NASH - Nonalcoholic Steatohepatitis
Conditions
Brief summary
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 a particularly high risk of NASH due to their lack of estrogen. This study will examine the effect of estradiol on hepatic fat and fibrosis in post-menopausal women with NASH.
Interventions
DRUGEstradiol patch
The patch will provide 100mcg of estradiol daily.
DRUGPlacebo
Placebo patch will contain no estradiol.
Sponsors
Massachusetts General Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic fat | 12 months | Change in percentage of hepatic fat |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic fibrosis | 12 months | Decrease in hepatic fibrosis by ≥1 stage |
| Non-alcoholic fatty liver disease activity score | 12 months | Change in non-alcoholic fatty liver disease activity score (minimum value: 0; maximum value: 8; lower scores indicate less disease activity) without progression of fibrosis stage |
| Whole liver transcriptome profile | 12 months | Change in whole liver transcriptome profile |
| Intrahepatic immune cell profiles | 12 months | Change in intrahepatic immune cell profile |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKaren K. Miller, MD
Massachusetts General Hospital
Outcome results
None listed