Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Clinical Phase
PHASE2
Total Enrollment
14 participants
Study Classification
INTERVENTIONAL
Study Start Date
2025-05-22
Study Completion Date
2027-01-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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
* 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
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Randomized, Placebo-controlled, Double-blind Study of KLH-2109 in Patients With Endometriosis (2)
NCT01533532
Endometriosis
COMPLETED
PHASE2
Dopamine Receptor Agonist Therapy for Pain Relief in Women Suffering From Endometriosis: A Pilot Study
NCT02542410
Endometriosis
COMPLETED
PHASE2
Subdermal Implant-bioabsorbable Gestrinone Pellet for Endometriosis Pelvic Pain Treatment
NCT05570786
Deep Endometriosis
Pelvic Pain
COMPLETED
PHASE2
Identification of Endometriosis and Migraine Criteria in Women With the Comorbidity of Both Conditions in Comparison With Women Who Only Suffer From Endometriosis - A Pilot Study
NCT04816357
Endometriosis
Migraine
COMPLETED
Megestrol Acetate Plus LNG-IUS in Young Women With Early Endometrial Cancer
NCT03241914
Endometrial Neoplasm Malignant Stage I
COMPLETED
PHASE2/PHASE3
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Pelvic Pain
Endometriosis
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
TRIPLE
Participants
Caregivers
Investigators
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Placebo
Placebo tablets orally daily for a total of 6 months of treatment.
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
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.
Metformin
metformin hydrochloride 500 mg capsules daily for a total of 6 months of treatment
Group Type
EXPERIMENTAL
Metformin Hydrochloride
Intervention Type
DRUG
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Metformin Hydrochloride
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.
Intervention Type
DRUG
Placebo
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.
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Placebo capsule
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
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
* 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
* 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
Minimum Eligible Age
15 Years
Maximum Eligible Age
35 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Boston Children's Hospital
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Jessica Shim
Assistant Professor, Division of Gynecology
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Jessica Shim, MD
Role: PRINCIPAL_INVESTIGATOR
Boston Children's Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Boston Children's Hospital
Boston, Massachusetts, United States
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
United States
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006 Jun;21(6):1416-25. doi: 10.1093/humrep/del025. Epub 2006 Feb 24.
Reference Type
BACKGROUND
Khattab S, Fotouh IA, Mohesn IA, Metwally M, Moaz M. Use of metformin for prevention of ovarian hyperstimulation syndrome: a novel approach. Reprod Biomed Online. 2006 Aug;13(2):194-7. doi: 10.1016/s1472-6483(10)60614-1.
Reference Type
BACKGROUND
Hostalek U, Campbell I. Metformin for diabetes prevention: update of the evidence base. Curr Med Res Opin. 2021 Oct;37(10):1705-1717. doi: 10.1080/03007995.2021.1955667. Epub 2021 Jul 28.
Reference Type
BACKGROUND
Praharaj SK, Jana AK, Goyal N, Sinha VK. Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis. Br J Clin Pharmacol. 2011 Mar;71(3):377-82. doi: 10.1111/j.1365-2125.2010.03783.x.
Reference Type
BACKGROUND
LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev. 2021 Jan 28;42(1):77-96. doi: 10.1210/endrev/bnaa023.
Reference Type
BACKGROUND
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-1585. doi: 10.1007/s00125-017-4342-z. Epub 2017 Aug 3.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
Jackson RA, Hawa MI, Jaspan JB, Sim BM, Disilvio L, Featherbe D, Kurtz AB. Mechanism of metformin action in non-insulin-dependent diabetes. Diabetes. 1987 May;36(5):632-40. doi: 10.2337/diab.36.5.632.
Reference Type
BACKGROUND
Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Manneras-Holm L, Stahlman M, Olsson LM, Serino M, Planas-Felix M, Xifra G, Mercader JM, Torrents D, Burcelin R, Ricart W, Perkins R, Fernandez-Real JM, Backhed F. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017 Jul;23(7):850-858. doi: 10.1038/nm.4345. Epub 2017 May 22.
Reference Type
BACKGROUND
Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. JAMA. 2016 Jul 19;316(3):313-24. doi: 10.1001/jama.2016.9400.
Reference Type
BACKGROUND
Takemura Y, Osuga Y, Yoshino O, Hasegawa A, Hirata T, Hirota Y, Nose E, Morimoto C, Harada M, Koga K, Tajima T, Yano T, Taketani Y. Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab. 2007 Aug;92(8):3213-8. doi: 10.1210/jc.2006-2486. Epub 2007 May 15.
Reference Type
BACKGROUND
Nodler JL, DiVasta AD, Vitonis AF, Karevicius S, Malsch M, Sarda V, Fadayomi A, Harris HR, Missmer SA. Supplementation with vitamin D or omega-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2020 Jul 1;112(1):229-236. doi: 10.1093/ajcn/nqaa096.
Reference Type
BACKGROUND
DiVasta AD, Stamoulis C, Gallagher JS, Laufer MR, Anchan R, Hornstein MD. Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. F S Rep. 2021 Jul 24;2(4):454-461. doi: 10.1016/j.xfre.2021.07.003. eCollection 2021 Dec.
Reference Type
BACKGROUND
Yanovski JA, Krakoff J, Salaita CG, McDuffie JR, Kozlosky M, Sebring NG, Reynolds JC, Brady SM, Calis KA. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes. 2011 Feb;60(2):477-85. doi: 10.2337/db10-1185. Epub 2011 Jan 12.
Reference Type
BACKGROUND
Adeyemo MA, McDuffie JR, Kozlosky M, Krakoff J, Calis KA, Brady SM, Yanovski JA. Effects of metformin on energy intake and satiety in obese children. Diabetes Obes Metab. 2015 Apr;17(4):363-70. doi: 10.1111/dom.12426. Epub 2015 Jan 11.
Reference Type
BACKGROUND
Srinivasan S, Ambler GR, Baur LA, Garnett SP, Tepsa M, Yap F, Ward GM, Cowell CT. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. J Clin Endocrinol Metab. 2006 Jun;91(6):2074-80. doi: 10.1210/jc.2006-0241. Epub 2006 Apr 4.
Reference Type
BACKGROUND
Mauras N, DelGiorno C, Hossain J, Bird K, Killen K, Merinbaum D, Weltman A, Damaso L, Balagopal P. Metformin use in children with obesity and normal glucose tolerance--effects on cardiovascular markers and intrahepatic fat. J Pediatr Endocrinol Metab. 2012;25(1-2):33-40. doi: 10.1515/jpem-2011-0450.
Reference Type
BACKGROUND
Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008 Feb;9(2):105-21. doi: 10.1016/j.jpain.2007.09.005. Epub 2007 Dec 11.
Reference Type
BACKGROUND
Keller S, Bann CM, Dodd SL, Schein J, Mendoza TR, Cleeland CS. Validity of the brief pain inventory for use in documenting the outcomes of patients with noncancer pain. Clin J Pain. 2004 Sep-Oct;20(5):309-18. doi: 10.1097/00002508-200409000-00005.
Reference Type
BACKGROUND
Smarr KL, Keefer AL. Measures of depression and depressive symptoms: Beck Depression Inventory-II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S454-66. doi: 10.1002/acr.20556. No abstract available.
Reference Type
BACKGROUND
Pokrzywinski R, Soliman AM, Surrey E, Snabes MC, Coyne KS. Psychometric assessment of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain. J Patient Rep Outcomes. 2020 Oct 27;4(1):86. doi: 10.1186/s41687-020-00257-y.
Reference Type
BACKGROUND
Bourdel N, Chauvet P, Billone V, Douridas G, Fauconnier A, Gerbaud L, Canis M. Systematic review of quality of life measures in patients with endometriosis. PLoS One. 2019 Jan 10;14(1):e0208464. doi: 10.1371/journal.pone.0208464. eCollection 2019.
Reference Type
BACKGROUND
Vitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck Louis GM, Hummelshoj L, Giudice LC, Stratton P, Adamson GD, Becker CM, Zondervan KT, Missmer SA; WERF EPHect Working Group. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: II. Clinical and covariate phenotype data collection in endometriosis research. Fertil Steril. 2014 Nov;102(5):1223-32. doi: 10.1016/j.fertnstert.2014.07.1244. Epub 2014 Sep 22.
Reference Type
BACKGROUND
Othman Eel-D, Hornung D, Salem HT, Khalifa EA, El-Metwally TH, Al-Hendy A. Serum cytokines as biomarkers for nonsurgical prediction of endometriosis. Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):240-6. doi: 10.1016/j.ejogrb.2007.05.001. Epub 2007 Jun 19.
Reference Type
BACKGROUND
Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002 Feb;17(2):426-31. doi: 10.1093/humrep/17.2.426.
Reference Type
BACKGROUND
Xavier P, Belo L, Beires J, Rebelo I, Martinez-de-Oliveira J, Lunet N, Barros H. Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet. 2006 Jan;273(4):227-31. doi: 10.1007/s00404-005-0080-4. Epub 2005 Oct 6.
Reference Type
BACKGROUND
Karbalaee-Hasani A, Khadive T, Eskandari M, Shahidi S, Mosavi M, Nejadebrahimi Z, Khalkhali L, Sangdari A, Mohammadi D, Soltani A, Khodabandehloo H, Hosseini H, Koushki M. Effect of Metformin on Circulating Levels of Inflammatory Markers in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Ann Pharmacother. 2021 Sep;55(9):1096-1109. doi: 10.1177/1060028020985303. Epub 2021 Jan 7.
Reference Type
BACKGROUND
Seifarth C, Schehler B, Schneider HJ. Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):27-31. doi: 10.1055/s-0032-1327734. Epub 2012 Nov 12.
Reference Type
BACKGROUND
Kujawska-Luczak M, Musialik K, Szulinska M, Swora-Cwynar E, Kargulewicz A, Grzymislawska M, Pupek-Musialik D, Bogdanski P. The effect of orlistat versus metformin on body composition and insulin resistance in obese premenopausal women: 3-month randomized prospective open-label study. Arch Med Sci. 2017 Jun;13(4):725-731. doi: 10.5114/aoms.2016.62014. Epub 2016 Aug 29.
Reference Type
BACKGROUND
DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995 Aug 31;333(9):541-9. doi: 10.1056/NEJM199508313330902.
Reference Type
BACKGROUND
Reese KA, Reddy S, Rock JA. Endometriosis in an adolescent population: the Emory experience. J Pediatr Adolesc Gynecol. 1996 Aug;9(3):125-8. doi: 10.1016/s1083-3188(96)70021-9.
Reference Type
BACKGROUND
Fujita Y, Inagaki N. Metformin: New Preparations and Nonglycemic Benefits. Curr Diab Rep. 2017 Jan;17(1):5. doi: 10.1007/s11892-017-0829-8.
Reference Type
BACKGROUND
Kashi Z, Mahrooz A, Kianmehr A, Alizadeh A. The Role of Metformin Response in Lipid Metabolism in Patients with Recent-Onset Type 2 Diabetes: HbA1c Level as a Criterion for Designating Patients as Responders or Nonresponders to Metformin. PLoS One. 2016 Mar 15;11(3):e0151543. doi: 10.1371/journal.pone.0151543. eCollection 2016.
Reference Type
BACKGROUND
Abrao MS, Podgaec S, Filho BM, Ramos LO, Pinotti JA, de Oliveira RM. The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod. 1997 Nov;12(11):2523-7. doi: 10.1093/humrep/12.11.2523.
Reference Type
BACKGROUND
May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010 Nov-Dec;16(6):651-74. doi: 10.1093/humupd/dmq009. Epub 2010 May 12.
Reference Type
BACKGROUND
Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002;54(2):82-7. doi: 10.1159/000067717.
Reference Type
BACKGROUND
Ohata Y, Harada T, Miyakoda H, Taniguchi F, Iwabe T, Terakawa N. Serum interleukin-8 levels are elevated in patients with ovarian endometrioma. Fertil Steril. 2008 Oct;90(4):994-9. doi: 10.1016/j.fertnstert.2007.07.1355. Epub 2008 Jul 16.
Reference Type
BACKGROUND
Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril. 1998 Sep;70(3):425-31. doi: 10.1016/s0015-0282(98)00204-0.
Reference Type
BACKGROUND
Stulhofer A, Busko V, Brouillard P. Development and bicultural validation of the new sexual satisfaction scale. J Sex Res. 2010 Jul;47(4):257-68. doi: 10.1080/00224490903100561.
Reference Type
BACKGROUND
van de Burgt TJ, Hendriks JC, Kluivers KB. Quality of life in endometriosis: evaluation of the Dutch-version Endometriosis Health Profile-30 (EHP-30). Fertil Steril. 2011 Apr;95(5):1863-5. doi: 10.1016/j.fertnstert.2010.11.009. Epub 2010 Dec 3.
Reference Type
BACKGROUND
Jones G, Kennedy S, Barnard A, Wong J, Jenkinson C. Development of an endometriosis quality-of-life instrument: The Endometriosis Health Profile-30. Obstet Gynecol. 2001 Aug;98(2):258-64. doi: 10.1016/s0029-7844(01)01433-8.
Reference Type
BACKGROUND
Waller KG, Shaw RW. Endometriosis, pelvic pain, and psychological functioning. Fertil Steril. 1995 Apr;63(4):796-800. doi: 10.1016/s0015-0282(16)57484-6.
Reference Type
BACKGROUND
Kames LD, Rapkin AJ, Naliboff BD, Afifi S, Ferrer-Brechner T. Effectiveness of an interdisciplinary pain management program for the treatment of chronic pelvic pain. Pain. 1990 Apr;41(1):41-46. doi: 10.1016/0304-3959(90)91107-T.
Reference Type
BACKGROUND
Vincent K, Kennedy S, Stratton P. Pain scoring in endometriosis: entry criteria and outcome measures for clinical trials. Report from the Art and Science of Endometriosis meeting. Fertil Steril. 2010 Jan;93(1):62-7. doi: 10.1016/j.fertnstert.2008.09.056. Epub 2008 Nov 5.
Reference Type
BACKGROUND
Raichle KA, Osborne TL, Jensen MP, Cardenas D. The reliability and validity of pain interference measures in persons with spinal cord injury. J Pain. 2006 Mar;7(3):179-86. doi: 10.1016/j.jpain.2005.10.007.
Reference Type
BACKGROUND
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.
Reference Type
BACKGROUND
Bourdel N, Alves J, Pickering G, Ramilo I, Roman H, Canis M. Systematic review of endometriosis pain assessment: how to choose a scale? Hum Reprod Update. 2015 Jan-Feb;21(1):136-52. doi: 10.1093/humupd/dmu046. Epub 2014 Sep 1.
Reference Type
BACKGROUND
Siavash M, Tabbakhian M, Sabzghabaee AM, Razavi N. Severity of Gastrointestinal Side Effects of Metformin Tablet Compared to Metformin Capsule in Type 2 Diabetes Mellitus Patients. J Res Pharm Pract. 2017 Apr-Jun;6(2):73-76. doi: 10.4103/jrpp.JRPP_17_2.
Reference Type
BACKGROUND
Rojas LB, Gomes MB. Metformin: an old but still the best treatment for type 2 diabetes. Diabetol Metab Syndr. 2013 Feb 15;5(1):6. doi: 10.1186/1758-5996-5-6.
Reference Type
BACKGROUND
Reiser E, Lanbach J, Bottcher B, Toth B. Non-Hormonal Treatment Options for Regulation of Menstrual Cycle in Adolescents with PCOS. J Clin Med. 2022 Dec 21;12(1):67. doi: 10.3390/jcm12010067.
Reference Type
BACKGROUND
Flyckt R, Kim S, Falcone T. Surgical Management of Endometriosis in Patients with Chronic Pelvic Pain. Semin Reprod Med. 2017 Jan;35(1):54-64. doi: 10.1055/s-0036-1597306. Epub 2017 Jan 3.
Reference Type
BACKGROUND
Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Jun 7;164(11):740-51. doi: 10.7326/M15-2650. Epub 2016 Apr 19.
Reference Type
BACKGROUND
Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med. 1995 Aug 31;333(9):550-4. doi: 10.1056/NEJM199508313330903.
Reference Type
BACKGROUND
Sivalingam VN, Myers J, Nicholas S, Balen AH, Crosbie EJ. Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications. Hum Reprod Update. 2014 Nov-Dec;20(6):853-68. doi: 10.1093/humupd/dmu037. Epub 2014 Jul 10.
Reference Type
BACKGROUND
Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by the American Diabetes Association. Diabetes Care. 2018 Dec;41(12):2648-2668. doi: 10.2337/dci18-0052. No abstract available.
Reference Type
BACKGROUND
Yari S, Khoei HH, Saber M, Esfandiari F, Moini A, Shahhoseini M. Metformin attenuates expression of angiogenic and inflammatory genes in human endometriotic stromal cells. Exp Cell Res. 2021 Jul 15;404(2):112659. doi: 10.1016/j.yexcr.2021.112659. Epub 2021 May 19.
Reference Type
BACKGROUND
Stochino-Loi E, Major AL, Gillon TER, Ayoubi JM, Feki A, Bouquet de Joliniere J. Metformin, the Rise of a New Medical Therapy for Endometriosis? A Systematic Review of the Literature. Front Med (Lausanne). 2021 May 11;8:581311. doi: 10.3389/fmed.2021.581311. eCollection 2021.
Reference Type
BACKGROUND
Kimber-Trojnar Z, Dluski DF, Wierzchowska-Opoka M, Ruszala M, Leszczynska-Gorzelak B. Metformin as a Potential Treatment Option for Endometriosis. Cancers (Basel). 2022 Jan 24;14(3):577. doi: 10.3390/cancers14030577.
Reference Type
BACKGROUND
Hopkins BD, Goncalves MD, Cantley LC. Insulin-PI3K signalling: an evolutionarily insulated metabolic driver of cancer. Nat Rev Endocrinol. 2020 May;16(5):276-283. doi: 10.1038/s41574-020-0329-9. Epub 2020 Mar 3.
Reference Type
BACKGROUND
Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005 Jan;11(1):63-70. doi: 10.1038/nm1173. Epub 2004 Dec 26.
Reference Type
BACKGROUND
Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noe M, Horlings HM, Lum A, Jones S, Senz J, Seckin T, Ho J, Wu RC, Lac V, Ogawa H, Tessier-Cloutier B, Alhassan R, Wang A, Wang Y, Cohen JD, Wong F, Hasanovic A, Orr N, Zhang M, Popoli M, McMahon W, Wood LD, Mattox A, Allaire C, Segars J, Williams C, Tomasetti C, Boyd N, Kinzler KW, Gilks CB, Diaz L, Wang TL, Vogelstein B, Yong PJ, Huntsman DG, Shih IM. Cancer-Associated Mutations in Endometriosis without Cancer. N Engl J Med. 2017 May 11;376(19):1835-1848. doi: 10.1056/NEJMoa1614814.
Reference Type
BACKGROUND
Becker CM, Gattrell WT, Gude K, Singh SS. Reevaluating response and failure of medical treatment of endometriosis: a systematic review. Fertil Steril. 2017 Jul;108(1):125-136. doi: 10.1016/j.fertnstert.2017.05.004.
Reference Type
BACKGROUND
Olive DL. Medical therapy of endometriosis. Semin Reprod Med. 2003 May;21(2):209-22. doi: 10.1055/s-2003-41327.
Reference Type
BACKGROUND
Shim JY, Laufer MR. Adolescent Endometriosis: An Update. J Pediatr Adolesc Gynecol. 2020 Apr;33(2):112-119. doi: 10.1016/j.jpag.2019.11.011. Epub 2019 Dec 5.
Reference Type
BACKGROUND
Hoshiai H, Ishikawa M, Sawatari Y, Noda K, Fukaya T. Laparoscopic evaluation of the onset and progression of endometriosis. Am J Obstet Gynecol. 1993 Sep;169(3):714-9. doi: 10.1016/0002-9378(93)90649-4.
Reference Type
BACKGROUND
DiVasta AD, Vitonis AF, Laufer MR, Missmer SA. Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood. Am J Obstet Gynecol. 2018 Mar;218(3):324.e1-324.e11. doi: 10.1016/j.ajog.2017.12.007. Epub 2017 Dec 13.
Reference Type
BACKGROUND
Pugsley Z, Ballard K. Management of endometriosis in general practice: the pathway to diagnosis. Br J Gen Pract. 2007 Jun;57(539):470-6.
Reference Type
BACKGROUND
Ballweg ML. Big picture of endometriosis helps provide guidance on approach to teens: comparative historical data show endo starting younger, is more severe. J Pediatr Adolesc Gynecol. 2003 Jun;16(3 Suppl):S21-6. doi: 10.1016/s1083-3188(03)00063-9. No abstract available.
Reference Type
BACKGROUND
Simoens S, Hummelshoj L, D'Hooghe T. Endometriosis: cost estimates and methodological perspective. Hum Reprod Update. 2007 Jul-Aug;13(4):395-404. doi: 10.1093/humupd/dmm010.
Reference Type
BACKGROUND
Soliman AM, Surrey E, Bonafede M, Nelson JK, Castelli-Haley J. Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States. Adv Ther. 2018 Mar;35(3):408-423. doi: 10.1007/s12325-018-0667-3. Epub 2018 Feb 15.
Reference Type
BACKGROUND
Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010 Aug;27(8):441-7. doi: 10.1007/s10815-010-9436-1. Epub 2010 Jun 25.
Reference Type
BACKGROUND
Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K, Missmer SA. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018 Aug;51:1-15. doi: 10.1016/j.bpobgyn.2018.06.001. Epub 2018 Jul 3.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IRB-P00049391
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Levonorgestrel-releasing Intrauterine System in Patients With Endometriosis
NCT02158845
COMPLETED
PHASE4
Safety and Efficacy Study of MT-2990 in Women With Endometriosis
NCT03840993
COMPLETED
PHASE2
Mifepristone 2.5, 5, 10 mg Versus Placebo in the Treatment of Endometriosis
NCT02271958
COMPLETED
PHASE2/PHASE3
A Phase II Randomized Open Label Study of KLH-2109 in Patients With Endometriosis
NCT01629420
COMPLETED
PHASE2
A Study to Investigate Efficacy and Safety of OG-6219 BID in 3 Dose Levels Compared With Placebo in Participants Aged 18 to 49 With Moderate to Severe Endometriosis-related Pain
NCT05560646
COMPLETED
PHASE2
A Study to Assess the Efficacy and Safety of HMI-115 in Subjects With Endometriosis-Associated Pain
NCT05101317
COMPLETED
PHASE2
Evaluation of Therapeutic Effect and Safety of Mifepristone in the Treatment of Adenomyosis
NCT03520439
COMPLETED
PHASE2/PHASE3
Ear Electro-stimulation for Chronic Pelvic Pain
NCT01345331
COMPLETED
NA
Acupuncture for Pain of Endometriosis
NCT03125304
COMPLETED
NA
Study Evaluating ERB-041 in Endometriosis in Reproductive-Age Women
NCT00110487
COMPLETED
PHASE2
A Randomized Open Label Study of KLH-2109 in Patients With Endometriosis(1)
NCT01395940
COMPLETED
PHASE2
The Pharmacokinetic(PK)/Pharmacodynamics(PD) Study of SHR7280 Tablets in Premenopausal Subjects With Endometriosis.
NCT04417972
COMPLETED
PHASE1/PHASE2
Efficacy and Safety of BG2109 in Chinese Subjects With Endometriosis
NCT05894135
UNKNOWN
PHASE3
Clinical Trial the Use of Levonorgestrel-releasing Intrauterine System Versus Etonogestrel Implant in Endometriosis
NCT02480647
COMPLETED
PHASE4
Estradiol-mediated Inflammation and Central Sensitization in the Pathophysiology of Endometriosis-associated Pelvic Pain
NCT07100782
RECRUITING
PHASE3
A Study of Women Receiving Standard of Care (SOC) for the Treatment of Pelvic Pain Due to Suspected or Confirmed Endometriosis and the Impact on the Disease or Symptom Progression.
NCT04140175
TERMINATED
Effect of KYG0395 on Primary Dysmenorrhea
NCT01588236
COMPLETED
PHASE2
Evaluate the Efficacy and Safety of HMI-115 in Women With Moderate to Severe Endometriosis-associated Pain
NCT07318688
NOT_YET_RECRUITING
PHASE3
Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
NCT03241888
COMPLETED
PHASE2/PHASE3
Levonorgestrel-releasing Intrauterine System for the Treatment of Symptomatic Adenomyosis
NCT03027648
COMPLETED
NA
Late Phase II Clinical Study of KLH-2109 in Patients With Endometriosis
NCT02778919
COMPLETED
PHASE2
Study Evaluating the Safety and Efficacy of ERB-041 on Reduction of Symptoms Associated With Endometriosis in Reproductive-Aged Women
NCT00318500
COMPLETED
PHASE2
Global Study of Women's Health
NCT00849173
COMPLETED