Trial Outcomes & Findings for Insulin Resistance in Non-alcoholic Fatty Liver Disease (NCT NCT00252499)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

13 participants

Primary outcome timeframe

6 months

Results posted on

2014-08-20

Participant Flow

Subjects were recruited between 2006 and 2011 through referral from local gastroenterologists.

Subjects underwent a screening visit prior to randomization to ensure that they qualified for the study.

Participant milestones

Participant milestones
Measure	Arm 1 matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Study STARTED	5	2	6
Overall Study COMPLETED	4	2	6
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Overall Study Lost to Follow-up	1	0	0

Baseline Characteristics

Insulin Resistance in Non-alcoholic Fatty Liver Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 n=5 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=6 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	13 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	49.2 years STANDARD_DEVIATION 7.3 • n=5 Participants	56.5 years STANDARD_DEVIATION 4.95 • n=7 Participants	54.17 years STANDARD_DEVIATION 5.08 • n=5 Participants	52.6 years STANDARD_DEVIATION 6.27 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment United States	5 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants	13 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months

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.

Outcome measures

Outcome measures
Measure	Arm 1 n=4 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=6 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Liver/Spleen Ratio at 6 Months	0.85 ratio Standard Error 0.08	0.96 ratio Standard Error 0.25	0.60 ratio Standard Error 0.17

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Arm 1 n=4 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=6 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Change in Alanine Aminotransferase (ALT) Levels From Baseline to 6 Months	-11.5 U/L Standard Error 12.9	-35.0 U/L Standard Error 37.0	-15.2 U/L Standard Error 4.5

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Arm 1 n=4 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=6 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Change in the Liver Spleen Ratio by CT Scan From Baseline to 6 Months as a Measure of Fat in the Liver	.09 ratio Standard Error .10	.34 ratio Standard Error .09	-.16 ratio Standard Error .10

SECONDARY outcome

Timeframe: 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm 1 n=4 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=5 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Change in Peripheral Insulin Sensitivity From Baseline to 6 Months	1.65 mg/min/kg Standard Error 2.11	0.123 mg/min/kg Standard Error 2.62	-0.24 mg/min/kg Standard Error 1.14

SECONDARY outcome

Timeframe: 6 months

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.

Outcome measures

Outcome measures
Measure	Arm 1 n=5 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=6 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Changes in Intra-abdominal Fat Area From Baseline to 6 Months	885 mm2 Standard Error 874	440 mm2 Standard Error 2788	108 mm2 Standard Error 3416

SECONDARY outcome

Timeframe: 6 months

Hepatic insulin sensitivity was determined as the percent suppression of endogenous glucose production (EGP) at the end of the low dose insulin clamp.

Outcome measures

Outcome measures
Measure	Arm 1 n=4 Participants matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 Participants rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=5 Participants micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Change in Hepatic Insulin Sensitivity From Baseline to 6 Months	23.3 percent of baseline EGP Standard Error 7.8	-4.09 percent of baseline EGP Standard Error 4.34	4.91 percent of baseline EGP Standard Error 9.32

Adverse Events

Arm 1

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Arm 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm 3

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm 1 n=5 participants at risk matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd	Arm 2 n=2 participants at risk rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd	Arm 3 n=6 participants at risk micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Musculoskeletal and connective tissue disorders gout attack	20.0% 1/5 • Number of events 1	0.00% 0/2	33.3% 2/6 • Number of events 3
General disorders vasovagal reaction	40.0% 2/5 • Number of events 2	0.00% 0/2	0.00% 0/6
Blood and lymphatic system disorders leg edema	0.00% 0/5	0.00% 0/2	33.3% 2/6 • Number of events 2
Renal and urinary disorders increased serum Creatinine	0.00% 0/5	0.00% 0/2	33.3% 2/6 • Number of events 2

Additional Information

Kristina Utzschneider, MD

VA Puget Sound Health Care System

Phone: 206-277-3568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place