CRAMPP: Chronic Pain Risk Associated With Menstrual Period Pain
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Endometrial shedding during the menstrual cycle elicits profound changes in neuronal activity and cytokines 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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Pain Discovery Aim This arm will receive no treatments and will be used as reference to compare to the other groups. 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. |
|
| No Intervention: D+COS-no OC For Aim #2, ten participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. Aim #1 testing 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 For Aim #2, 26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. Aim #1 testing will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years. |
Drug: 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
Continuous OC use - Pills containing hormones will be taken every day for 1 year
Other Names:
|
| Active Comparator: D+COS-continuous microgestin 1/20 For Aim #2, 26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. Aim #1 testing will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years. |
Drug: 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
Continuous OC use - Pills containing hormones will be taken every day for 1 year
Other Names:
|
| Active Comparator: PBS-continuous microgestin 1/20 For Aim #2, 26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. Aim #1 testing will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years. |
Drug: 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
Continuous OC use - Pills containing hormones will be taken every day for 1 year
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in participant bladder pain sensitivity from baseline. [6 month and 12 month visits]
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.
Secondary Outcome Measures
- Change in Quantitative Sensory Testing (QST) parameters regarding pelvic hyperalgesia from 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
- Differences in EEG recorded cortical activity among participants [Time Frame: Baseline, 6 months and 12 months]
Results from EEG site specific ERPs and brainwave related variables performed at Baseline, 6 month, and 12 Month to determine whether differences in brain activity are responsible for sensitivity.
Eligibility Criteria
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:
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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 Aim #1 study visit.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | NorthShore University Health System | Evanston | Illinois | United States | 60201 |
Sponsors and Collaborators
- NorthShore University HealthSystem
- National Institutes of Health (NIH)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Frank Tu, MD, MPH, NorthShore University HealthSystem
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- 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.
- 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.
- 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.
- EH13-094
- 1R01DK100368-01