Clinical trial NCT01138371: Effects of Low-density Lipoprotein (LDL) Apheresis on Inflammatory and Lipid Markers
Official title: Inflammatory and Lipid Markers Pre- and Post-LDL Apheresis: A Multicenter Experience
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Familial Hypercholesterolemia
Keywords: LDL apheresis
Familial hypercholesterolemia
Inflammatory markers
Hyperlipidemia
Cardiovascular disease
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Kaneka Medical America LLC
First posted: 2010-06-07
Enrollment: 8
Sex: ALL
Minimum age (years): 3
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study focuses on people who are currently on stable LDL apheresis treatment for high cholesterol.

Brief summary: The primary objective of this study is to measure how LDL apheresis affects levels of inflammatory and cholesterol markers in human beings. The investigators will address this question by drawing pre- and post-LDL apheresis blood from patients who are undergoing this procedure. A secondary objective of this study is to learn how specific inflammatory markers behave in our blood in terms of time to rebound back to normal levels. The investigators will address this question by drawing post-LDL apheresis blood at predetermined time intervals.

Detailed description: Numerous epidemiological investigations have demonstrated the importance of cholesterol - specifically low density lipoprotein (LDL) - in the development and progression of atherosclerosis. A continuing relationship between cholesterol level and coronary morbidity has been established. The initial approach for managing elevated cholesterol includes lifestyle interventions, namely eating a low fat diet, weight loss in overweight patients, and regular aerobic exercise. Once lifestyle interventions have been applied, pharmacologic therapy becomes a mainstay of therapy, conventionally with a statin followed by adjunctive medicines as indicated. Certain populations that are refractory to aggressive pharmacotherapy, however - such as patients who have familial hypercholesterolemia (FH) - necessitate alternative means of lipid management. Therapeutic considerations in these patients include LDL apheresis and a number of rare procedures such as partial ileal bypass, liver transplantation, portocaval shunting, and possibly gene therapy in the future.

The anti-inflammatory effects of LDL apheresis and its effects on endothelial function are not well known. Considering several pathways of atherogenesis, and inflammation as a central mechanism thereof, LDL apheresis may theoretically provide synergistic benefit of lipid lowering as well as proinflammatory agent lowering that can lead to significantly decreased atherogenesis. This study looks to address these questions by assessing the effects of LDL apheresis on inflammatory and lipid markers.

Eligibility criteria: Inclusion criteria:

* Heterozygous FH with documented CAD and LDL-C ≥ 200 mg/dL Documented CAD may be represented as: Lesion(s) on coronary angiography, history of myocardial infarction, CABG, PTCA, progressive angina demonstrated by stress testing, history of other revascularization procedure (e.g. atherectomy)
* Homozygous FH and LDL-C \> 500 mg/dL
* Heterozygous FH and LDL-C ≥ 300 mg/dL
* On stable LDL apheresis therapy for at least 6 months.

Exclusion criteria:

* Patient refusal to participate
* Inability to attend 2 consecutive LDL apheresis sessions for study duration
* Subject with advanced renal disease
* Subject with chronic progressive hepatic disease and demonstrated deficient synthetic function
* Subject with acute hepatic process
* Subject with current malignancy
* Subject with diagnosis of amyloidosis
* Subject with diagnosis of rheumatoid arthritis
* Any subject with acute flare of chronic disease
* Subject with recent ethanol ingestion
* Subject with significant bone disease

Primary outcomes:
measure: Lipid Marker Change
timeFrame: 1 month
measure: Inflammatory Marker Change
timeFrame: 1 month
Secondary outcomes:
measure: Inflammatory Marker Rebound
timeFrame: 2 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Laurence Sperling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Vimal Ramjee, MD
role: STUDY_DIRECTOR
References:
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