

Treatment:

Drug: continuous microgestin 1/20

PBS-continuous microgestin 1/20

Active Comparator group

Description:

26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.

Treatment:

Drug: continuous microgestin 1/20

No Intervention: Pain Discovery Aim

No Intervention group

Description:

255 Reproductive-age women (18-45) will be identified and divided into 5 groups Healthy Controls Chronic Pain (Positive Controls) Dysmenorrhea (D) Dysmenorrhea with Cross Organ Sensitization (D+COS) Painful bladder syndrome (PBS)/interstitial cystitis (IC) After a screening, dysmenorrhea with COS and PBS participants will be compared with controls. Daily Diaries will be completed for 1-3 months. During the luteal phase of the participants' menstrual cycle or a predetermined time, participants will complete aim #1 testing consisting of a battery of questionnaires, bladder sensitivity testing, quantitative sensory testing (QST), a blood draw and EEG testing. All participants will also complete a yearly follow-up questionnaire for 5 years.