Trial Outcomes & Findings for Obesity and Nonalcoholic Fatty Liver Disease (NCT NCT00262964)
NCT ID: NCT00262964
Last Updated: 2018-07-11
Results Overview
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.
COMPLETED
NA
51 participants
baseline cross-sectional data
2018-07-11
Participant Flow
Beginning and ending recruitment dates: Beginning - 10/20/04; Ending - 09/24/07. Recruitment occurred only at Washington University in St. Louis.
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.
Participant milestones
| Measure |
NAFLD - Niacin
subjects diagnosed with NAFLD were randomized to a sixteen week regimen of niacin.
|
NAFLD - Fenofibrate
Subjects diagnosed with NAFLD were randomized to an eight week regimen of fenofibrate
|
Controls
Subjects with normal intrahepatic fat triglyceride(IHTG) levels (\<10%). IHTG was measured using magnetic resonance spectroscopy and defined as the extrapolated ratio of triglyceride signal to water signal at time t = 0.
|
NAFLD - no Drug
Subjects with elevated intrahepatic triglyceride (IHTG) levels (\>10%) who were measured only once (baseline). These subjects did not undergo drug therapy, in contrast to the NAFLD-niacin and NAFLD-fenofibrate group subjects. IHTG was measured using magnetic resonance spectroscopy and defined as the extrapolated ratio of triglyceride signal to water signal at time t = 0.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
17
|
12
|
|
Overall Study
COMPLETED
|
11
|
11
|
17
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Obesity and Nonalcoholic Fatty Liver Disease
Baseline characteristics by cohort
| Measure |
Controls
n=17 Participants
Subjects with normal intra-hepatic triglyceride content (defined by less than 10% lipid to water signal in magnetic resonance spectroscopy).
|
NAFLD
n=34 Participants
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.
|
Total
n=51 Participants
Total of all reporting groups
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|---|---|---|---|
|
Age, Customized
<=18 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Age, Customized
Between 18 and 65 years
|
17 participants
n=5 Participants
|
34 participants
n=7 Participants
|
51 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Age, Continuous
|
41 years
STANDARD_DEVIATION 3 • n=5 Participants
|
45 years
STANDARD_DEVIATION 3 • n=7 Participants
|
42 years
STANDARD_DEVIATION 3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
34 participants
n=7 Participants
|
51 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
35.11 kg/m^2
STANDARD_DEVIATION 4.33 • n=5 Participants
|
36.73 kg/m^2
STANDARD_DEVIATION 4.66 • n=7 Participants
|
36.19 kg/m^2
STANDARD_DEVIATION 4.57 • n=5 Participants
|
|
Body Weight
|
99.8 kilograms
STANDARD_DEVIATION 11.6 • n=5 Participants
|
104.1 kilograms
STANDARD_DEVIATION 15.6 • n=7 Participants
|
102.7 kilograms
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
fat as percentage of total body composition
|
42.1 percentage of total body weight
STANDARD_DEVIATION 6.9 • n=5 Participants
|
39.3 percentage of total body weight
STANDARD_DEVIATION 6.0 • n=7 Participants
|
40.3 percentage of total body weight
STANDARD_DEVIATION 6.4 • n=5 Participants
|
|
plasma glucose level
|
94.2 mg/dl
STANDARD_DEVIATION 6.0 • n=5 Participants
|
96.0 mg/dl
STANDARD_DEVIATION 8.6 • n=7 Participants
|
95.4 mg/dl
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
plasma insulin level
|
11.4 mU/L
STANDARD_DEVIATION 4.5 • n=5 Participants
|
21.2 mU/L
STANDARD_DEVIATION 9.9 • n=7 Participants
|
17.9 mU/L
STANDARD_DEVIATION 9.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline cross-sectional dataPopulation: number of subjects determined by power calculations. Analysis was per protocol. Intrahepatic triglyceride was determined by magnetic resonance spectroscopy.
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.
Outcome measures
| Measure |
NAFLD
n=34 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=17 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Hepatic Insulin Sensitivity Index (HISI)
|
0.8 [10000/(μmol/min)x(mU/L)]
Standard Error 0.14
|
1.4 [10000/(μmol/min)x(mU/L)]
Standard Error 0.26
|
PRIMARY outcome
Timeframe: baseline cross-sectional data pre and post nine hour euglycemic clampA 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.
Outcome measures
| Measure |
NAFLD
n=34 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=17 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
|
173 percent increase
Standard Error 13
|
303 percent increase
Standard Error 23
|
PRIMARY outcome
Timeframe: baseline cross-sectional data pre and post nine hour euglycemic clampThe 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.
Outcome measures
| Measure |
NAFLD
n=34 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=17 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Adipose Tissue Insulin Sensitivity
|
66 percent decrease
Standard Error 2
|
75 percent decrease
Standard Error 1
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Hepatic Fat Content for Fenofibrate and Niacin Groups
Baseline
|
23.2 ratio
Standard Deviation 10.2
|
21.0 ratio
Standard Deviation 10.4
|
|
Hepatic Fat Content for Fenofibrate and Niacin Groups
8 wk (fenofibrate), 16 wk (niacin)
|
23.6 ratio
Standard Deviation 11.2
|
19.7 ratio
Standard Deviation 8.9
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
Baseline
|
68 percent decrease
Standard Error 4
|
63 percent decrease
Standard Error 4
|
|
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
8 weeks (fenofibrate) or 16 weeks (niacin)
|
69 percent decrease
Standard Error 2
|
35 percent decrease
Standard Error 10
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Change From Baseline in Skeletal Muscle Insulin Sensitivity
Baseline
|
188 percent increase
Standard Error 36
|
183 percent increase
Standard Error 22
|
|
Change From Baseline in Skeletal Muscle Insulin Sensitivity
8 weeks (fenofibrate) or 16 weeks (niacin)
|
169 percent increase
Standard Error 28
|
142 percent increase
Standard Error 26
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Change From Baseline in Hepatic Insulin Sensitivity Index
Baseline
|
0.7 [10000/(μmol/min)x(mU/L)]
Standard Error 0.1
|
0.8 [10000/(μmol/min)x(mU/L)]
Standard Error 0.4
|
|
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
|
0.5 [10000/(μmol/min)x(mU/L)]
Standard Error 0.1
|
SECONDARY outcome
Timeframe: baseline cross-sectional dataVery 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).
Outcome measures
| Measure |
NAFLD
n=34 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=17 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Very Low Density Lipoprotein - Triglyceride Production Rate
|
6.7 μmol/L/min
Standard Error 0.5
|
3.8 μmol/L/min
Standard Error 0.3
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate
Baseline
|
0.5 nmol/l/min
Standard Error 0.05
|
0.4 nmol/l/min
Standard Error 0.04
|
|
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
|
0.4 nmol/l/min
Standard Error 0.11
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Change From Baseline in VLDL-Tg Clearance Rate
Baseline
|
35 (ml/min)
Standard Error 9
|
34 (ml/min)
Standard Error 8
|
|
Change From Baseline in VLDL-Tg Clearance Rate
8 weeks (fenofibrate) or 16 weeks (niacin)
|
56 (ml/min)
Standard Error 12
|
52 (ml/min)
Standard Error 23
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Change From Baseline in VLDL-Tg Production Rate
Baseline
|
6.4 (μmol/L/min)
Standard Error 0.7
|
7.7 (μmol/L/min)
Standard Error 1.6
|
|
Change From Baseline in VLDL-Tg Production Rate
8 weeks (fenofibrate) or 16 weeks (niacin)
|
6.0 (μmol/L/min)
Standard Error 0.6
|
4.5 (μmol/L/min)
Standard Error 0.8
|
SECONDARY outcome
Timeframe: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)
Outcome measures
| Measure |
NAFLD
n=11 Participants
subjects with intra-hepatic triglyceride content greater than 10%.
|
Controls
n=11 Participants
subjects with normal intra-hepatic triglyceride levels
|
|---|---|---|
|
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
Baseline
|
1.09 mmol/l
Standard Error 0.28
|
1.04 mmol/l
Standard Error 0.24
|
|
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
8 weeks (fenofibrate) or 16 weeks (niacin)
|
0.50 mmol/l
Standard Error 0.10
|
0.64 mmol/l
Standard Error 0.23
|
Adverse Events
NAFLD - Fenofibrate
NAFLD - Niacin
NAFLD - no Drug
Controls
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
NAFLD - Fenofibrate
n=11 participants at risk
Subjects diagnosed with NAFLD were randomized to an weight week regimen of fenofibrate
|
NAFLD - Niacin
n=11 participants at risk
subjects with intra-hepatic triglyceride signal greater than 10% placed on daily niacin for 16 weeks. The dose of medication will be gradually increased according to the protocol of most clinical trials (59): 500 mg/day during wk 1, 1000 mg/day during wk 2, 1500 mg/day during wks 3, and 2000mg/day during wks 4-16.
|
NAFLD - no Drug
n=12 participants at risk
subjects with elevated hepatic triglyceride who did not receive any drug intervention
|
Controls
n=17 participants at risk
subjects with normal hepatic triglyceride.
|
|---|---|---|---|---|
|
Hepatobiliary disorders
elevation of liver enzymes
|
9.1%
1/11 • Number of events 1 • Adverse event data was collected from baseline testing through post-treatment testing. The "NAFLD - no drug" and control groups were only followed through the baseline testing.
|
0.00%
0/11 • Adverse event data was collected from baseline testing through post-treatment testing. The "NAFLD - no drug" and control groups were only followed through the baseline testing.
|
0.00%
0/12 • Adverse event data was collected from baseline testing through post-treatment testing. The "NAFLD - no drug" and control groups were only followed through the baseline testing.
|
0.00%
0/17 • Adverse event data was collected from baseline testing through post-treatment testing. The "NAFLD - no drug" and control groups were only followed through the baseline testing.
|
Additional Information
Elisa Fabbrini, MD
Washington University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place