Metformin for the Treatment of Endometrial Hyperplasia

Study Overview
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Brief Summary
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The purpose of this study is to see if metformin will be effective in making endometrial hyperplasia without atypia better by returning the tissue to a normal state.

Detailed Description
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This is a multi-institutional pilot clinical trial designed to estimate the response rate and safety of metformin for the treatment of simple and complex endometrial hyperplasia (EH) without atypia. Enrollment of patients will occur at UNC-Chapel Hill and Southern Pines Women's Health Center. Fifteen patients will be enrolled over the course of 1 year. Metformin will be initiated at 850 mg orally once daily, and titrated up to twice daily over a minimum of 1 months time. Treatment will last 12 weeks and then patients will undergo repeat endometrial biopsy to assess for regression or persistence of EH.

Official Title
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Metformin for the Treatment of Endometrial Hyperplasia

Conditions
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Endometrial Hyperplasia, Endometrial Hyperplasia Without Atypia

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be between the ages of 18-75 years old Have a confirmed diagnosis of endometrial hyperplasia without atypia based upon endometrial biopsy Have no contraindications to short-term metformin therapy Have a creatinine clearance of ≥ 90 ml/min, as calculated by the Cockroft-Gault formula Have normal serum transaminase values (AST and ALT) Need to be able to undergo metformin treatment for a duration of 12 weeks prior to repeat endometrial biopsy Exclusion Criteria: Are currently taking metformin or have taken metformin in the past 6 months or have a history of an allergic reaction or intolerance at any time to metformin Have a history of liver or renal dysfunction. Have a random glucose of ≤ 65 or ≥ 200 Have a recent history of alcoholism. Former alcoholics who have abstained from alcohol for 5 years or more may be enrolled in this study. Have a history of vitamin B12 deficiency Are pregnant Are currently taking insulin Are taking a drug that may significantly interact or influence the metabolism of metformin In the opinion of the investigator, the patient is felt not to be appropriate for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Metformin once daily for 4 weeks (weeks 1-4) and then twice daily for 8 weeks (weeks 5-12). | Drug: Metformin<br>* 850 mg of metformin taken once daily by mouth for 4 weeks (weeks 1-4) and then twice daily by mouth for 8 weeks (weeks 5-12).<br>* Other names: Riomet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Evaluation of hyperplasia resolution by comparison of pre- and post-treatment endometrial biopsies. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity evaluation | Number of subjects who experience side effects | 12 weeks | 
| Patient Compliance | Percentage of patients successfully completing metformin therapy. | 12 weeks | 
| Potential molecular markers in response to treatment with Metformin | Compare changes in potential biomarkers, including metabolic factors and molecular markers of downstream targets of the metformin/mTOR signaling pathway, before and after metformin treatment. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrial hyperplasia, Uterus, Pilot, Metformin