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

NCT02462655 | Completed

• 1 other identifier: LA-PBMC
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Change in mRNA expression of genes involved in cardiovascular disease using microarrays analysis.

  Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)

Secondary Outcomes (1)

• Change in serum levels of C-reactive protein

  Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)

Other Outcomes (1)

• Change in serum levels of vascular cell adhesion molecule

  Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)

Study Arms (2)

Pre-lipid apheresis

EXPERIMENTAL

Blood samples will be taken just before the start of the lipid apheresis treatment.

Other: Pre-lipid apheresis

Post-lipid apheresis

EXPERIMENTAL

Blood samples will be taken following the lipid apheresis treatment.

Other: Post-lipid apheresis

Interventions

Pre-lipid apheresis OTHER

Blood samples will be taken just before the start of the lipid apheresis treatment.

Pre-lipid apheresis

Post-lipid apheresis OTHER

Blood samples will be taken following the lipid apheresis treatment.

Post-lipid apheresis

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laval University: lead

Study Sites (1)

Institute of Nutrition and Functional Foods (INAF)

Québec, Quebec, G1V 0A6, Canada

Location

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Patrick Couture, MD,FRCP,PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD, FRCP

Study Record Dates

• First Submitted: June 2, 2015
• First Posted: June 4, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: March 8, 2016

Record last verified: 2016-03

Locations

CA (1)