Estrogen Therapy as Prevention in the Progression of Aneurysm (EPPA) Trial

Study Overview
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Brief Summary
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This study aims to determine if hormone replacement therapy, given during perimenopause may prevent the progression of saccular cerebral aneurysms.

Detailed Description
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This is a prospective, randomized, placebo-control trial to test the effect of estradiol in the prevention of progression of cerebral aneurysms. To evaluate the effect, each subject will be treated with either oral estradiol or placebo for 6 months. Subjects will be randomly assigned to 1 of 2 groups as follows: Double Blind Treatment Group Open-Label Regimen A1 1 mg Estradiol daily for 180 days B1 Placebo for 180 days Each group will be given oral Progesterone (3300 mg) for 10 days at the end of 90 days regardless of menstrual pattern. Subjects will be asked to keep a menstrual calendar throughout the trial. Serum markers will be drawn at baseline and every 90 days with the results blinded until the end of the trial. Magnetic resonance angiography (MRA) studies of the brain will be performed at month 6.

Official Title
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Estrogen Therapy as Prevention in the Progression of Aneurysm

Conditions
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Cerebral Aneurysm, Menopause, Treatment

Intervention / Treatment
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* Drug: Estradiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy women, 40-52 years of age. At least one documented saccular intracranial cerebral aneurysm detected via catheter angiography, magnetic resonance angiography or computed tomography angiography. Clinical diagnosis of perimenopause, defined as regular or irregular menses with or without vasomotor symptoms. Exclusion Criteria: Known or suspected estrogen-dependent neoplasia. Endometrial proliferation, hyperplasia, or malignancy at screening. Known hypersensitivity to estrogens, progestins. History of myocardial infarction, ischemic heart disease, lipid disorder, or congestive heart failure. Known or suspected pregnancy, or recent breast feeding (within 6 months).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 52 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estradiol Daily<br>1 mg Estradiol daily for 180 days. | Drug: Estradiol<br> <br> |
| Placebo Comparator: Placebo<br>Placebo for 180 days. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of low dose estradiol on a panel of serum markers. | Parallel design double-blind placebo controlled trial to assess the effect of low dose estradiol on serum lipoprotein (a), serum elastase, and homocysteine. | Change in levels of serum markers from baseline and six months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic change in the cerebral vasculature after treatment. |  | From date of randomization to six months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracranial Aneurysm, Estradiol