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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a non-hormonal medication, can reduce pelvic pain in young women with endometriosis. The researchers aim to determine if metformin is more effective than a placebo (a pill with no active ingredients) in easing pain and affecting inflammation over six months. Participants will take either metformin or a placebo daily and record their symptoms in a diary. Women diagnosed with endometriosis through surgery, currently experiencing pelvic pain, and who have been on hormonal therapy for at least two months may be suitable for this trial. As a Phase 2 trial, this research measures metformin's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research has shown that metformin is generally safe for use. It often manages diabetes and studies have found it to be well-tolerated. For instance, women taking metformin for other health issues usually respond well to the treatment, although some might experience side effects. Metformin has been safely used in doses from 500 mg to 2.5 g per day during pregnancy to manage gestational diabetes, indicating safety for both women and their unborn babies.

Due to its common use and evidence from other conditions, metformin appears to be a promising option for treating pelvic pain related to endometriosis. While side effects can occur, many people use this medication without major problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometriosis?

Researchers are excited about using metformin for endometriosis because it offers a potential new approach to treating this condition. Unlike standard treatments such as hormonal therapies and pain relief medications, metformin is primarily known as a treatment for diabetes and works by improving insulin sensitivity and reducing inflammation. This unique mechanism could address the root causes of endometriosis differently, potentially offering relief for those who don't respond well to current options. Additionally, metformin is taken orally, making it an easy addition to a patient's daily routine.

What evidence suggests that metformin might be an effective treatment for endometriosis?

This trial will compare Metformin with a placebo to evaluate its effectiveness in treating endometriosis. Studies have shown that Metformin might help by reducing inflammation and the growth of endometrial cells, potentially shrinking abnormal tissue growth and lessening pain. Research in mice suggests Metformin can also reduce oxidative stress and scarring in endometriosis. Additionally, Metformin may lower the formation of new blood vessels that support endometriosis growth. These findings suggest Metformin could be an effective non-hormonal treatment option for managing endometriosis-related pain. ^{1 2 3 6 7}

Who Is on the Research Team?

Jessica Shim, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8833654/

Metformin as a Potential Treatment Option for Endometriosis To summarize, metformin can reduce angiogenesis, inflammation, invasion, and adhesion and may cause regression of endometrial lesions. Insulin ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06611501

Glycemic Regulation as Endometriosis Adjunct Treatment 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1472648324006631

ARTICLE Metformin reverses infertility in a mouse model of ... Conclusions. These results indicate that application of metformin can alleviate oxidative stress and mitigate fibrosis in endometriosis lesions in a murine ...

4. ajol.info ajol.info/index.php/tjpr/article/view/248984/235450

A systematic review and meta-analysis Preclinical studies have demonstrated that metformin can inhibit the proliferation and invasion of endometrial cells, reduce the formation of endometriotic ...

5. mdpi.com mdpi.com/2227-9059/10/11/2782

Metformin Prevents Endothelial Dysfunction in ... In summary, metformin diminished endometriosis-associated endothelial dysfunction but did not mitigate the increase in NF-kB expression and cardiac fibrosis in ...

6. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(24)00007-6/fulltext

Associations of metformin therapy treatment with ... The pooled data showed that metformin use was associated with an increased risk of EC in T2DM (HR = 1. 17, 95% CI 1.09–1.26, P < 0.0001) (Fig. 2) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11064888/

Metformin for endometrial hyperplasia - PMC - PubMed Central Although women taking metformin may experience side effects, treatment is usually well tolerated.