Familial HypercholesterolemiaLA-PBMCNCT02462655
Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia
A study testing Pre-lipid apheresis and Post-lipid apheresis in people with Familial Hypercholesterolemia, run by Laval University at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Familial Hypercholesterolemia
- What is being tested?
- Pre-lipid apheresis and Post-lipid apheresis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2015to Feb 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Homozygotes for familial hypercholesterolemia who receive lipid apheresis
- Aged between 18-60 years
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Institute of Nutrition and Functional Foods (INAF)
Québec, Quebec, G1V 0A6
About this study
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
- Being tested
- Pre-lipid apheresis, Post-lipid apheresis
- Medical subject headings
- Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-lipid apheresisOther
Blood samples will be taken just before the start of the lipid apheresis treatment.
Post-lipid apheresisOther
Blood samples will be taken following the lipid apheresis treatment.
| Study group | Role | What they receive |
|---|---|---|
| Pre-lipid apheresis | Experimental | Blood samples will be taken just before the start of the lipid apheresis treatment. Receives: Other: Pre-lipid apheresis |
| Post-lipid apheresis | Experimental | Blood samples will be taken following the lipid apheresis treatment. Receives: Other: Post-lipid apheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mRNA expression of genes involved in cardiovascular disease using microarrays analysis.
Measured: Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)
Secondary outcomes (1)
Change in serum levels of C-reactive protein
Measured: Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startOct 2015
- Primary completionDec 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Laval UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laval University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Patrick Couture, Laval University
- Investigators
- Patrick Couture, MD,FRCP,PhD, Principal investigator, Laval University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02462655
- Sponsor's protocol ID
- LA-PBMC
- Acronym
- LA-PBMC
- Status last verified
- Mar 2016
- First submitted
- 2 Jun 2015
- Last updated
- 8 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT02462655
- Acronym / sponsor ID
- LA-PBMC / LA-PBMC
- Conditions
- Familial Hypercholesterolemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Laval UniversityUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pre-lipid apheresis | Experimental | Other: Pre-lipid apheresisBlood samples will be taken just before the start of the lipid apheresis treatment. |
| Post-lipid apheresis | Experimental | Other: Post-lipid apheresisBlood samples will be taken following the lipid apheresis treatment. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Homozygotes for familial hypercholesterolemia who receive lipid apheresis
- Aged between 18-60 years
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pre-lipid apheresisBlood samples will be taken just before the start of the lipid apheresis treatment. | Other | Pre-lipid apheresis |
| Post-lipid apheresisBlood samples will be taken following the lipid apheresis treatment. | Other | Post-lipid apheresis |
Primary outcome
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)
1 secondary outcome
Change in serum levels of C-reactive protein
Time frame: Pre-lipid apheresis (t=0h) and post-lipid apheresis (t=3h)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2016.
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Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Couture, MD,FRCP,PhD principal investigator
Laval University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pre-lipid apheresis and Post-lipid apheresis in people with Familial Hypercholesterolemia, run by Laval University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2016.