Obesity and Nonalcoholic Fatty Liver Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00262964
First received: December 6, 2005
Last updated: July 2, 2010
Last verified: July 2010
Results First Received: March 15, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Single Blind (Subject);   Primary Purpose: Treatment
Condition: Non-Alcoholic Fatty Liver Disease
Interventions: Drug: Niacin
Drug: fenofibrate
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    NAFLD - Niacin     NAFLD - Fenofibrate     Controls     NAFLD - no Drug  
STARTED     11     11     17     12  
COMPLETED     11     11     17     12  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Controls Subjects with normal intra-hepatic triglyceride content (defined by less than 10% lipid to water signal in magnetic resonance spectroscopy).
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.
Total Total of all reporting groups

Baseline Measures
    Controls     NAFLD     Total  
Number of Participants  
[units: participants]
  17     34     51  
Age, Customized  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     17     34     51  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  41  ± 3     45  ± 3     42  ± 3  
Gender  
[units: participants]
     
Female     13     24     37  
Male     4     10     14  
Region of Enrollment  
[units: participants]
     
United States     17     34     51  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  35.11  ± 4.33     36.73  ± 4.66     36.19  ± 4.57  
Body Weight  
[units: kilograms]
Mean ± Standard Deviation
  99.8  ± 11.6     104.1  ± 15.6     102.7  ± 14.4  
fat as percentage of total body composition [1]
[units: percentage of total body weight]
Mean ± Standard Deviation
  42.1  ± 6.9     39.3  ± 6.0     40.3  ± 6.4  
plasma glucose level [2]
[units: mg/dl]
Mean ± Standard Deviation
  94.2  ± 6.0     96.0  ± 8.6     95.4  ± 7.8  
plasma insulin level [3]
[units: mU/L]
Mean ± Standard Deviation
  11.4  ± 4.5     21.2  ± 9.9     17.9  ± 9.6  
[1] fat as percentage of total body composition as characterized using whole body Dual Energy X-ray Absorptiometry (DEXA).
[2] fasting plasma glucose level
[3] fasting plasma insulin



  Outcome Measures
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1.  Primary:   Hepatic Insulin Sensitivity Index (HISI)   [ Time Frame: baseline cross-sectional data ]

2.  Primary:   Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.   [ Time Frame: baseline cross-sectional data pre and post nine hour euglycemic clamp ]

3.  Primary:   Adipose Tissue Insulin Sensitivity   [ Time Frame: baseline cross-sectional data pre and post nine hour euglycemic clamp ]

4.  Primary:   Hepatic Fat Content for Fenofibrate and Niacin Groups   [ Time Frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin) ]

5.  Primary:   Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups   [ Time Frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin) ]

6.  Primary:   Change From Baseline in Skeletal Muscle Insulin Sensitivity   [ Time Frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) ]

7.  Primary:   Change From Baseline in Hepatic Insulin Sensitivity Index   [ Time Frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) ]

8.  Secondary:   Very Low Density Lipoprotein - Triglyceride Production Rate   [ Time Frame: baseline cross-sectional data ]

9.  Secondary:   Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate   [ Time Frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin) ]

10.  Secondary:   Change From Baseline in VLDL-Tg Clearance Rate   [ Time Frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) ]

11.  Secondary:   Change From Baseline in VLDL-Tg Production Rate   [ Time Frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) ]

12.  Secondary:   Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration   [ Time Frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Elisa Fabbrini, MD
Organization: Washington University School of Medicine
phone: 314-362-8156
e-mail: efabbrini@dom.wustl.edu


No publications provided


Responsible Party: Samuel Klein, MD, William H. Danforth Professor of Medicine and Nutritional Science, Washington University
ClinicalTrials.gov Identifier: NCT00262964     History of Changes
Other Study ID Numbers: DK37948, R01DK037948
Study First Received: December 6, 2005
Results First Received: March 15, 2010
Last Updated: July 2, 2010
Health Authority: United States: Federal Government