Trial Outcomes & Findings for Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation (NCT NCT00470262)

NCT ID: NCT00470262

Last Updated: 2016-07-21

Results Overview

Insulin sensitivity was measure through frequently sampled intravenous glucose tolerance test. Subjects presented to research center fasting. Blood samples were collected at -21, -11, and -1 minutes. At time t=0 initiates the start of the IVGTT and the injection of glucose into the non-sampling arm. The glucose dose was calculated as 11.4g/m2 of body surface area, given as a 50% dextrose solution. This glucose injection was administered over 60 seconds or less. At time t=20 minutes, an insulin dose of 0.04u/kg was administered over 30 seconds. Blood samples were collected at times t=2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 70, 90, 100, 120, 140, 160, and 180. If blood sugar did not return to a steady state the test was continued to t= 210 or t= 240.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 27 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2016-07-21

Participant Flow

Participant milestones

Measure	Fenofibrate Treatment with fenofibrate 145mg PO QD	Piolitazone 45 mg PO QD + Fenofibrate 145mg PO QD Pioglitazone and Fenofibrate: Subjects will be randomized to a combination of both fenofibrate(145mg PO QD) and pioglitazone 45 mg PO QD
Overall Study STARTED	15	12
Overall Study COMPLETED	13	12
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Fenofibrate Treatment with fenofibrate 145mg PO QD	Piolitazone 45 mg PO QD + Fenofibrate 145mg PO QD Pioglitazone and Fenofibrate: Subjects will be randomized to a combination of both fenofibrate(145mg PO QD) and pioglitazone 45 mg PO QD
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation

Baseline characteristics by cohort

Measure	Fenofibrate 145 mg PO QD n=15 Participants Treatment fenofibrate 145 mg PO QD in subjects with pre diabetes	Fenofibrate 145 mg PO QD and Pioglitazone 45mg PO QD n=12 Participants Treatment with Fenofibrate 145 mg PO QD and Pioglitazone 45mg PO QD in subjects with pre diabetes	Total n=27 Participants Total of all reporting groups
Age, Continuous	48.69 years STANDARD_DEVIATION 8.46 • n=5 Participants	44.67 years STANDARD_DEVIATION 11.49 • n=7 Participants	46.76 years STANDARD_DEVIATION 10.03 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	12 participants n=7 Participants	27 participants n=5 Participants
BMI	34.06 kg/m^2 STANDARD_DEVIATION 3.51 • n=5 Participants	33.93 kg/m^2 STANDARD_DEVIATION 3.49 • n=7 Participants	33.99 kg/m^2 STANDARD_DEVIATION 3.43 • n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Insulin sensitivity was measure through frequently sampled intravenous glucose tolerance test. Subjects presented to research center fasting. Blood samples were collected at -21, -11, and -1 minutes. At time t=0 initiates the start of the IVGTT and the injection of glucose into the non-sampling arm. The glucose dose was calculated as 11.4g/m2 of body surface area, given as a 50% dextrose solution. This glucose injection was administered over 60 seconds or less. At time t=20 minutes, an insulin dose of 0.04u/kg was administered over 30 seconds. Blood samples were collected at times t=2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 70, 90, 100, 120, 140, 160, and 180. If blood sugar did not return to a steady state the test was continued to t= 210 or t= 240.

Outcome measures

Measure	Fenofibrate 145mg PO QD n=13 Participants Treatment with fenofibrate in subjects with pre diabetes	Fenofibrate 145 mg PO QD + Pioglitazone n=12 Participants Treatment with fenofibrate and pioglitazone in subjects with pre diabetes
Insulin Sensitivity post	1.89 mg*kg^-1*min^-1 Standard Deviation 0.88	2.93 mg*kg^-1*min^-1 Standard Deviation 1.3
Insulin Sensitivity pre	1.48 mg*kg^-1*min^-1 Standard Deviation 0.64	1.73 mg*kg^-1*min^-1 Standard Deviation 0.75

SECONDARY outcome

Timeframe: 3 months

Intramyocellular lipid was measured using immunohistochemistry (using oil Red O staining) in muscle biopsy specimens. Oil red O-stained muscle sections were magnified with an Olympus Provis (Tokyo, Japan) light microscope, and images were digitally captured by using a connected charge-coupled device camera (Sony, Tokyo, Japan). Fiber-typed and oil red O-stained fibers were matched. The oil red O staining intensity of either type 1 or 2 muscle fibers was quantified using National Institutes of Health Image program (http://rsb.info.nih.gov/nih-image/). By adjusting a density threshold, the software was set to recognize the presence of one fat droplet only if its highlighted surface was exceeding 0.40 μm2 or larger. Muscle lipid content was calculated by total area of lipid droplets in a given muscle fiber divided by the total area of the same fiber. The mean number of fibers analyzed per sample was 40 for type 1 and 2 muscle fibers

Outcome measures

Measure	Fenofibrate 145mg PO QD n=13 Participants Treatment with fenofibrate in subjects with pre diabetes	Fenofibrate 145 mg PO QD + Pioglitazone n=12 Participants Treatment with fenofibrate and pioglitazone in subjects with pre diabetes
IMCL pre	3.67 % of lipid area stained Standard Deviation 1.30	5.32 % of lipid area stained Standard Deviation 0.65
IMCL post	3.46 % of lipid area stained Standard Deviation 2.36	2.82 % of lipid area stained Standard Deviation 0.56

Adverse Events

Fenofibrate 145mg PO QD

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Fenofibrate 145mg PO QD n=15 participants at risk Treatment with fenofibrate 145 mg PO QD in subjects with pre diabetes	Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD n=12 participants at risk Treatment with fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD in subjects with pre diabetes
Nervous system disorders Syncope	0.00% 0/15	8.3% 1/12 • Number of events 1

Additional Information

Dr. Neda Rasouli

Denver VA Medical Center

Phone: 303-399-8020

Email: neda.rasouli@ucdenver.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place