Non-alcoholic Fatty Liver Disease
Conditions
Keywords
non-alcoholic fatty liver disease, obesity, fatty liver disease
Brief summary
The primary goal of this study is to provide a better understanding of: 1) the pathogenesis and pathophysiology of non-alcoholic fatty liver disease (NAFLD) in obese subjects, and 2) the effect of marked weight loss on the histologic and metabolic abnormalities associated with NAFLD. The following hypotheses will be tested: 1. obesity causes hepatic fat accumulation because of excessive fatty acid release from fat tissue and increased free fatty acid availability, 2. increased hepatic (liver) fat content causes insulin-resistant glucose (sugar) production by the liver and altered liver protein synthesis, 3. increased hepatic fat content causes increased lipid (fat) peroxidation, hepatic inflammation, necrosis and fibrosis, and 4. marked weight loss improves NAFLD once patients are weight stable.
Detailed description
Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD), which represents a spectrum of liver diseases. NAFLD is a major health problem in the US because of its high prevalence and causal relationship with serious liver abnormalities. However, the mechanism(s)responsible for developing NAFLD in obese persons and the effects on liver function are not known. This gap in knowledge has made it difficult to identify effective therapy. The results from these studies will lay the groundwork for the development of novel therapeutic interventions for NAFLD in obese patients.
Interventions
DRUGNiacin
Subjects randomized to Niacin therapy will be treated with Niacin at night for 16 wks to reduce plasma free fatty acid concentrations. The dose of medication will be gradually increased: 500 mg/day during week 1, 1000 mg/day during week 2, 1500 mg/day during week 3, and 2000mg/day during weeks 4-16.
DRUGfenofibrate
Subjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks.
DRUGplacebo
Subjects randomized to placebo will be treated with one placebo pill per day for eight weeks.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
All * 18 - 45 years old * Class I obesity, i.e. Body Mass Index (BMI) between 30 and 45. * weight less than 300 lbs.
Exclusion criteria
* Active or previous infection with hepatitis B or C, as well as other liver disease. * History of alcohol abuse * Diabetes * Medications that cause liver damage or steatosis. * Women who are pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hepatic Insulin Sensitivity Index | baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) | Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index (HISI) is measured as the reciprocal of glucose rate of appearance \[10000/(μmol/min)\] multiplied by insulin concentration\[mU/L\]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated. |
| Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion. | baseline cross-sectional data pre and post nine hour euglycemic clamp | A precise measure of the ability of insulin to stimulate glucose uptake by skeletal muscle. Skeletal muscle insulin sensitivity, measured as the increase from baseline in skeletal muscle glucose uptake during insulin infusion(percentage)as part of a nine hour euglycemic hyperinsulinemic clamp study. |
| Adipose Tissue Insulin Sensitivity | baseline cross-sectional data pre and post nine hour euglycemic clamp | The ability of insulin to suppress the release of fatty acids from adipose tissue: Adipose tissue insulin sensitivity, measured as the suppression from baseline of free fatty acid release from adipose tissue (lipolysis) during insulin infusion as part of a nine hour euglycemic hyperinsulinemic clamp study. |
| Hepatic Fat Content for Fenofibrate and Niacin Groups | baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin) | Hepatic fat content as measured by magnetic resonance spectroscopy. A PRESS sequence was used. The results from three 10 cubic centimeter voxels positioned within the liver were averaged. The measure is a ratio of triglyceride signal to total signal. |
| Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups | baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin) | The baseline and post-treatment measures of adipose tissue insulin sensitivity (ATIS) were compared. ATIS at both timepoints is the suppression from fasting levels of free fatty acid release from adipose tissue (lipolysis) during an insulin infusion as part of a euglycemic clamp study. It is the percent decrease from time zero to the end of the nine hour euglycemic hyperinsulinemic clamp |
| Change From Baseline in Skeletal Muscle Insulin Sensitivity | baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) | Changes in skeletal muscle insulin sensitivity (SMIS). SMIS was measured as the increase in skeletal muscle glucose uptake from time zero to the end of a nine hour euglycemic clamp and insulin infusion study. This increase is the percentage change from time zero to end of insulin infusion at nine hours. |
| Hepatic Insulin Sensitivity Index (HISI) | baseline cross-sectional data | Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index(HISI) is the reciprocal of glucose rate of appearance \[10000/(μmol/min)\] multiplied by insulin concentration\[mU/L\]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate | baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin) | VLDL-apolipoprotein B (apoB) concentrations were measured as part of a VLDL metabolism study utilizing stable isotope tracers. VLDL apoB production rate, a measure of hepatic secretion of VLDL-apolipoproteinB-100 per liter of plasma per minute. |
| Change From Baseline in VLDL-Tg Clearance Rate | baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) | Very low density lipoprotein triglyceride (VLDL-Tg) clearance rate, a measure of VLDL-triglyceride removal from plasma per minute. |
| Change From Baseline in VLDL-Tg Production Rate | baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) | VLDL-TG production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute. |
| Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration | baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) | Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg) |
| Very Low Density Lipoprotein - Triglyceride Production Rate | baseline cross-sectional data | Very low density lipoprotein triglyceride (VLDL-TG) production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute (μmol/L/min). |
Countries
United States
Participant flow
Recruitment details
Beginning and ending recruitment dates: Beginning - 10/20/04; Ending - 09/24/07. Recruitment occurred only at Washington University in St. Louis.
Pre-assignment details
We screened 138 subjects. 80 would-be participants failed the screening. This was often due to not having Non-alcoholic Fatty Liver Disease. Other subjects were excluded due to use of various medications or the presence of some excluded disease such as type 2 diabetes. Of the 58 that passed screening 51 chose to enroll in the study.
Participants by arm
| Arm | Count |
|---|---|
| Controls Subjects with normal intra-hepatic triglyceride content (defined by less than 10% lipid to water signal in magnetic resonance spectroscopy). | 17 |
| NAFLD Subjects diagnosed with Non-Alcoholic Fatty Liver Disease(NAFLD). Determination of NAFLD was by magnetic resonance spectroscopy of intra-hepatic triglyceride content (defined by greater than 10% lipid to water signal). This group included subjects later randomized into the NAFLD-Niacin, NAFLD-Fenofibrate, and NAFLD-no intervention arms. | 34 |
| Total | 51 |
Baseline characteristics
| Characteristic | Total | Controls | NAFLD |
|---|---|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 3 | 41 years STANDARD_DEVIATION 3 | 45 years STANDARD_DEVIATION 3 |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 0 participants | 0 participants | 0 participants |
| Age, Customized Between 18 and 65 years | 51 participants | 17 participants | 34 participants |
| Body Mass Index (BMI) | 36.19 kg/m^2 STANDARD_DEVIATION 4.57 | 35.11 kg/m^2 STANDARD_DEVIATION 4.33 | 36.73 kg/m^2 STANDARD_DEVIATION 4.66 |
| Body Weight | 102.7 kilograms STANDARD_DEVIATION 14.4 | 99.8 kilograms STANDARD_DEVIATION 11.6 | 104.1 kilograms STANDARD_DEVIATION 15.6 |
| fat as percentage of total body composition | 40.3 percentage of total body weight STANDARD_DEVIATION 6.4 | 42.1 percentage of total body weight STANDARD_DEVIATION 6.9 | 39.3 percentage of total body weight STANDARD_DEVIATION 6 |
| plasma glucose level | 95.4 mg/dl STANDARD_DEVIATION 7.8 | 94.2 mg/dl STANDARD_DEVIATION 6 | 96.0 mg/dl STANDARD_DEVIATION 8.6 |
| plasma insulin level | 17.9 mU/L STANDARD_DEVIATION 9.6 | 11.4 mU/L STANDARD_DEVIATION 4.5 | 21.2 mU/L STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 51 participants | 17 participants | 34 participants |
| Sex: Female, Male Female | 37 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 11 | 0 / 11 | 0 / 12 | 0 / 17 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 17 |
Outcome results
Primary
Adipose Tissue Insulin Sensitivity
The ability of insulin to suppress the release of fatty acids from adipose tissue: Adipose tissue insulin sensitivity, measured as the suppression from baseline of free fatty acid release from adipose tissue (lipolysis) during insulin infusion as part of a nine hour euglycemic hyperinsulinemic clamp study.
Time frame: baseline cross-sectional data pre and post nine hour euglycemic clamp
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAFLD | Adipose Tissue Insulin Sensitivity | 66 percent decrease | Standard Error 2 |
| Controls | Adipose Tissue Insulin Sensitivity | 75 percent decrease | Standard Error 1 |
Comparison: null hypothesis was that there would be no difference in adipose tissue insulin sensitivity due to IHTG levels.p-value: <0.002t-test, 2 sided
Primary
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
The baseline and post-treatment measures of adipose tissue insulin sensitivity (ATIS) were compared. ATIS at both timepoints is the suppression from fasting levels of free fatty acid release from adipose tissue (lipolysis) during an insulin infusion as part of a euglycemic clamp study. It is the percent decrease from time zero to the end of the nine hour euglycemic hyperinsulinemic clamp
Time frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups | Baseline | 68 percent decrease | Standard Error 4 |
| NAFLD | Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups | 8 weeks (fenofibrate) or 16 weeks (niacin) | 69 percent decrease | Standard Error 2 |
| Controls | Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups | 8 weeks (fenofibrate) or 16 weeks (niacin) | 35 percent decrease | Standard Error 10 |
| Controls | Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups | Baseline | 63 percent decrease | Standard Error 4 |
Comparison: Null hypothesis was that fenofibrate would not affect adipose tissue insulin sensitivity. We compare the baseline and post-treatment results for adipose tissue insulin sensitivity in the subjects who received fenofibrate.p-value: 0.768t-test, 2 sided
Comparison: Null hypothesis was that niacin would not affect adipose tissue insulin sensitivity. Here we compare the baseline and post-treatment adipose tissue insulin sensitivity results for subjects who received a 16 week course of niacinp-value: 0.019t-test, 2 sided
Primary
Change From Baseline in Hepatic Insulin Sensitivity Index
Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index (HISI) is measured as the reciprocal of glucose rate of appearance \[10000/(μmol/min)\] multiplied by insulin concentration\[mU/L\]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Change From Baseline in Hepatic Insulin Sensitivity Index | Baseline | 0.7 [10000/(μmol/min)x(mU/L)] | Standard Error 0.1 |
| NAFLD | Change From Baseline in Hepatic Insulin Sensitivity Index | 8 weeks (fenofibrate) or 16 weeks (niacin) | 0.8 [10000/(μmol/min)x(mU/L)] | Standard Error 0.1 |
| Controls | Change From Baseline in Hepatic Insulin Sensitivity Index | Baseline | 0.8 [10000/(μmol/min)x(mU/L)] | Standard Error 0.4 |
| Controls | Change From Baseline in Hepatic Insulin Sensitivity Index | 8 weeks (fenofibrate) or 16 weeks (niacin) | 0.5 [10000/(μmol/min)x(mU/L)] | Standard Error 0.1 |
Comparison: The null hypothesis was that fenofibrate would not affect hepatic insulin sensitivity. Here we compare the pre and post-treatment results of subjects receiving an 8 week course of fenofibrate.p-value: 0.419t-test, 2 sided
Comparison: The null hypothesis was that niacin would not affect skeletal muscle insulin sensitivity. Here we compare the pre and post-treatment results of subjects receiving a 16 week course of niacin.p-value: 0.018t-test, 2 sided
Primary
Change From Baseline in Skeletal Muscle Insulin Sensitivity
Changes in skeletal muscle insulin sensitivity (SMIS). SMIS was measured as the increase in skeletal muscle glucose uptake from time zero to the end of a nine hour euglycemic clamp and insulin infusion study. This increase is the percentage change from time zero to end of insulin infusion at nine hours.
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Change From Baseline in Skeletal Muscle Insulin Sensitivity | Baseline | 188 percent increase | Standard Error 36 |
| NAFLD | Change From Baseline in Skeletal Muscle Insulin Sensitivity | 8 weeks (fenofibrate) or 16 weeks (niacin) | 169 percent increase | Standard Error 28 |
| Controls | Change From Baseline in Skeletal Muscle Insulin Sensitivity | Baseline | 183 percent increase | Standard Error 22 |
| Controls | Change From Baseline in Skeletal Muscle Insulin Sensitivity | 8 weeks (fenofibrate) or 16 weeks (niacin) | 142 percent increase | Standard Error 26 |
Comparison: The null hypothesis was that fenofibrate would not affect skeletal muscle insulin sensitivity. Here we compare the pre and post-treatment results in subjects receiving an 8 week course of fenofibrate.p-value: 0.318t-test, 2 sided
Comparison: The null hypothesis was that niacin would not affect skeletal muscle insulin sensitivity. Here we compare the pre and post-treatment results for subjects receiving a 16 week course of niacin.p-value: 0.025t-test, 2 sided
Primary
Hepatic Fat Content for Fenofibrate and Niacin Groups
Hepatic fat content as measured by magnetic resonance spectroscopy. A PRESS sequence was used. The results from three 10 cubic centimeter voxels positioned within the liver were averaged. The measure is a ratio of triglyceride signal to total signal.
Time frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Population: 10 (or more) subjects in each group would be sufficient for detecting changes in IHTG.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Hepatic Fat Content for Fenofibrate and Niacin Groups | Baseline | 23.2 ratio | Standard Deviation 10.2 |
| NAFLD | Hepatic Fat Content for Fenofibrate and Niacin Groups | 8 wk (fenofibrate), 16 wk (niacin) | 23.6 ratio | Standard Deviation 11.2 |
| Controls | Hepatic Fat Content for Fenofibrate and Niacin Groups | Baseline | 21.0 ratio | Standard Deviation 10.4 |
| Controls | Hepatic Fat Content for Fenofibrate and Niacin Groups | 8 wk (fenofibrate), 16 wk (niacin) | 19.7 ratio | Standard Deviation 8.9 |
Comparison: Student's t-test for paired samples was used to evaluate any difference between the two groups. The null hypothesis was that the IHTG percentage would be the same before and after treatment for subjects receiving fenofibrate.p-value: 0.301t-test, 2 sided
Comparison: A Student's t-test for paired samples was used to evaluate the effect of treatment. The null hypothesis was that the IHTG percentage for the NAFLD-niacin group at baseline and post-treatment would not change.p-value: 0.315t-test, 2 sided
Primary
Hepatic Insulin Sensitivity Index (HISI)
Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index(HISI) is the reciprocal of glucose rate of appearance \[10000/(μmol/min)\] multiplied by insulin concentration\[mU/L\]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.
Time frame: baseline cross-sectional data
Population: number of subjects determined by power calculations. Analysis was per protocol. Intrahepatic triglyceride was determined by magnetic resonance spectroscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAFLD | Hepatic Insulin Sensitivity Index (HISI) | 0.8 [10000/(μmol/min)x(mU/L)] | Standard Error 0.14 |
| Controls | Hepatic Insulin Sensitivity Index (HISI) | 1.4 [10000/(μmol/min)x(mU/L)] | Standard Error 0.26 |
Comparison: null hypothesis was no difference in hepatic insulin sensitivity between normal and high IHTG subjectsp-value: <0.019t-test, 2 sided
Primary
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
A precise measure of the ability of insulin to stimulate glucose uptake by skeletal muscle. Skeletal muscle insulin sensitivity, measured as the increase from baseline in skeletal muscle glucose uptake during insulin infusion(percentage)as part of a nine hour euglycemic hyperinsulinemic clamp study.
Time frame: baseline cross-sectional data pre and post nine hour euglycemic clamp
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAFLD | Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion. | 173 percent increase | Standard Error 13 |
| Controls | Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion. | 303 percent increase | Standard Error 23 |
Comparison: null hypothesis was no difference in skeletal muscle insulin sensitivity between groups.p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate
VLDL-apolipoprotein B (apoB) concentrations were measured as part of a VLDL metabolism study utilizing stable isotope tracers. VLDL apoB production rate, a measure of hepatic secretion of VLDL-apolipoproteinB-100 per liter of plasma per minute.
Time frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate | Baseline | 0.5 nmol/l/min | Standard Error 0.05 |
| NAFLD | Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate | 8 wk (fenofibrate), 16 wk (niacin) | 0.4 nmol/l/min | Standard Error 0.05 |
| Controls | Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate | Baseline | 0.4 nmol/l/min | Standard Error 0.04 |
| Controls | Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate | 8 wk (fenofibrate), 16 wk (niacin) | 0.4 nmol/l/min | Standard Error 0.11 |
Comparison: a Student's t-test for paired samples was used to evaluate the effect of treatment. Null hypothesis was that VLDL-apoB would be the same before and after 16 weeks on niacin in subjects with NAFLD.p-value: 0.708t-test, 2 sided
Comparison: A Student's t-test for paired samples was used to evaluate the effect of treatment. Null hypothesis was that VLDL-apoB would be the same before and after 8 weeks on fenofibrate in subjects with NAFLD.p-value: 0.022t-test, 2 sided
Secondary
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration | Baseline | 1.09 mmol/l | Standard Error 0.28 |
| NAFLD | Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration | 8 weeks (fenofibrate) or 16 weeks (niacin) | 0.50 mmol/l | Standard Error 0.1 |
| Controls | Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration | Baseline | 1.04 mmol/l | Standard Error 0.24 |
| Controls | Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration | 8 weeks (fenofibrate) or 16 weeks (niacin) | 0.64 mmol/l | Standard Error 0.23 |
Comparison: Null hypothesis was that fenofibrate would not affect VLDL-Tg concentration. We compare the pre and post-treatment results of subjects receiving an 8 week course of fenofibrate.p-value: 0.024t-test, 2 sided
Comparison: The null hypothesis was that niacin would not affect VLDL-Tg concentration. We compare the pre and post-treatment results of subjects receiving a 16 week course of niacin.p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in VLDL-Tg Clearance Rate
Very low density lipoprotein triglyceride (VLDL-Tg) clearance rate, a measure of VLDL-triglyceride removal from plasma per minute.
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Change From Baseline in VLDL-Tg Clearance Rate | Baseline | 35 (ml/min) | Standard Error 9 |
| NAFLD | Change From Baseline in VLDL-Tg Clearance Rate | 8 weeks (fenofibrate) or 16 weeks (niacin) | 56 (ml/min) | Standard Error 12 |
| Controls | Change From Baseline in VLDL-Tg Clearance Rate | Baseline | 34 (ml/min) | Standard Error 8 |
| Controls | Change From Baseline in VLDL-Tg Clearance Rate | 8 weeks (fenofibrate) or 16 weeks (niacin) | 52 (ml/min) | Standard Error 23 |
Comparison: the null hypothesis was that fenofibrate would not change the VLDL-Tg clearance ratep-value: 0.02t-test, 2 sided
Comparison: the null hypothesis was that niacin would not change the VLDL-Tg clearance ratep-value: 0.358t-test, 2 sided
Secondary
Change From Baseline in VLDL-Tg Production Rate
VLDL-TG production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute.
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NAFLD | Change From Baseline in VLDL-Tg Production Rate | Baseline | 6.4 (μmol/L/min) | Standard Error 0.7 |
| NAFLD | Change From Baseline in VLDL-Tg Production Rate | 8 weeks (fenofibrate) or 16 weeks (niacin) | 6.0 (μmol/L/min) | Standard Error 0.6 |
| Controls | Change From Baseline in VLDL-Tg Production Rate | Baseline | 7.7 (μmol/L/min) | Standard Error 1.6 |
| Controls | Change From Baseline in VLDL-Tg Production Rate | 8 weeks (fenofibrate) or 16 weeks (niacin) | 4.5 (μmol/L/min) | Standard Error 0.8 |
Comparison: Null hypothesis is that fenofibrate would not effect VLDL-Tg production rates.p-value: 0.758t-test, 2 sided
Comparison: Null hypothesis is that niacin would not effect VLDL-Tg production rates.p-value: 0.023t-test, 2 sided
Secondary
Very Low Density Lipoprotein - Triglyceride Production Rate
Very low density lipoprotein triglyceride (VLDL-TG) production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute (μmol/L/min).
Time frame: baseline cross-sectional data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAFLD | Very Low Density Lipoprotein - Triglyceride Production Rate | 6.7 μmol/L/min | Standard Error 0.5 |
| Controls | Very Low Density Lipoprotein - Triglyceride Production Rate | 3.8 μmol/L/min | Standard Error 0.3 |
Comparison: null hypothesis was that VLDL-TG production would not differ between the two groups.p-value: <0.001t-test, 2 sided