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Trial record 101 of 813 for:    APOB

Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia (LA-PBMC)

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ClinicalTrials.gov Identifier: NCT02462655
Recruitment Status : Completed
First Posted : June 4, 2015
Last Update Posted : March 8, 2016
Sponsor:
Information provided by (Responsible Party):
Patrick Couture, Laval University

Brief Summary:

Familial hypercholesterolemia (FH) is an autosomal codominant single-gene disorder caused by mutations in the LDL receptor gene that disrupt the normal clearance of LDL particles from the plasma compartment. Heterozygous patients present a 2- to 3-fold raise in plasma LDL-cholesterol (C) concentrations, tendinous xanthomatosis and premature atherosclerotic coronary heart disease (CHD), usually occurring between the age of 35 and 55 years. Since the mid-1970s, LDL-C has been removed from the blood of patients using plasmapheresis, and this technique has been shown to improve the life expectancy of FH homozygotes. LDL apheresis selectively removes LDL particles but not immunoglobulins and other beneficial proteins, thereby overcoming a potential drawback of the traditional plasmapheresis method. LDL-C is effectively reduced by more than 60% immediately after LDL apheresis, although LDL levels rebound rapidly.

Dextran sulfate adsorption is a commonly apheresis technique used in familial hypercholesterolemia patients. In this apheresis plasma is separated from red blood cells and passed over columns of cellulose beads containing dextran sulfate which binds apolipoprotein B (apoB) by a highly selective electrostatic binding mechanism. Since LDL, very-low density lipoprotein (VLDL), and Lipoprotein (a) all contain apoB, dextran sulfate adsorption apheresis selectively reduces these lipoproteins while having little effect on the non-apoB containing HDL particles. In clinical practice, LDL apheresis reduces the rate of future cardiovascular events and has been postulated to have additional effects on potentially pro-atherogenic factors. Some proteins have been identified with adhesive characteristics to lipoproteins, rheological, immunological and inflammation relevant proteins16-19 that influence microcirculation as well as the inflammatory response. However, no studies have yet to investigate the impact of LDL apheresis on the expression of different genes involved in cardiovascular disease.

The main objective of the present research project is to investigate the impact of the LDL apheresis dextran sulfate adsorption system on the messenger ribonucleic acid (mRNA) expression of genes involved in cardiovascular disease using microarrays analysis in 9 FH homozygotes.


Condition or disease Intervention/treatment Phase
Familial Hypercholesterolemia Other: Pre-lipid apheresis Other: Post-lipid apheresis Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia
Study Start Date : October 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : February 2016


Arm Intervention/treatment
Experimental: Pre-lipid apheresis
Blood samples will be taken just before the start of the lipid apheresis treatment.
Other: Pre-lipid apheresis
Blood samples will be taken just before the start of the lipid apheresis treatment.

Experimental: Post-lipid apheresis
Blood samples will be taken following the lipid apheresis treatment.
Other: Post-lipid apheresis
Blood samples will be taken following the lipid apheresis treatment.




Primary Outcome Measures :
  1. Change in mRNA expression of genes involved in cardiovascular disease using microarrays analysis. [ Time Frame: Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h) ]

Secondary Outcome Measures :
  1. Change in serum levels of C-reactive protein [ Time Frame: Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h) ]

Other Outcome Measures:
  1. Change in serum levels of vascular cell adhesion molecule [ Time Frame: Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h) ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygotes for familial hypercholesterolemia who receive lipid apheresis
  • Aged between 18-60 years

Exclusion Criteria:

  • Smokers (> 1 cigarette/day)
  • Subjects with a previous history of cardiovascular disease
  • Subjects with type 2 diabetes
  • Subjects with a monogenic dyslipidemia that it is not homozygote for familial hypercholesterolemia
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02462655


Locations
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Canada
Institute of Nutrition and Functional Foods (INAF)
Quebec, Canada, G1V 0A6
Sponsors and Collaborators
Laval University
Investigators
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Principal Investigator: Patrick Couture, MD,FRCP,PhD Laval University

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Responsible Party: Patrick Couture, MD, PHD, FRCP, Laval University
ClinicalTrials.gov Identifier: NCT02462655     History of Changes
Other Study ID Numbers: LA-PBMC
First Posted: June 4, 2015    Key Record Dates
Last Update Posted: March 8, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Inflammation
Pathologic Processes
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias