Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia

Familial Hypercholesterolemia Clinical Trial

— LA-PBMC  

Official title:

Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02462655
• Other study ID #: LA-PBMC
• Status: Completed
• Phase: N/A
• First received: June 2, 2015
• Last updated: March 7, 2016
• Start date: October 2015
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Other:
• Pre-lipid apheresis
Blood samples will be taken just before the start of the lipid apheresis treatment.
• Post-lipid apheresis
Blood samples will be taken following the lipid apheresis treatment.

Locations

Country	Name	City	State
Canada	Institute of Nutrition and Functional Foods (INAF)	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Laval University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in serum levels of vascular cell adhesion molecule		Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)	No
Primary	Change in mRNA expression of genes involved in cardiovascular disease using microarrays analysis.		Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)	No
Secondary	Change in serum levels of C-reactive protein		Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)	No