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
About this trial
This is an interventional treatment trial for NASH - Nonalcoholic Steatohepatitis
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
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
NCT ID
NCT04833140
First Posted
April 3, 2021
Last Updated
April 7, 2023
Sponsor
Massachusetts General Hospital
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
Learn more about this trial
Estrogen Administration for the Treatment of NASH in Postmenopausal Women
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