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

Metabolic Syndrome X Clinical Trial

— EZEmRNA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01849068
• Other study ID #: INAF-B13-04-1195
• Status: Recruiting
• Phase: Phase 3
• First received: May 6, 2013
• Last updated: August 24, 2015
• Start date: June 2013
• Est. completion date: December 2015

Study information

• Verified date: August 2015
• Source: Laval University
• Contact: Patrick Couture, MD, PhD, FRCP
• Phone: 418-654-2106
• Email: patrick.couture[@]crchul.ulaval.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance
• Metabolic Syndrome X

Intervention

Drug:
• Ezetimibe
Ezetimibe 10 mg/d for 12 weeks
• Placebo
Placebo for 12 weeks

Locations

Country	Name	City	State
Canada	Laval University	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Laval University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in intestinal mRNA expression levels of LDL receptor between the two 12-week interventions		At the end of the two 12-week interventions (Week 12 and 24)	No
Secondary	Change in intestinal protein mass levels of LDL receptor between the two 12-week interventions		At the end of the two 12-week interventions (Week 12 and 24)	No
Secondary	Change in intestinal mRNA expression levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase between the two 12-week interventions		At the end of the two 12-week interventions (Week 12 and 24)	No
Secondary	Change in intestinal protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase between the two 12-week interventions		At the end of the two 12-week interventions (Week 12 and 24)	No