Clinical trial NCT00392717: Regulation of Lipoprotein Metabolism in Obese Men
Official title: Effect of Atorvastatin and Fish Oils on Lipoprotein Metabolism in Visceral Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Dyslipidemia
Insulin Resistance
Keywords: lipoprotein metabolism
cardiovascular disease
obesity
Lead sponsor: The University of Western Australia
Sponsor class: OTHER
First posted: 2006-10-26
Enrollment: 48
Sex: MALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Visceral obesity is strongly associated with dyslipidaemia (hypertriglyceridaemia, low HDL-cholesterol and mildly elevated LDL-cholesterol) and insulin resistance, key characteristics of metabolic syndrome (MetS). Recent evidence has clearly established that the risk of CVD is increased in subjects with the MetS. The precise reason for this remains unclear, but appears to be closely related with dyslipidaemia. Effective management of dyslipidaemia is important to reduce the risk of CVD in these subjects.

Hypothesis: Inhibition of hepatic cholesterol synthesis by statins and triglyceride synthesis by fish oils improve lipoprotein metabolism in visceral obese men.

Detailed description: The study employed a factorial study design, stable isotopy and mathematical modelling to examine the independent and combined effects of decreasing cholesterol substrate availability with atorvastatin and decreasing triglyceride substrate availability with fish oils on lipoprotien kinetics (apoB, apoA, apoC-III and chylomicron remnants) in insulin-resistant men with visceral obesity.

Eligibility criteria: Inclusion Criteria:

* Obesity was defined as a waist circumference \>100 cm, waist:hip ratio \>0.97 and BMI \>29 kg/m2.
* Subjects were selected for having insulin-resistance, defined as a homostasis model assessment (HOMA) score (21) \>5.1 (i.e. one SD above the mean for a reference population of 22 lean, normolipidemic healthy males of similar age).
* All subjects had plasma triglyceride \>1.2 mmol/L and cholesterol \>5.2 mmol/L at screening while consuming ad libitum, weight-maintaining diets

Exclusion Criteria:

* diabetes mellitus, apolipoprotein E2/E2 genotype, macroproteinuria, creatinemia, hypothyrodism, or abnormal liver enzymes.
* Subjects did not consume fish oil supplements or drank more than 30g alcohol/day.
* None reported a history of CVD, or was taking medication or other agents known to affect lipid metabolism.

Primary outcomes:
measure: Fractional catabolic rate of apoB, apoA, apoC-III and chylomicron remnants (before and after 6 week treatments)
measure: Production rate of apoB, apoA, apoC-III and chylomicron remnants (before and after 6 week treatments)
Secondary outcomes:
measure: Cholesterol
measure: Triglyceride
measure: LDL-cholesterol
measure: Adipocytokines
measure: Genetic polymorphisms
Other outcomes:
Locations:
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: The University of Western Australia
name: Dick C Chan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Western Australia
name: Gerald F Watts, MBBS PhD
role: STUDY_CHAIR
affiliation: The University of Western Australia
name: P Hugh H Barrett, PhD
role: STUDY_DIRECTOR
References:
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.