Estrogen Administration for the Treatment of NASH in Postmenopausal Women

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.

Study Overview

• Status: Recruiting
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Estradiol patch; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anu Gerweck, NP; Phone Number: 617-724-1837; Email: avgerweck@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Estradiol patch; The patch will provide 100mcg of estradiol daily.
Placebo Comparator: Placebo; Placebo patch (containing no estradiol) Women with an intact uterus will also receive vaginal placebo capsules (containing no progesterone)	Drug: Placebo; Placebo patch will contain no estradiol.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Karen K. Miller, MD, Massachsuetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2021
• Primary Completion (Anticipated): May 31, 2027
• Study Completion (Anticipated): May 31, 2027

Study Registration Dates

• First Submitted: April 3, 2021
• First Submitted That Met QC Criteria: April 3, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 2021P001506

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes