Chronic Pain Risk Associated With Menstrual Period Pain

NCT ID: NCT02214550

Last Updated: 2023-06-18

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

353 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2021-01-31

Brief Summary

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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

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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.

Conditions

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Cystitis, Interstitial Dysmenorrhea Migraine Disorders Pelvic Pain Endometriosis Visceral Pain Chronic Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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D+COS-no OC

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

D+COS-cyclic microgestin 1/20

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.

Group Type ACTIVE_COMPARATOR

cyclic microgestin 1/20

Intervention Type DRUG

Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat

D+COS-continuous microgestin 1/20

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.

Group Type ACTIVE_COMPARATOR

continuous microgestin 1/20

Intervention Type DRUG

Continuous OC use - Pills containing hormones will be taken every day for 1 year

PBS-continuous microgestin 1/20

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.

Group Type ACTIVE_COMPARATOR

continuous microgestin 1/20

Intervention Type DRUG

Continuous OC use - Pills containing hormones will be taken every day for 1 year

No Intervention: Pain Discovery Aim

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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cyclic microgestin 1/20

Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat

Intervention Type DRUG

continuous microgestin 1/20

Continuous OC use - Pills containing hormones will be taken every day for 1 year

Intervention Type DRUG

Other Intervention Names

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loestrin 1/20 loestrin 1/20

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Endeavor Health

OTHER

Sponsor Role lead

Responsible Party

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Frank Tu

Division Director, Gynecological Pain and Minimally Invasive Surgery, Department of Obstetrics and Gynecology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Frank Tu, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Endeavor Health

Locations

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NorthShore University Health System

Evanston, Illinois, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 23370073 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18180636 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11349181 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23973396 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25010817 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37226937 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1R01DK100368-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

EH13-094

Identifier Type: -

Identifier Source: org_study_id

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