Estrogen Administration for the Treatment of NASH in Postmenopausal Women

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic in the United States. Despite this, the treatment options remain limited. Preclinical and preliminary clinical data suggest that estrogen deficiency plays an important role in the pathology of steatosis, inflammation and fibrosis in non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD. Post-menopausal women are a growing population with particularly high risk of NASH due to their lack of estrogen. This study will examine the effect of estradiol on hepatic fibrosis and fat in post-menopausal women with NASH.

Official Title
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Estrogen Administration for the Treatment of NASH in Postmenopausal Women

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Estradiol patch
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Postmenopausal women 45-70 years old NASH by biopsy or NAFLD by imaging within 6 months of screen Hepatitis C antibody and hepatitis B surface antigen negative Negative mammogram within 1 year Exclusion criteria: Heavy alcohol use Use of NASH pharmacotherapies within 12 months of study entry Known cirrhosis, stage 4 fibrosis on biopsy, or clinical evidence of cirrhosis or portal hypertension on imaging or exam Participation in NASH clinical trial within 6 months of study entry Chronic use of corticosteroids, methotrexate, amiodarone, or tamoxifen within 6 months of entry Known diagnosis of chronic liver disease other than NAFLD or found on biopsy Contraindication to liver biopsy including INR > 1.5, platelets < 50,000/mL, ascites, chronic anticoagulation (other than aspirin), biliary obstruction, peritonitis, inability to lie supine for 30 minutes Hgb < 10.0 g/dL or glomerular filtration rate < 60 mL/min Contraindications to estrogen therapy Any vaginal bleeding, including spotting, within the last year Active malignancy Severe chronic illness Use of estrogen or progesterone within a year of baseline visit Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Estradiol<br>Estradiol in the form of a transdermal patch 100 mcg daily (Vivelle-Dot generic). Women with an intact uterus will also receive progesterone (100 mg) in the form of a vaginal tablet (Endometrin, Ferring Pharmaceuticals, Inc.) inserted daily for endometrial protection | Drug: Estradiol patch<br>* The patch will provide 100mcg of estradiol daily.<br>|
| Placebo Comparator: Placebo<br>Placebo patch (containing no estradiol) Women with an intact uterus will also receive vaginal placebo capsules (containing no progesterone) | Drug: Placebo<br>* Placebo patch will contain no estradiol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver fibrosis | Reduction in degree of liver fibrosis | 12 months | 
| Liver fat | Reduction in amount of fat in the liver | 12 months |