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Estrogen Administration for the Treatment of NASH in Postmenopausal Women

Primary Purpose

NASH - Nonalcoholic Steatohepatitis

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Estradiol patch
Placebo
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NASH - Nonalcoholic Steatohepatitis

Eligibility Criteria

45 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Estradiol

Placebo

Arm Description

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

Outcomes

Primary Outcome Measures

Liver fibrosis
Reduction in degree of liver fibrosis
Liver fat
Reduction in amount of fat in the liver

Secondary Outcome Measures

Full Information

First Posted
April 3, 2021
Last Updated
April 7, 2023
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04833140
Brief Title
Estrogen Administration for the Treatment of NASH in Postmenopausal Women
Official Title
Estrogen Administration for the Treatment of NASH in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 2, 2021 (Actual)
Primary Completion Date
May 31, 2027 (Anticipated)
Study Completion Date
May 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NASH - Nonalcoholic Steatohepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Estradiol
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo patch (containing no estradiol) Women with an intact uterus will also receive vaginal placebo capsules (containing no progesterone)
Intervention Type
Drug
Intervention Name(s)
Estradiol patch
Intervention Description
The patch will provide 100mcg of estradiol daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo patch will contain no estradiol.
Primary Outcome Measure Information:
Title
Liver fibrosis
Description
Reduction in degree of liver fibrosis
Time Frame
12 months
Title
Liver fat
Description
Reduction in amount of fat in the liver
Time Frame
12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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 Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anu Gerweck, NP
Phone
617-724-1837
Email
avgerweck@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen K. Miller, MD
Organizational Affiliation
Massachsuetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

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Estrogen Administration for the Treatment of NASH in Postmenopausal Women

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