Metformin for Endometriosis

(GREAT Trial)

Overseen By Jessica Shim, MD

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Boston Children's Hospital

Must be taking: Hormonal therapy

Disqualifiers: Diabetes, Severe renal dysfunction, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

14 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it requires participants to have been on a consistent hormonal therapy for endometriosis for at least 2 months before joining, so you may need to continue that treatment.

What evidence supports the effectiveness of the drug metformin for treating endometriosis?

Research shows that metformin can reduce the growth of endometriotic tissue and improve conditions for embryo implantation by affecting certain genes and proteins involved in inflammation and tissue growth. This suggests metformin might help alleviate symptoms of endometriosis and potentially improve fertility. ^{1 2 3 4 5}

Is Metformin safe for humans?

Metformin is generally considered safe for humans when used as directed, with common side effects including stomach issues and a decrease in vitamin B12 absorption. Rarely, it can cause liver problems and lactic acidosis (a buildup of lactic acid in the blood) in people with severe kidney issues. ^{6 7 8 9 10}

How does the drug metformin differ from other treatments for endometriosis?

Metformin is unique in treating endometriosis because it not only reduces inflammation and abnormal tissue growth but also improves insulin sensitivity and regulates hormones, which are key factors in the condition. Unlike other treatments, metformin also enhances fertility by improving the environment of the uterus, making it a promising option for women with endometriosis who wish to conceive. ^{1 3 4 11 12}

What is the purpose of this trial?

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

Research Team

Jessica Shim, MD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for young women with endometriosis experiencing pelvic pain. Participants will take a daily dose of either metformin or placebo for 6 months and visit the clinic three times. They must keep a symptom diary. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I have been on hormonal therapy for endometriosis for at least 2 months.

I have had pelvic pain rated 3 or higher for at least 2 months.

I am a woman diagnosed with endometriosis through surgery.

Exclusion Criteria

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

Inability to read English

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take metformin or placebo daily for 6 months to assess its effect on pelvic pain and inflammatory markers

6 months

3 visits (in-person) at baseline, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Metformin Hydrochloride

Trial Overview The study tests if metformin, a non-hormonal treatment, can alleviate pelvic pain in endometriosis better than a placebo. It also examines whether metformin affects inflammatory markers over the course of treatment.

Participant Groups

Group I: Metformin Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Findings from Research

In a study of 130 patients with type 2 diabetes treated with Metformin Hydrochloride, gastrointestinal adverse effects were the most common, with diarrhea affecting 30.77% of patients and leading to treatment discontinuation in 3.85%.

No cases of serious complications like lactic acidosis or allergic reactions were reported, indicating that while Metformin is generally safe, monitoring for digestive issues is important in managing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cross-Sectional Study on Adverse Effects of Metformin Hydrochloride on 130 Patients Type 2 Diabetic Admitted to Medical Center and Diabetes Home of Sidi Bel-Abbès]. Sakouhi, M., Matmour, D., Belakhdar, K., et al.[2023]

Metformin is an effective oral medication for treating non-insulin-dependent diabetes mellitus (type II diabetes) and does not cause hypoglycemia, which is a common side effect of other diabetes medications like sulfonylureas.

The drug is considered safe when proper precautions are taken, including monitoring liver and kidney function, and it has gained widespread use internationally, recently receiving FDA approval under the brand name Glucophage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. Tanja, JJ., Langlass, TM.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. [2015]

2. Turkey pubmed.ncbi.nlm.nih.gov

Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma. [2018]

6. France pubmed.ncbi.nlm.nih.gov

[Cross-Sectional Study on Adverse Effects of Metformin Hydrochloride on 130 Patients Type 2 Diabetic Admitted to Medical Center and Diabetes Home of Sidi Bel-Abbès]. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Possible metformin-induced hepatotoxicity. [2016]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular Protection by Metformin: Latest Advances in Basic and Clinical Research. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. [2013]

10. Italy pubmed.ncbi.nlm.nih.gov

[Metformin and kidney]. [2017]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin as a Potential Treatment Option for Endometriosis. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Effects of metformin, letrozole and atorvastatin on inflammation and apoptosis in experimental peritoneal and ovarian endometriosis in the rat. [2022]