Estrogen Administration for the Treatment of NASH in Postmenopausal Women

NCT04833140 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2021P001506
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Liver fat

  Reduction in amount of fat in the liver

  12 months

Study Arms (2)

Estradiol

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Estradiol patch DRUG

The patch will provide 100mcg of estradiol daily.

Estradiol

Placebo DRUG

Placebo patch will contain no estradiol.

Placebo

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Ortho Evra

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Karen K. Miller, MD

  Massachsuetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caitlin Dobbie, NP

CONTACT

617-643-8635; cdobbie@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Neuroendocrine Unit, Massachusetts General Hospital

Study Record Dates

• First Submitted: April 3, 2021
• First Posted: April 6, 2021
• Study Start: December 2, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)