Chronic Pain Risk Associated With Menstrual Period Pain

Chronic Pain Clinical Trial

— CRAMPP  

Official title:

Deciphering the Hormonal and Nociceptive Mechanisms Underlying Bladder Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02214550
• Other study ID #: EH13-094
• Secondary ID: 1R01DK100368-01
• Status: Completed
• Phase: Phase 4
• Start date: July 2014
• Est. completion date: January 2021

Study information

• Verified date: May 2023
• Source: NorthShore University HealthSystem
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: January 2021
• Est. primary completion date: November 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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
• continuous microgestin 1/20
Continuous OC use - Pills containing hormones will be taken every day for 1 year

Locations

Country	Name	City	State
United States	NorthShore University Health System	Evanston	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
NorthShore University HealthSystem	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Participant Bladder Pain Sensitivity From Baseline.	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	Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline	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
Secondary	Differences in EEG Recorded Cortical Activity Among Participants	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

External Links

•   Click here for more information about this study: CRAMPP