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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:
Sponsor: Laval University

Current Primary Outcome: 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) ]

Original Primary Outcome: 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) ]

Current Secondary Outcome:

• 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).

• 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).

• 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).

Original Secondary Outcome:

• Change in intestinal protein mass 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) ]
• 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) ]
• Change in intestinal protein mass 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) ]

Information By: Laval University

Dates:
Date Received: May 6, 2013
Date Started: June 2013
Date Completion:
Last Updated: March 14, 2016
Last Verified: March 2016