Chronic Pain Risk Associated With Menstrual Period Pain (CRAMPP)

May 17, 2023 updated by: Frank Tu, NorthShore University HealthSystem

Deciphering the Hormonal and Nociceptive Mechanisms Underlying Bladder Pain

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

353

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: 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.
Active Comparator: 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.
Drug: 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
Other Names:
  • loestrin 1/20
Active Comparator: 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.
Drug: continuous microgestin 1/20
Continuous OC use - Pills containing hormones will be taken every day for 1 year
Other Names:
  • loestrin 1/20
Active Comparator: 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.
Drug: continuous microgestin 1/20
Continuous OC use - Pills containing hormones will be taken every day for 1 year
Other Names:
  • loestrin 1/20
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Participant Bladder Pain Sensitivity From Baseline.
Time Frame: 0 (baseline), 6 month, and 12 month visits
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 initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in pain. Bladder pain ratings at first urge will be used at the outcome measure.
0 (baseline), 6 month, and 12 month visits

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline
Time Frame: 0 (baseline), 6 months and 12 months
Results from the QST testing performed at initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in sensitivity from baseline. Specifically, measure reported is the pressure pain threshold in newtons observed at the transition from pressure to pain transvaginally at the 12 o'clock position (anteriorly against the bladder). Lower values (pressure) indicate greater sensitivity.
0 (baseline), 6 months and 12 months
Differences in EEG Recorded Cortical Activity Among Participants
Time Frame: Baseline, 6 months and 12 months
We obtained the peak alpha frequency at the right and left parietal occipital electrodes and averages of the two sides were assessed at Baseline, 6 month, and 12 Month to determine whether differences in resting state brain activity at parieto-occipital electrode sites are affected by oral contraceptives
Baseline, 6 months and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NorthShore University HealthSystem

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Frank Tu, MD, MPH, Northshore University Healthsystem

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2014

Primary Completion (Actual)

November 1, 2020

Study Completion (Actual)

January 1, 2021

Study Registration Dates

First Submitted

August 8, 2014

First Submitted That Met QC Criteria

August 8, 2014

First Posted (Estimated)

August 12, 2014

Study Record Updates

Last Update Posted (Estimated)

June 19, 2023

Last Update Submitted That Met QC Criteria

May 17, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EH13-094
  • 1R01DK100368-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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