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NCT Number: NCT01849068

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

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.

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Key information

Conditions

Metabolic Syndrome X Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Metabolic Syndrome Nutritional and Metabolic Diseases

Age range

18 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Laval University

Québec, Quebec, G1V 0A6, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ezetimibe

Drug

Ezetimibe 10 mg/d for 12 weeks

Other names: Ezetrol

Placebo

Drug

Placebo for 12 weeks

Primary outcomes

  1. Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions

    Time frame: At the end of the two 12-week interventions (Week 12 and 24)

    We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).

    We combined the results at the end of each placebo phase from both sequence (average and standard deviation).

Secondary outcomes

  1. Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions

    Time frame: At the end of the two 12-week interventions (Week 12 and 24)

    We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).

    We combined the results at the end of each placebo phase from both sequence (average and standard deviation).

  2. Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions

    Time frame: At the end of the two 12-week interventions (Week 12 and 24)

    We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).

    We combined the results at the end of each placebo phase from both sequence (average and standard deviation).

  3. Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions

    Time frame: At the end of the two 12-week interventions (Week 12 and 24)

    We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).

    We combined the results at the end of each placebo phase from both sequence (average and standard deviation).

Sponsors and collaborators

Lead sponsor

Laval University

Other

Registry information

Acronym: EZEmRNA

Important dates

Study start
2013
Primary completion
2015
Study completion
2016
First posted
May 8, 2013
Registry last updated
Apr 12, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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