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

NCT ID: NCT01849068

Last Updated: 2016-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2016-02-29

Brief Summary

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.

Conditions

Metabolic Syndrome X

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ezetimibe

Group Type: EXPERIMENTAL

Ezetimibe

Intervention Type: DRUG

Ezetimibe 10 mg/d for 12 weeks

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for 12 weeks

Interventions

Ezetimibe

Ezetimibe 10 mg/d for 12 weeks

Intervention Type: DRUG

Placebo

Placebo for 12 weeks

Intervention Type: DRUG

Other Intervention Names

Ezetrol

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Laval University

OTHER

Sponsor Role: lead

Responsible Party

Patrick Couture

MD, FRCP, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Couture, MD, FRCP, PhD

Role: PRINCIPAL_INVESTIGATOR

Laval University

Locations

Laval University

Québec, Quebec, Canada

Countries

Canada

Other Identifiers

INAF-B13-04-1195

Identifier Type: -

Identifier Source: org_study_id