Clinical trial NCT00632840: Pharmacological Regulation of Fat Transport in Metabolic Syndrome
Official title: Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate With the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Lipid Disorders
Hypertriglyceridemia
Cardiovascular Disease
Lead sponsor: The University of Western Australia
Sponsor class: OTHER
Collaborators: name: National Heart Foundation, Australia
First posted: 2008-03-11
Enrollment: 11
Sex: MALE
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether atorvastatin and fenofibrate are effective in the treatment of lipid disorders in obese, insulin resistant subjects.

Detailed description: Insulin resistance is a heterogeneous metabolic disorder of complex etiology. It underpins dyslipoproteinemia, a key feature of the metabolic syndrome (MetS) that independently predicts cardiovascular disease (CVD). Hypertriglyceridemia, the most consistent lipid disorder in subjects with obesity and type 2 diabetes mellitus, is chiefly a consequence of overproduction and delayed clearance of triglyceride-rich lipoproteins (TRLs). Although the precise mechanisms involved are incompletely understood, experimental and clinical evidence suggests that elevated apolipoprotein (apo) C-III may play a crucial role in the dysregulation of TRL metabolism. investigating the effects of these agents on VLDL-apoC-III kinetics. In this study, we aimed to examine the effect of two lipid-regulating agents, atorvastatin and fenofibrate on VLDL-apoC-III transport. We hypothesized that atorvastatin and fenofibrate would have similar effects on apoC-III transport by decreasing the production and increasing the catabolism of VLDL-apoC-III.

Eligibility criteria: Inclusion Criteria:

any three of the followings

* waist circumference \>102cm
* triglycerides \>1.7 mmol/L
* HDL-cholesterol \<1.05 mmol/L
* blood glucose \>6.1 mmol/L
* blood pressure \>130/85mmHg

Exclusion Criteria:

* plasma cholesterol \>7mmo/L
* triglycerides \>4.5mmo/L
* diabetes mellitus (defined by oral glucose tolerance test)
* CVD
* consumption of \>30g alcohol/day
* use of agents affecting lipid metabolism
* APOE2/E2 genotype, macroproteinuria
* creatinaemia (\>120umol/L)
* hypothyroidism
* abnormal liver and muscle enzymes.

Primary outcomes:
measure: VLDL-apoC-III transport rate
timeFrame: 5 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: The University of Western Australia
name: Dick C Chan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chan DC, Watts GF, Ooi EM, Rye KA, Ji J, Johnson AG, Barrett PH. Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome. Diabetes Care. 2009 Nov;32(11):2111-3. doi: 10.2337/dc09-0519. Epub 2009 Aug 3.
citation: Chan DC, Barrett PH, Ooi EM, Ji J, Chan DT, Watts GF. Very low density lipoprotein metabolism and plasma adiponectin as predictors of high-density lipoprotein apolipoprotein A-I kinetics in obese and nonobese men. J Clin Endocrinol Metab. 2009 Mar;94(3):989-97. doi: 10.1210/jc.2008-1457. Epub 2008 Dec 30.