Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis
Conditions
Keywords
Aspirin, Liver Disease, Anti-inflammatory
Brief summary
Nonalcoholic fatty liver disease (NAFLD), defined by fatty infiltration of the liver in the absence of excess alcohol consumption, affects an estimated 30% of adults in the United States. A proportion of people with NAFLD will develop progressive, inflammatory nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and liver failure. NAFLD is expected to be the most common indication for liver transplantation by the year 2020. We hypothesize that among adults with NAFLD, aspirin will reduce intrahepatic lipid content, as quantified by 1H magnetic resonance spectroscopy (1H-MRS).
Interventions
DRUGAspirin 81 mg
Aspirin 81mg tablets will be given once daily, for the duration of the clinical trial.
DRUGPlacebo oral tablet
Identical, blinded placebo tablets will be given once daily, for the duration of the clinical trial.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Ages 18 to 70 years * NAFLD, defined by confirmed hepatic steatosis by imaging or by liver biopsy, in the absence of other causes of hepatic steatosis or significant alcohol consumption. If liver imaging or biopsy has not been performed clinically, liver ultrasound assessment will be performed as part of the screening visit. * Early-stage liver fibrosis, defined as fibrosis less than or equal to Fibrosis Stage 3 (F3), confirmed by either (1) a recent liver biopsy or (2) a recent elastography / Fibroscan study. If no recent biopsy or elastography/Fibroscan have been performed, a Fibroscan will be performed as part of the screening visit.
Exclusion criteria
* Liver fibrosis stage \> 3 * Current aspirin use * Contraindications to aspirin use * Contraindications to magnetic resonance imaging (MRI) * Pregnancy or desire to become pregnant * Breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Intrahepatic Lipid Content, by 1H-MRS | 6 months | Absolute percentage change in intrahepatic lipid content, quantified by 1H-MRS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change in Intrahepatic Lipid Content | 6 months | Relative percentage point change in intrahepatic lipid content |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin Low-dose (81mg) aspirin tablets
Aspirin 81 mg: Aspirin 81mg tablets will be given once daily, for the duration of the clinical trial. | 40 |
| Placebo Placebo tablets
Placebo oral tablet: Identical, blinded placebo tablets will be given once daily, for the duration of the clinical trial. | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Aspirin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 36 Participants | 73 Participants |
| Age, Continuous | 46.6 years | 49.3 years | 47.9 years |
| Baseline hepatic lipid content (%) by 1H_MRS | 39.1 percentage of hepatic lipid content STANDARD_DEVIATION 26.1 | 31.4 percentage of hepatic lipid content STANDARD_DEVIATION 24.8 | 35.0 percentage of hepatic lipid content STANDARD_DEVIATION 20.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American, non-Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized White, non-Hispanic | 30 Participants | 33 Participants | 63 Participants |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 21 Participants | 23 Participants | 44 Participants |
| Sex: Female, Male Male | 19 Participants | 17 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 12 / 40 | 12 / 40 |
| serious Total, serious adverse events | 1 / 40 | 1 / 40 |
Outcome results
Primary
Absolute Change in Intrahepatic Lipid Content, by 1H-MRS
Absolute percentage change in intrahepatic lipid content, quantified by 1H-MRS
Time frame: 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Aspirin | Absolute Change in Intrahepatic Lipid Content, by 1H-MRS | -6.6 Mean absolute percentage change |
| Placebo | Absolute Change in Intrahepatic Lipid Content, by 1H-MRS | 3.6 Mean absolute percentage change |
Secondary
Relative Change in Intrahepatic Lipid Content
Relative percentage point change in intrahepatic lipid content
Time frame: 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Aspirin | Relative Change in Intrahepatic Lipid Content | -8.8 Mean percentage point change |
| Placebo | Relative Change in Intrahepatic Lipid Content | 30.0 Mean percentage point change |