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Insulin Resistance in Non-alcoholic Fatty Liver Disease

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ClinicalTrials.gov Identifier: NCT00252499
Recruitment Status : Terminated (Protocol drug change required new clinicaltrails.gov entry)
First Posted : November 11, 2005
Results First Posted : April 11, 2014
Last Update Posted : August 20, 2014
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Basic Science
Conditions Fatty Liver
Insulin Resistance
Interventions Drug: rosiglitazone
Drug: fenofibrate
Drug: placebo for rosiglitazone
Drug: placebo for fenofibrate
Enrollment 13
Recruitment Details Subjects were recruited between 2006 and 2011 through referral from local gastroenterologists.
Pre-assignment Details Subjects underwent a screening visit prior to randomization to ensure that they qualified for the study.
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Period Title: Overall Study
Started 5 2 6
Completed 4 2 6
Not Completed 1 0 0
Reason Not Completed
Lost to Follow-up             1             0             0
Arm/Group Title Arm 1 Arm 2 Arm 3 Total
Hide Arm/Group Description matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid Total of all reporting groups
Overall Number of Baseline Participants 5 2 6 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 2 participants 6 participants 13 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
 100.0%
2
 100.0%
6
 100.0%
13
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 2 participants 6 participants 13 participants
49.2  (7.3) 56.5  (4.95) 54.17  (5.08) 52.6  (6.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 2 participants 6 participants 13 participants
Female
2
  40.0%
1
  50.0%
2
  33.3%
5
  38.5%
Male
3
  60.0%
1
  50.0%
4
  66.7%
8
  61.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants 2 participants 6 participants 13 participants
5 2 6 13
1.Primary Outcome
Title Liver/Spleen Ratio at 6 Months
Hide Description Liver fat was estimated by non-contrast CT scan measuring the density ratio between the liver and spleen by Hounsfield units (liver/spleen ratio), which has been previously correlated with liver fat quantification by magnetic resonance spectroscopy.Ten separate measurements equally distributed throughout the liver and spleen were obtained and the Hounsfield units averaged. In subjects with more than one slice through the liver and spleen, the values for all slices were averaged.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description:
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Number of Participants Analyzed 4 2 6
Mean (Standard Error)
Unit of Measure: ratio
0.85  (0.08) 0.96  (0.25) 0.60  (0.17)
2.Secondary Outcome
Title Change in Alanine Aminotransferase (ALT) Levels From Baseline to 6 Months
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description:
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Number of Participants Analyzed 4 2 6
Mean (Standard Error)
Unit of Measure: U/L
-11.5  (12.9) -35.0  (37.0) -15.2  (4.5)
3.Secondary Outcome
Title Change in the Liver Spleen Ratio by CT Scan From Baseline to 6 Months as a Measure of Fat in the Liver
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description:
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Number of Participants Analyzed 4 2 6
Mean (Standard Error)
Unit of Measure: ratio
.09  (.10) .34  (.09) -.16  (.10)
4.Secondary Outcome
Title Change in Peripheral Insulin Sensitivity From Baseline to 6 Months
Hide Description A two-step stable isotope labeled, hyperinsulinemic-euglycemic clamp procedure was performed with a low dose insulin infusion (20 mU/m2/min) for 3 hours followed by a primed high dose insulin infusion (160 mU/m2/min x 5 minutes then 80 mU/m2/min) for two hours. D20 was infused and adjusted to maintain the blood glucose at 90 mg/dl. Samples for glucose, insulin and 6,6 2d glucose were drawn every 15 minutes during the final half hour of the basal, low dose and high dose insulin periods. Whole body insulin sensitivity was calculated as the rate of glucose disposal (Rd)/lean body mass during the high dose insulin infusion.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
One person in Arm 1 dropped out and thus is lacking 6 month data. The 6 month isotope data to calculate the rate of glucose disposal was not available for one subject in Arm 3.
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description:
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Number of Participants Analyzed 4 2 5
Mean (Standard Error)
Unit of Measure: mg/min/kg
1.65  (2.11) 0.123  (2.62) -0.24  (1.14)
5.Secondary Outcome
Title Changes in Intra-abdominal Fat Area From Baseline to 6 Months
Hide Description Unenhanced CT scan images were obtained on a General Electric Discovery HD750 CT scanner. Intra-abdominal (IAF) areas were measured at the top of the iliac crest and quantified using the Tomovision program (SliceOMatic V4.3) by one trained technologist.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description:
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Number of Participants Analyzed 5 2 6
Mean (Standard Error)
Unit of Measure: mm2
885  (874) 440  (2788) 108  (3416)
6.Secondary Outcome
Title Change in Hepatic Insulin Sensitivity From Baseline to 6 Months
Hide Description Hepatic insulin sensitivity was determined as the percent suppression of endogenous glucose production (EGP) at the end of the low dose insulin clamp.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description:
matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Number of Participants Analyzed 4 2 5
Mean (Standard Error)
Unit of Measure: percent of baseline EGP
23.3  (7.8) -4.09  (4.34) 4.91  (9.32)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm 1 Arm 2 Arm 3
Hide Arm/Group Description matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
All-Cause Mortality
Arm 1 Arm 2 Arm 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm 1 Arm 2 Arm 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/2 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm 1 Arm 2 Arm 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/5 (60.00%)      0/2 (0.00%)      4/6 (66.67%)    
Blood and lymphatic system disorders       
leg edema *  0/5 (0.00%)  0 0/2 (0.00%)  0 2/6 (33.33%)  2
General disorders       
vasovagal reaction *  2/5 (40.00%)  2 0/2 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders       
gout attack *  1/5 (20.00%)  1 0/2 (0.00%)  0 2/6 (33.33%)  3
Renal and urinary disorders       
increased serum Creatinine *  0/5 (0.00%)  0 0/2 (0.00%)  0 2/6 (33.33%)  2
*
Indicates events were collected by non-systematic assessment
Due to recruitment difficulties and concerns about the safety of thiazolidinediones, recruitment was stopped without achieving adequate sample size (16/arm). Thus, no definitive conclusions can be made about the study medications.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Kristina Utzschneider, MD
Organization: VA Puget Sound Health Care System
Phone: 206-277-3568
Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
ClinicalTrials.gov Identifier: NCT00252499     History of Changes
Other Study ID Numbers: CDA-2-044-08S
First Submitted: November 9, 2005
First Posted: November 11, 2005
Results First Submitted: November 12, 2013
Results First Posted: April 11, 2014
Last Update Posted: August 20, 2014