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Pelvic PainPhase 2GREATNCT06611501

Glycemic Regulation as Endometriosis Adjunct Treatment

A Phase 2 study testing Metformin Hydrochloride in people with Pelvic Pain and Endometriosis, run by Boston Children's Hospital at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 15 to 35 years, women only
Conditions the study is for
Pelvic Pain, Endometriosis
What is being tested?
Metformin Hydrochloride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
14 participants
Where
1 siteUnited States
Study dates
22 May 2025to Jan 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 35 years
  • Women only
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

United States1 site
  • Boston Children's Hospital

    Boston, Massachusetts, 02115

Other trials in United States

About this study

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?
Read more

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
Read the detailed 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.

Being tested
Metformin Hydrochloride, Placebo
Keywords
Pelvic pain, Pain, Metformin, Chronic pain, Physiological Effects of Drugs, Endometriosis, Female Urogenital Diseases, Genital Diseases, Female
Medical subject headings
Pelvic Pain, Endometriosis, Pain, Chronic Pain, Female Urogenital Diseases, Genital Diseases, Female

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metformin HydrochlorideDrug

    Metformin dosage titrated from 500 mg/daily for 2 weeks, then 1000 mg/daily for 2 weeks, 1500 mg/daily for 2 weeks, and then achieving 2000 mg/daily for a duration of 6 months of treatment.

  • PlaceboDrug

    Also called Placebo capsule

    1 tablet orally with evening meal for 2 weeks, then 1 tablet twice daily for 2 weeks, then 3 tablets split twice daily for 2 weeks, then 4 tablets split twice daily, for a total of 6 months of treatment.

Study groups in NCT06611501
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo tablets orally daily for a total of 6 months of treatment.
Receives: Drug: Placebo
MetforminExperimentalmetformin hydrochloride 500 mg capsules daily for a total of 6 months of treatment
Receives: Drug: Metformin Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in pain assessed by the Brief Pain Inventory Interference Scale (BPI) over 6 months

    The BPI Interference Scale is a 7-item composite pain measurement. This self-report measure assesses the extent to which pain interferes with various components of physical and emotional functioning and sleep. The items in this scale can be grouped into those that assess physical functioning (general activity; walking ability; normal work, including both work outside the home and housework), those that assess emotional functioning (mood; relations with people; enjoyment of life), and a single item that assess the extent to which pain interferes with sleep. The arithmetic mean of the seven interference items can be used as a measure of pain interference. The BPI is anchored between a scale of zero (no pain/interference) to ten (maximum pain/interference). The magnitude of treatment-associated change in BPI Interference Scale scores in open-label and randomized clinical trials ranges from 1 to 3 points, depending on the specific pain conditions and treatments studied.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

  2. Change in pain severity measured by Visual Analog Scale (VAS) over 6 months

    VAS: A measurement of pain intensity, assessed by a 0 to 10 numerical rating scale, to rate maximum and average pain intensity over the preceding 7 days. Higher scores indicate more severe pain intensity.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

  3. Change in emotional functioning assessed by Beck Depression Inventory-II (BDI) over 6 months

    The BDI is a 21-item self-report instrument that provides a rapid assessment of depressive symptoms. BDI has been used in many studies of chronic pain, including chronic pelvic pain and endometriosis. Total scores on the BDI range from 0 to 63. The BDI takes about 5-10 minutes to complete. Scores below 13 should be considered to reflect "minimal or no" depression, with score ranges of 14 to 19, 20 to 28, and 29 to 63 reflect "mild to moderate," "moderate to severe," and "severe" depression, respectively.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

  4. Change in ratings of overall improvement assessed by the Patient Global Impression of Change scale (PGIC)

    The PGIC is a seven-point single-item scale with options ranging from 'very much worse' to 'very much improved'. There has been widespread use of the PGIC in recent endometriosis clinical trials, as it readily interprets a person's evaluation of the importance of their improvement or worsening.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

Secondary outcomes (4)
  1. Change in quality of life, measured via Endometriosis Health Profile-30 (EHP-30)

    The EHP-30 is a reliable instrument and recommended by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. The questionnaire includes 30 questions in five subcategories, with each category addressing specific problem areas of pain, control and powerlessness, emotional wellbeing, social support, and self-image.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

  2. Changes in sexual satisfaction for participants who are sexually active measured by the New Sexual Satisfaction Scale

    The NSSS is a 20-item measure assessing sexual sensations, sexual presence/awareness, sexual exchange, emotional connection/closeness, and sexual activity. The full scale takes 5 minutes to complete.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

  3. Complete health and medication history assessed by the World Endometriosis Research Foundation (WERF) questionnaire

    Study participants will complete an expanded version of the WERF questionnaire for a complete health and medication history

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

  4. Changes in serum angiogenic/inflammatory markers

    Serum samples will also be obtained for measures of inflammation, to test the hypothesis that endometriosis-relevant inflammatory markers will decrease over time in patients treated with metformin compared to those receiving placebo. These markers will include IL-6, IL-8, and VEGF based on the results of prior studies in which metformin appeared to reduce these levels in humans with endometriosis and from endometriotic implants in rats. C-reactive protein (CRP) will also be assessed; CRP has been shown to be upregulated, especially when examined with a high sensitivity assay making it possible to detect subclinical inflammation in women with endometriosis.

    Measured: once at each of the three visits (at baseline, 3 months, 6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2024
  2. Study start22 May 2025
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
14 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06611501
Sponsor's protocol ID
IRB-P00049391
Acronym
GREAT
Status last verified
Jul 2026
First submitted
10 Sep 2024
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: IPD will not be shared so that patient privacy and confidentiality is maintained during this study.

Publications

  • Laufer MR, Goitein L, Bush M, Cramer DW, Emans SJ. Prevalence of endometriosis in adolescent girls with chronic pelvic pain not responding to conventional therapy. J Pediatr Adolesc Gynecol. 1997 Nov;10(4):199-202. doi: 10.1016/s1083-3188(97)70085-8.

    PubMed 9391902
  • Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT; World Endometriosis Research Foundation Global Study of Women's Health consortium. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011 Aug;96(2):366-373.e8. doi: 10.1016/j.fertnstert.2011.05.090. Epub 2011 Jun 30.

    PubMed 21718982
  • Brown J, Crawford TJ, Allen C, Hopewell S, Prentice A. Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev. 2017 Jan 23;1(1):CD004753. doi: 10.1002/14651858.CD004753.pub4.

    PubMed 28114727
  • Suda K, Nakaoka H, Yoshihara K, Ishiguro T, Tamura R, Mori Y, Yamawaki K, Adachi S, Takahashi T, Kase H, Tanaka K, Yamamoto T, Motoyama T, Inoue I, Enomoto T. Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium. Cell Rep. 2018 Aug 14;24(7):1777-1789. doi: 10.1016/j.celrep.2018.07.037.

    PubMed 30110635
  • Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, King K, Kvaskoff M, Nap A, Petersen K, Saridogan E, Tomassetti C, van Hanegem N, Vulliemoz N, Vermeulen N; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Feb 26;2022(2):hoac009. doi: 10.1093/hropen/hoac009. eCollection 2022.

    PubMed 35350465
  • Hossain MM, Nakayama K, Shanta K, Razia S, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Iida K, Kanno K, Ishikawa N, Kiyono T, Kyo S. Establishment of a Novel In Vitro Model of Endometriosis with Oncogenic KRAS and PIK3CA Mutations for Understanding the Underlying Biology and Molecular Pathogenesis. Cancers (Basel). 2021 Jun 25;13(13):3174. doi: 10.3390/cancers13133174.

    PubMed 34202354
  • Hopkins BD, Pauli C, Du X, Wang DG, Li X, Wu D, Amadiume SC, Goncalves MD, Hodakoski C, Lundquist MR, Bareja R, Ma Y, Harris EM, Sboner A, Beltran H, Rubin MA, Mukherjee S, Cantley LC. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018 Aug;560(7719):499-503. doi: 10.1038/s41586-018-0343-4. Epub 2018 Jul 4.

    PubMed 30051890
  • Qiang P, Shao Y, Sun YP, Zhang J, Chen LJ. Metformin inhibits proliferation and migration of endometrial cancer cells through regulating PI3K/AKT/MDM2 pathway. Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1778-1785. doi: 10.26355/eurrev_201902_17140.

    PubMed 30840303
  • Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, Ianculescu AG, Yue L, Lo JC, Burchard EG, Brett CM, Giacomini KM. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest. 2007 May;117(5):1422-31. doi: 10.1172/JCI30558.

    PubMed 17476361
  • Oner G, Ozcelik B, Ozgun MT, Serin IS, Ozturk F, Basbug M. The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model. Hum Reprod. 2010 Apr;25(4):932-7. doi: 10.1093/humrep/deq016. Epub 2010 Feb 3.

    PubMed 20133323
  • Yilmaz B, Sucak A, Kilic S, Aksakal O, Aksoy Y, Lortlar N, Sut N, Gungor T. Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9. Am J Obstet Gynecol. 2010 Apr;202(4):368.e1-8. doi: 10.1016/j.ajog.2009.10.873. Epub 2009 Dec 29.

    PubMed 20035912
  • Zhang H, Xue J, Li M, Zhao X, Wei D, Li C. Metformin regulates stromal-epithelial cells communication via Wnt2/beta-catenin signaling in endometriosis. Mol Cell Endocrinol. 2015 Sep 15;413:61-5. doi: 10.1016/j.mce.2015.06.011. Epub 2015 Jun 24.

    PubMed 26116230
  • Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-2701. doi: 10.2337/dci18-0033. Epub 2018 Oct 4.

    PubMed 30291106
  • Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193.

    PubMed 18463376
  • Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism. 1994 May;43(5):647-54. doi: 10.1016/0026-0495(94)90209-7.

    PubMed 8177055

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin Hydrochloride in people with Pelvic Pain and Endometriosis, run by Boston Children's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in pain assessed by the Brief Pain Inventory Interference Scale (BPI) over 6 months (time frame: once at each of the three visits (at baseline, 3 months, 6 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06611501, which also lists 86 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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