Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study (EZEmRNA)

Laval University

Status and phase

Completed

Phase 3

Conditions

Metabolic Syndrome X

Treatments

Drug: Ezetimibe

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT01849068

INAF-B13-04-1195

Details and patient eligibility

About

Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. The impact of a treatment with ezetimibe on intestinal gene expression and protein mass levels of LDL receptor and other key genes involved in intestinal cholesterol homeostasis will be examined in dyslipidemic men with insulin-resistance. In the present study, gene expression studies and protein mass levels will be assessed on duodenal biopsies by real-time polymerase chain reaction (rt-PCR) and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. The primary objective of this proposal is to examine the effects of ezetimibe on intestinal gene expression (rt-PCR) and protein mass levels (LC-MS/MS) of LDL receptor in dyslipidemic men with insulin-resistance. The secondary objective is to examine the impact of ezetimibe treatment on intestinal gene expression and protein mass levels of sterol regulatory element-binding protein (SREBP)-2, Niemann-Pick C1-Like1 (NPC1L1), ATP binding cassette gene (ABCG)-5/8, proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase.

Primary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of LDL receptor in dyslipidemic men with insulin-resistance.

Secondary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase in dyslipidemic men with insulin-resistance.

Enrollment

20 patients

Sex

Male

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Men aged between 18-60 years
Waist circumference > 102 cm
HDL-cholesterol < 1.1 mmol/L
Triglycerides > 1.7 mmol/L
Fasting blood glucose > 6.1 mmol/L
Normal blood pressure (<130/85)

Exclusion criteria

Women
Men < 18 or > 60 years
Smokers (> 1 cigarette/day)
Body weight variation > 10% during the last 6 months prior to the study baseline
Subjects with a previous history of cardiovascular disease
Subjects with type 2 diabetes
Subjects with a monogenic dyslipidemia
Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
Subjects with endocrine or gastrointestinal disorders
History of alcohol or drug abuse within the past 2 years
Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.