Glycemic Regulation as Endometriosis Adjunct Treatment (GREAT)

Boston Children's Hospital

Status and phase: Enrolling; Phase 2

Conditions: Pelvic Pain; Endometriosis

Treatments: Drug: Placebo; Drug: Metformin Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT06611501

IRB-P00049391

Details and patient eligibility

About

The goal of this pilot trial is to learn if a novel non-hormonal treatment, metformin hydrochloride, works to treat pelvic pain in young women with endometriosis. The main questions it aims to answer are:

• Is metformin superior to placebo in alleviating pain symptoms in young women with endometriosis?
• Does metformin alter systemic inflammatory markers over 6 months in young women with endometriosis?

Researchers will compare metformin to a placebo (a look-alike substance that contains no drug) to see if metformin works to treat pelvic pain.

Participants will:

• Take drug metformin or a placebo every day for 6 months
• Visit the clinic three times: once at baseline (pre-treatment), once at 3 months, and once at 6 months
• Keep a daily symptom diary to track pain, bleeding, and usage of any pain medications

Full description

Endometriosis is a chronic illness defined by the presence of endometrial glands and stroma outside the uterine lining. While prevalence estimates vary depending on the population studied, endometriosis is thought to affect approximately one in ten reproductive aged women, up to 50% of women with infertility, and up to 70% of adolescents with chronic pelvic pain. Over 10 million women in the United States have endometriosis and incur significantly higher direct and indirect healthcare costs than those without. Annual health care costs are estimated at $100 billion in the United States alone. While the majority of patients report the onset of endometriosis symptoms during adolescence, delays in diagnosis are common and range from 7 to 12 years. During these delays, women may suffer from debilitating symptoms interfering with school and social activities, and commonly experience reduced health-related quality of life and work productivity. When left untreated, endometriosis can progress significantly in over 50% of patients and result in a higher stage of disease. Therefore, timely intervention and maintenance of therapy is critical for preventing the progression of disease and patient burden.

Therapeutic options for endometriosis include surgical and medical management. Because surgery is not curative, long-term medical therapy is often advised to prevent recurrence of symptoms and retard the progression of disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for endometriosis-related pain but do not remove or decrease deposits of ectopic endometrium. Hormonal therapies are the mainstay of medical therapy as they can inhibit prostaglandin production that contributes to pain, and cause decidualization and atrophy of ectopic endometrial tissue. Unfortunately, hormonal treatments have varied degrees of success and no data support one treatment over another. Additionally, the treatment choice may be limited to medication side effects, availability, costs, and contraceptive needs. Hormonal treatments do not cure endometriosis; 11-19% of women may not experience any relief with medical therapy, and up to a third of women experience recurrence of pain symptoms after treatment cessation. Additionally, as endometriosis is predominantly a disease of young reproductive-aged women, patients may desire a treatment with a different mechanism of action that does not impact ovarian function and fertility. There remains an unmet clinical need among women with endometriosis for effective and well-tolerated medical therapies.

Metformin, an insulin-sensitizing oral biguanide, is approved for the treatment of type 2 diabetes. Several published studies using in vitro and animal models have implicated metformin with a regression of endometriotic implants and reduction of inflammatory activity. Yet, the mechanisms of action of metformin remain to be further elucidated. Only one prospective study to date has investigated the use of metformin in humans as monotherapy for endometriosis; this study had substantial limitations. Further investigation will be improved with participant and provider blinding, use of validated pain measures, and inclusion of a broader population of patients affected by endometriosis. A randomized clinical trial is necessary to investigate the mechanisms and efficacy of metformin as an anti-endometriotic drug.

Enrollment: 14 estimated patients

Sex: Female

Ages: 15 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female with surgically confirmed endometriosis, determined at laparoscopy
• Current use for at least 2 months duration of a consistent hormonal therapy for endometriosis (either combination hormonal contraceptives or progestin-only therapy)
• Current pelvic pain (score ≥ 3 on Visual Analog Scale) that has been present for at least 2 months prior to enrollment
• Age 15 years to 35 years and premenopausal
• Willingness to comply with visit schedule and protocol

Exclusion criteria

• Pre-menarche or post-menopause
• Diagnosis of Type 1 or Type 2 Diabetes Mellitus
• Severe renal dysfunction (creatinine >1.4 mg/dL or eGFR below 45 mL/minute/1.73 m2
• History of lactic acidosis or diabetic ketoacidosis
• ALT or AST > 2.5 times the upper limit of normal
• Significant mental or chronic systemic illness that might confound pain assessment or the inability to complete the study
• Current/planning pregnancy or breastfeeding
• Inability to read English

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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14 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo tablets orally daily for a total of 6 months of treatment.

Treatment:

Drug: Placebo

Metformin

Experimental group

Description:

metformin hydrochloride 500 mg capsules daily for a total of 6 months of treatment

Treatment:

Drug: Metformin Hydrochloride