Estrogen Administration for the Treatment of NASH in Postmenopausal Women

NCT ID: NCT04833140

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-02
• Study Completion Date: 2027-05-31

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 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.

Conditions

NASH - Nonalcoholic Steatohepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Estradiol patch

Intervention Type: DRUG

The patch will provide 100mcg of estradiol daily.

Placebo

Placebo patch (containing no estradiol) Women with an intact uterus will also receive vaginal placebo capsules (containing no progesterone)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo patch will contain no estradiol.

Interventions

Estradiol patch

The patch will provide 100mcg of estradiol daily.

Intervention Type: DRUG

Placebo

Placebo patch will contain no estradiol.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Karen Klahr Miller, MD

Chief, Neuroendocrine Unit, Massachusetts General Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karen K. Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Massachsuetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Caitlin Dobbie, NP

Role: CONTACT

cdobbie@mgb.org

617-643-8635

Other Identifiers

2021P001506

Identifier Type: -

Identifier Source: org_study_id