Chronic Pain Risk Associated With Menstrual Period Pain

NCT02214550 | Completed Phase 4 Results DMC

• 2 other identifiers: EH13-0941R01DK100368-01
• Study Type: interventional
• Target: 353
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Cystitis, Interstitial; Dysmenorrhea; Migraine Disorders; Cross Organ Sensitization; Pelvic Pain; Endometriosis; Contraceptives, Oral; Birth Control Pills; Painful Bladder Syndrome; Visceral Pain; Chronic Pain

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline

  0 (baseline), 6 months and 12 months

• Differences in EEG Recorded Cortical Activity Among Participants

  Baseline, 6 months and 12 months

Study Arms (5)

D+COS-no OC

NO INTERVENTION

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

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

D+COS-continuous microgestin 1/20

ACTIVE COMPARATOR

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

PBS-continuous microgestin 1/20

ACTIVE COMPARATOR

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

No Intervention: Pain Discovery Aim

NO INTERVENTION

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.

Interventions

cyclic microgestin 1/20 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

Also known as: loestrin 1/20

D+COS-cyclic microgestin 1/20

continuous microgestin 1/20 DRUG

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

Also known as: loestrin 1/20

D+COS-continuous microgestin 1/20; PBS-continuous microgestin 1/20

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Endeavor Health: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Related Publications (6)

• 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.

  PMID: 23370073 BACKGROUND

• 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.

  PMID: 18180636 BACKGROUND

• 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.

  PMID: 11349181 BACKGROUND

• 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.

  PMID: 23973396 BACKGROUND

• 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.

  PMID: 25010817 BACKGROUND

• 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.

  PMID: 37226937 DERIVED

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Diseases, Female; Genital Diseases; Nociceptive Pain

Limitations and Caveats

Small sample size due to higher than expected refusal of participants with DYSB to randomize to an OCP limits generalizability. As noted above, nonserious adverse events are reported as the frequency of ever reporting an event on a form, of any intensity.

Results Point of Contact

• Title: Dr. Frank Tu
• Organization: NorthShore University HealthSystem

ftu@northshore.org

8475702520

Study Officials

• Frank Tu, MD, MPH

  Endeavor Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Director, Gynecological Pain and Minimally Invasive Surgery, Department of Obstetrics and Gynecology

Study Record Dates

• First Submitted: August 8, 2014
• First Posted: August 12, 2014
• Study Start: July 1, 2014
• Primary Completion: November 1, 2020
• Study Completion: January 1, 2021
• Last Updated: June 18, 2023
• Results First Posted: June 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)