Fatty Liver
Conditions
Keywords
nonalcoholic fatty liver disease
Brief summary
The purpose of this study is to find out if Metformin is safe and useful in the treatment of NAFLD.
Detailed description
NAFLD is a poorly understood disease which may cause an enlarged liver, abnormal liver test results, and scarring of the liver. It may occur more often in people with obesity, high levels of cholesterol (blood fats), diabetes (high blood sugar), or the insulin resistance syndrome (where a person's body does not respond to the hormone insulin which helps keep blood sugar levels normal). Currently, no effective drug treatment for NAFLD exists. There is increasing evidence that NAFLD may be a condition due to a problem with metabolism (the way your body uses energy). Previous studies have shown that high glucose (sugar) levels may play an important role in the development of fatty liver disease. Medications that decrease your natural glucose level may reduce the amount of fat in the liver and, therefore, might be useful in the treatment of NAFLD. Metformin, a drug approved by the U.S. Food and Drug Administration (FDA) for use in patients with diabetes, has been shown to improve fatty liver in animals and in a small number of human beings.
Interventions
DRUGGlucophage (Metformin)
metformin XR 2000 mg daily for 12 months
DRUGPlacebo
placebo 2000 mg daily for 12 months
Sponsors
Duke University
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
* biopsy-proven NAFLD, determined within 12 months of study initiation
Exclusion criteria
* \> 20 grams of alcohol/day * impaired oral glucose tolerance test * known diagnosis of diabetes mellitus * hepatitis C infection * cirrhosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Study Endpoints Will Include Measurements of Insulin Sensitivity, Hepatic Insulin Clearance, and Altered Parameters of Lipid Metabolism, Changes in the Histological Features That Define NAFLD, and Quantitative Measurements of Visceral and Peripheral Fat. | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Determine if Metformin Improves the Altered Parameters of Lipid Metabolism as Compared to Placebo. | 24 months |
| Tests the Postulate That Metformin Will Improve Insulin Sensitivity in NAFLD. Also Test the Postulate That Improving IR (Insulin Resistance) With an Insulin Sensitizing Agent Will Improve Biochemical and Histological Features of NAFLD. | 24 months |
| Measure the Differential Effects of IR and Lipid Metabolism on Peripheral Mononuclear Cell (PBMC) Inflammatory Response and the Associated Hepatocyte Mitochondrial Ultrastructure and Measures of Oxidative Stress | 24 months |
Countries
United States
Participant flow
Recruitment details
11 subjects signed consent to participate. 2 subjects were screen failures. 9 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Metformin Metformin XR 2000 mg daily
Glucophage (Metformin): metformin XR 2000 mg daily for 12 months | 4 |
| Placebo Placebo capsule
Placebo: placebo 2000 mg daily for 12 months | 5 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Metformin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment United States | 4 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 0 / 4 | 2 / 5 |
Outcome results
Primary
Study Endpoints Will Include Measurements of Insulin Sensitivity, Hepatic Insulin Clearance, and Altered Parameters of Lipid Metabolism, Changes in the Histological Features That Define NAFLD, and Quantitative Measurements of Visceral and Peripheral Fat.
Time frame: 24 months
Population: Study was terminated early due to difficulties with enrollment. No outcome measures were assessed.
Secondary
Determine if Metformin Improves the Altered Parameters of Lipid Metabolism as Compared to Placebo.
Time frame: 24 months
Population: Study was terminated early due to difficulties with enrollment. No outcome measures were assessed.
Secondary
Measure the Differential Effects of IR and Lipid Metabolism on Peripheral Mononuclear Cell (PBMC) Inflammatory Response and the Associated Hepatocyte Mitochondrial Ultrastructure and Measures of Oxidative Stress
Time frame: 24 months
Population: Study was terminated early due to difficulties with enrollment. No outcome measures were assessed.
Secondary
Tests the Postulate That Metformin Will Improve Insulin Sensitivity in NAFLD. Also Test the Postulate That Improving IR (Insulin Resistance) With an Insulin Sensitizing Agent Will Improve Biochemical and Histological Features of NAFLD.
Time frame: 24 months
Population: Study was terminated early due to difficulties with enrollment. No outcome measures were assessed.