Effects of Low-density Lipoprotein (LDL) Apheresis on Inflammatory and Lipid Markers (INFLAME)

Emory University

Status: Completed

Conditions: Familial Hypercholesterolemia

Treatments: Procedure: LDL Apheresis

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT01138371

IRB00044778

INFLAME_EUH (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 3 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

8 participants in 1 patient group

Familial hypercholesterolemia

Description:

* 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) * 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

Treatment:

Procedure: LDL Apheresis