Estrogen Administration for the Treatment of NASH in Postmenopausal Women
Purpose
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.
Condition
- NASH - Nonalcoholic Steatohepatitis
Eligibility
- Eligible Ages
- Between 45 Years and 70 Years
- Eligible Genders
- Female
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Active Comparator Estradiol |
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 |
|
Placebo Comparator Placebo |
Placebo patch (containing no estradiol) Women with an intact uterus will also receive vaginal placebo capsules (containing no progesterone) |
|
Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Massachusetts General Hospital