NCT04833140

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 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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at below P25 for phase_3

Timeline
9mo left

Started Dec 2021

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress86%
Dec 2021Jul 2027

First Submitted

Initial submission to the registry

April 3, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 6, 2021

Completed
8 months until next milestone

Study Start

First participant enrolled

December 2, 2021

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 9, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 9, 2027

Last Updated

August 7, 2026

Status Verified

August 1, 2026

Enrollment Period

5.6 years

First QC Date

April 3, 2021

Last Update Submit

August 5, 2026

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

  • Hepatic fat

    Change in percentage of hepatic fat

    12 months

Secondary Outcomes (4)

  • Hepatic fibrosis

    12 months

  • Non-alcoholic fatty liver disease activity score

    12 months

  • Whole liver transcriptome profile

    12 months

  • Intrahepatic immune cell profiles

    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 patchDRUG

The patch will provide 100mcg of estradiol daily.

Estradiol
PlaceboDRUG

Placebo patch will contain no estradiol.

Placebo

Eligibility Criteria

Age45 Years - 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Ortho Evra

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System Diseases

Study Officials

  • Karen K. Miller, MD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR

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)

July 9, 2027

Study Completion (Estimated)

July 9, 2027

Last Updated

August 7, 2026

Record last verified: 2026-08

Locations

US(1)