Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Ezetimibe
干预措施: Ezetimibe (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions
时间窗: 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).
次要结局
- 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))
- Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions(At the end of the two 12-week interventions (Week 12 and 24))
- Change in Protein 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))
研究者
Patrick Couture
MD, FRCP, PhD
Laval University