Estradiol-mediated Inflammation and Central Sensitization in the Pathophysiology of Endometriosis-associated Pelvic Pain

NCT07100782 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: HUM00229564R01HD108253
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better understand how hormone suppression with Relugolix Combination-Therapy (CT) affects pelvic pain, inflammation, and pain sensitivity in women with moderate-to-severe endometriosis associated pelvic pain.

Conditions

Endometriosis; Pelvic Pain

Keywords

Relugolix Combination Therapy; Endo-EPIC (Alternative study acronym/title)

Outcome Measures

Primary Outcomes (2)

• Change score in lipopolysaccharide (LPS)-stimulated Macrophage inflammatory protein-1 alpha (MIP1-α) levels

  LPS-stimulated MIP1-α levels measured from whole blood

  baseline and week 12 visit

• Change score for functional magnetic resonance imaging (fMRI) connectivity of the somatosensory cortices to the default-mode network

  Assessed using a functional connectivity MRI (fcMRI) at rest and applied pain

  baseline and week 12 visit

Secondary Outcomes (2)

• Change scores for pelvic pain interference

  baseline and week 12 visit

• Change score for temporal summation at the forearm

  baseline and week 12 visit

Study Arms (1)

Relugolix CT

EXPERIMENTAL

All participants will have the same intervention, but approximately half of those enrolled will have widespread pain and half will not. Approximately 65 participants with widespread pain will receive relugolix CT (relugolix 40mg, estradiol 1 mg, norethindrone acetate 0.5 mg once daily) daily for 24 weeks, and 65 participants without widespread pain will receive relugolix CT for 24 weeks.

Drug: Relugolix CT

Interventions

Relugolix CT DRUG

Study medication will be provided by Sumitomo in pill bottles containing an 84-day supply of relugolix 40mg, estradiol 1mg, norethindrone acetate 0.5mg (Relugolix Combination therapy).

Also known as: Myfembree

Relugolix CT

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal woman between age 18 and 49 years (inclusive) at the time of consent. Menopause is defined as amenorrhea \>1 year unrelated to hormonal suppression.
• History of endometriosis diagnosed by surgery (visual or biopsy confirmed), ultrasound, or MRI within 10 years of study entry
• History of self-reported moderate to severe pelvic pain for ≥ 6 months' duration at time of screening visit.
• Willingness to participate in a relugolix CT drug intervention trial
• Has not used an injectable hormone therapy in the past 6 months (e.g. DepoProvera®, DepoLupron®).
• Willingness to 30-60 day washout interval of oral, vaginal, transdermal, intrauterine hormonal therapies prior to study initiation if applicable
• Willingness to use 2 forms of non-hormonal contraception during the entire duration of the study period or has had a history of a bilateral tubal occlusion procedure at least 3 months prior to screening (tubal ligation or hysteroscopic occlusion method)
• Willing to undergo quantitative sensory testing (QST), fMRI and other study procedures
• Ability to read and speak English to allow for written informed consent, phenotyping, and patient-reported outcomes measures
• Meet criteria to participate in QST and fMRI. These include:
• Normal visual acuity or correctable (with corrective lenses- glasses or contacts) to at least 20/40 for reading instructions in the MRI and visual sensitivity testing
• No contraindications to MRI (e.g., metal implants, claustrophobia)
• Willingness to refrain from pain medications such as NSAIDs, acetaminophen, and opioids for 12 hours prior to neuroimaging and QST
• Willingness to refrain from alcohol and nicotine on day of QST and neuroimaging (alcohol and nicotine consumption is allowed after testing is completed)
• Willingness to refrain from physical activity or exercise that would cause muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable)

You may not qualify if:

• Contraindication to the use of relugolix CT (high risk of arterial or venous thrombotic, or thromboembolic disorder, known osteoporosis, current or history of breast cancer or other hormone sensitive malignancy, known hepatic impairment or disease, undiagnosed abnormal uterine bleeding, known hypersensitivity to components of relugolix CT).
• Concurrent participation in other therapeutic trials
• Pregnant, lactating, less than 6 months postpartum, or planning a pregnancy within next 12 months
• Planning pelvic or abdominal surgery during study period
• Prior major surgery in the past 4 months that involves incisions on the abdomen, chest, head, other than a skin biopsy (hysteroscopy, endometrial biopsy is ok to include).
• Planning to initiate a new adjunctive pain treatment during study treatment (e.g. cognitive behavioral therapy, physical therapy, acupuncture). Participants may be enrolled if these treatments are completed prior to trial or using stable therapies.
• History of hysterectomy and/or bilateral oophorectomy
• Clinically significant gynecologic condition such as significant endometrial pathology (e.g. endometrial hyperplasia), persistent ovarian cyst larger than 5 cm, largest uterine dimension \>15 centimeters and not planning an additional intervention or treatment for endometriosis, or another uterine or ovarian condition during the study period. Patients may be enrolled in this study if they were previously successfully treated for these conditions. Patients must have undergone pelvic ultrasound or MRI in the past 6 months, and provide results (or release of records to obtain results)
• History or current evidence of psychosis, current suicide risk or attempt within 2 years of study (note: participants with mood disorders such as depression or anxiety will not be excluded)
• Chronic opioid, alcohol, and/or illicit drug use
• History of substance abuse within past one year
• Unable or unwilling to discontinue opioids analgesics within 48 hours of the dense phenotyping study visits
• Medical conditions that may significantly interfere with relugolix CT efficacy, ability to fully comply or would make it unsafe for participants to take part in the study, including but not limited to: morbid obesity with Body Mass Index \> 45, uncontrolled autoimmune/inflammatory diseases, significant cardiopulmonary disease (e.g., angina, congestive heart failure, uncontrolled hypertension, severe cardiac valvular disease, Chronic Obstructive Pulmonary Disease (COPD), chronic asthma), renal or liver disease (e.g. cirrhosis, hepatitis), uncontrolled endocrine or allergic disorders (e.g., hypothyroidism, diabetes, allergic rhinitis), neurologic conditions (e.g., multiple sclerosis, prior stroke, neurological tumor), severe physical impairment (e.g., blindness, deafness, paraplegia); and active malignancy (any malignancy except for localized dermatologic cancer).
• Any impairment, activity or situation that in the judgment of the Study Coordinator or Principal Investigator would prevent safe or satisfactory completion of the study protocol.
• Individuals receiving or applying for compensation or disability and other aspects associated with potential secondary gain per self-report;

Sponsors & Collaborators

• University of Michigan: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Endometriosis; Pelvic Pain

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sawsan As-Sanie, MD, MPH

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Andrew Schrepf, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathy Scott

CONTACT

734-998-7022; jrsj@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: blind to pain
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obstetrics and Gynecology

Model Details: All investigators will be blinded to wide-spread pain (WSP) status until final analysis.

Study Record Dates

• First Submitted: July 27, 2025
• First Posted: August 3, 2025
• Study Start: December 8, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: De-identified datasets will be made available after publication of the primary study results and/or at the conclusion of the NICHD-funded grant study period, barring any no-cost extension. Data will remain available for at least 3 years beyond the end date of the study.
• Access Criteria: Data will be made publicly available through the NIH data repositories, per NIH policies including data use agreements and protection of identifying information.

Locations

US (1)