NASH - Nonalcoholic SteatohepatitisPhase 3NCT04833140
Estrogen Administration for the Treatment of NASH in Postmenopausal Women
A Phase 3 study testing Estradiol patch in people with NASH - Nonalcoholic Steatohepatitis, run by Massachusetts General Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 70 years, women only
- Conditions the study is for
- NASH - Nonalcoholic Steatohepatitis
- What is being tested?
- Estradiol patch
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Dec 2021to 9 Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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 a particularly high risk of NASH due to their lack of estrogen. This study will examine the effect of estradiol on hepatic fat and fibrosis in post-menopausal women with NASH.
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Being tested
- Estradiol patch, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol patchDrug
The patch will provide 100mcg of estradiol daily.
PlaceboDrug
Placebo patch will contain no estradiol.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic fat
Change in percentage of hepatic fat
Measured: 12 months
Secondary outcomes (4)
Hepatic fibrosis
Decrease in hepatic fibrosis by ≥1 stage
Measured: 12 months
Non-alcoholic fatty liver disease activity score
Change in non-alcoholic fatty liver disease activity score (minimum value: 0; maximum value: 8; lower scores indicate less disease activity) without progression of fibrosis stage
Measured: 12 months
Whole liver transcriptome profile
Change in whole liver transcriptome profile
Measured: 12 months
Intrahepatic immune cell profiles
Change in intrahepatic immune cell profile
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study start2 Dec 2021
- Primary completion9 Jul 2027 (estimated)
- Study completion9 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NASH - Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Karen Klahr Miller, MD, Massachusetts General Hospital
- Investigators
- Karen K. Miller, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04833140
- Sponsor's protocol ID
- 2021P001506
- Other IDs
- 1R01DK126955-01A1
- Status last verified
- Aug 2026
- First submitted
- 3 Apr 2021
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estrogen Administration for the Treatment of NASH in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT04833140
- Acronym / sponsor ID
- 2021P001506
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 2 Dec 2021 (actual)
- Primary completion
- 9 Jul 2027 (estimated)
- Study completion
- 9 Jul 2027 (estimated)
- First posted
- 6 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 a particularly high risk of NASH due to their lack of estrogen. This study will examine the effect of estradiol on hepatic fat and fibrosis in post-menopausal women with NASH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Estradiol | Active comparator | Drug: Estradiol patchEstradiol 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 | Placebo comparator | Drug: PlaceboPlacebo patch (containing no estradiol) Women with an intact uterus will also receive vaginal placebo capsules (containing no progesterone) |
Who may qualify
- Ages
- 45 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estradiol patchThe patch will provide 100mcg of estradiol daily. | Drug | Estradiol |
| PlaceboPlacebo patch will contain no estradiol. | Drug | Placebo |
Primary outcome
Hepatic fat
Time frame: 12 months
Change in percentage of hepatic fat
4 secondary outcomes
Hepatic fibrosis
Time frame: 12 months
Non-alcoholic fatty liver disease activity score
Time frame: 12 months
Whole liver transcriptome profile
Time frame: 12 months
Intrahepatic immune cell profiles
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen K. Miller, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Estradiol patch in people with NASH - Nonalcoholic Steatohepatitis, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic fat (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.