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Trial record 9 of 37 for:    Niemann Pick C

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Patrick Couture, Laval University
ClinicalTrials.gov Identifier:
NCT01849068
First received: May 6, 2013
Last updated: March 14, 2016
Last verified: March 2016
  Purpose

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.


Condition Intervention Phase
Metabolic Syndrome X
Drug: Ezetimibe
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

    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).



Enrollment: 20
Study Start Date: June 2013
Study Completion Date: February 2016
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ezetimibe Drug: Ezetimibe
Ezetimibe 10 mg/d for 12 weeks
Other Name: Ezetrol
Placebo Comparator: Placebo Drug: Placebo
Placebo for 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849068

Locations
Canada
Laval University
Quebec, Canada, G1V 0A6
Sponsors and Collaborators
Laval University
Investigators
Principal Investigator: Patrick Couture, MD, FRCP, PhD Laval University
  More Information

Responsible Party: Patrick Couture, MD, FRCP, PhD, Laval University
ClinicalTrials.gov Identifier: NCT01849068     History of Changes
Other Study ID Numbers: INAF-B13-04-1195 
Study First Received: May 6, 2013
Results First Received: February 15, 2016
Last Updated: March 14, 2016
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on September 23, 2016