Clinical trial NCT00240305: A Study to Investigate the Effect of Rosuvastatin (CRESTOR®) on High Density Lipoprotein Kinetics in Patients With the Metabolic Syndrome
Official title: A Randomised, Double-Blind, Placebo Controlled, Crossover Dose-Ranging Study to Investigate the Effect of Rosuvastatin (CRESTOR®) on High Density Lipoprotein Kinetics in Patients With the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metabolic Syndrome
Dyslipidemia
Keywords: Metabolic Syndrome
Dyslipidaemia
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-10-18
Enrollment: 15
Sex: MALE
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the dose-related effect of treatment with rosuvastatin on production and fractional catabolism of apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), and on the plasma apoA-I, apoA-II and high-density lipoprotein cholesterol (HDL-C) concentration.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* male aged 30 to 70 years of age
* LDL-C \<6 mmol/L
* HDL-C ≤1.2 mmol/L
* at least 2 of the following:
* insulin resistance (fasting glucose \>6 mmol/L or insulin \>10 mU/L or HOMA score \>2.5)
* central obesity (waist circumference \>=94 cm).
* plasma triglycerides \>=1.7 and \<4.5 mmol/L.
* blood pressure \>=130/ \>=85 mm Hg or on drug treatment for hypertension

Exclusion Criteria:

* LDL cholesterol \>=6 mmol/L
* pre-existing or history of cardiovascular disease, diabetes, renal dysfunction, anaemia, history of significant dyspepsia or gastrointestinal disease
* apolipoprotein genotype E2/E2

Primary outcomes:
measure: Determine the dose-related effect of treatment with rosuvastatin on production & fractional catabolism of apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), & on the plasma apoA-I, apoA-II & high-density lipoprotein cholesterol (HDL-C) c
Secondary outcomes:
measure: Determine the dose-related effect of treatment with rosuvastatin on cellular cholesterol efflux,total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-LDL-C, triglyceride & pre1-HDL concentrations,HDL2,HDL3 cholesterol ratio
measure: Cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activity
measure: Lathosterol and campesterol, total apolipoprotein B (apoB), nonesterified fatty acids (NEFA) and apolipoprotein C-III (apoC-III) plasma concentrations.
Other outcomes:
Locations:
city: Perth
country: Australia
facility: Research Site
state: Western Australia
Study officials:
affiliation: University Department of Medicine, Royal Perth Hospital, University of Western Australia
name: Gerald F. Watts, BSc PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ng TW, Ooi EM, Watts GF, Chan DC, Meikle PJ, Barrett PH. Association of Plasma Ceramides and Sphingomyelin With VLDL apoB-100 Fractional Catabolic Rate Before and After Rosuvastatin Treatment. J Clin Endocrinol Metab. 2015 Jun;100(6):2497-501. doi: 10.1210/jc.2014-4348. Epub 2015 Mar 27.
citation: Ng TW, Ooi EM, Watts GF, Chan DC, Weir JM, Meikle PJ, Barrett PH. Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. J Clin Endocrinol Metab. 2014 Nov;99(11):E2335-40. doi: 10.1210/jc.2014-1665. Epub 2014 Aug 20.
citation: Ooi EM, Watts GF, Chan DC, Chen MM, Nestel PJ, Sviridov D, Barrett PH. Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome. Diabetes Care. 2008 Aug;31(8):1656-61. doi: 10.2337/dc08-0358. Epub 2008 May 28.
citation: Ooi EM, Barrett PH, Chan DC, Nestel PJ, Watts GF. Dose-dependent effect of rosuvastatin on apolipoprotein B-100 kinetics in the metabolic syndrome. Atherosclerosis. 2008 Mar;197(1):139-46. doi: 10.1016/j.atherosclerosis.2007.03.004. Epub 2007 Apr 9.