Effects of Low-density Lipoprotein (LDL) Apheresis on Inflammatory and Lipid Markers - Full Text View

Purpose

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.

Condition	Intervention
Familial Hypercholesterolemia	Procedure: LDL Apheresis

Study Type:	Observational
Study Design:	Observational Model: Case-Only Time Perspective: Prospective
Official Title:	Inflammatory and Lipid Markers Pre- and Post-LDL Apheresis: A Multicenter Experience

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis hypercholesterolemia

MedlinePlus related topics: Cholesterol

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:

Lipid Marker Change [ Time Frame: 1 month ] [ Designated as safety issue: No ]
We will measure the level of cholesterol markers in your blood before and after the LDL apheresis procedure with a blood draw.
Inflammatory Marker Change [ Time Frame: 1 month ] [ Designated as safety issue: No ]
We will measure the level of inflammatory markers in your blood before and after the LDL apheresis procedure with blood draws (for 2 apheresis sessions)

Secondary Outcome Measures:

Inflammatory Marker Rebound [ Time Frame: 2 days ] [ Designated as safety issue: No ]
We will measure the level of inflammatory markers in your blood after LDL apheresis procedure the following morning, 24 hours after procedure, and on the second morning.

Biospecimen Retention: Samples Without DNA

Blood samples only

Enrollment:	8
Study Start Date:	March 2011
Study Completion Date:	March 2012
Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Familial hypercholesterolemia 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	Procedure: LDL Apheresis LDL Apheresis Other Names: LDL Apheresis Apheresis LDL filtration

Groups/Cohorts

Assigned Interventions

Familial hypercholesterolemia

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

Procedure: LDL Apheresis

LDL Apheresis

Other Names:

LDL Apheresis
Apheresis
LDL filtration

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

Ages Eligible for Study:	3 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

This study focuses on people who are currently on stable LDL apheresis treatment for high cholesterol.

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01138371

Locations

United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Kaneka Pharma America Corporation

Investigators

Principal Investigator:	Laurence Sperling, MD	Emory University
Study Director:	Vimal Ramjee, MD	Emory University

More Information

Publications:

Napoli C, Ambrosio G, Scarpato N, Corso G, Palumbo G, D'Armiento FP, Mancini FP, Malorni A, Formisano S, Ruocco A, Calí A, Chiariello M. Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia. Am Heart J. 1997 May;133(5):585-95.

Mehta PK, Baer J, Nell C, Sperling LS. Low-density lipoprotein apheresis as a treatment option for hyperlipidemia. Curr Treat Options Cardiovasc Med. 2009 Aug;11(4):279-88.

Mabuchi H, Higashikata T, Kawashiri MA. Clinical applications of long-term LDL-apheresis on and beyond refractory hypercholesterolemia. Transfus Apher Sci. 2004 Jun;30(3):233-43. Review.

Thompson GR. LDL apheresis. Atherosclerosis. 2003 Mar;167(1):1-13. Review.

Thompson GR, Maher VM, Matthews S, Kitano Y, Neuwirth C, Shortt MB, Davies G, Rees A, Mir A, Prescott RJ, et al. Familial Hypercholesterolaemia Regression Study: a randomised trial of low-density-lipoprotein apheresis. Lancet. 1995 Apr 1;345(8953):811-6.

Kroon AA, Aengevaeren WR, van der Werf T, Uijen GJ, Reiber JH, Bruschke AV, Stalenhoef AF. LDL-Apheresis Atherosclerosis Regression Study (LAARS). Effect of aggressive versus conventional lipid lowering treatment on coronary atherosclerosis. Circulation. 1996 May 15;93(10):1826-35.

Igarashi K, Tsuji M, Nishimura M, Horimoto M. Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia. J Clin Apher. 2004;19(1):11-6.

Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T. Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation. 1997 Jan 7;95(1):76-82.

Kobayashi S, Moriya H, Maesato K, Okamoto K, Ohtake T. LDL-apheresis improves peripheral arterial occlusive disease with an implication for anti-inflammatory effects. J Clin Apher. 2005 Dec;20(4):239-43.

Moriarty PM, Gibson CA. Effect of low-density lipoprotein apheresis on lipoprotein-associated phospholipase A2. Am J Cardiol. 2005 May 15;95(10):1246-7.

Wang Y, Blessing F, Walli AK, Uberfuhr P, Fraunberger P, Seidel D. Effects of heparin-mediated extracorporeal low-density lipoprotein precipitation beyond lowering proatherogenic lipoproteins--reduction of circulating proinflammatory and procoagulatory markers. Atherosclerosis. 2004 Jul;175(1):145-50.

Nakamura T, Matsuda T, Suzuki Y, Ueda Y, Koide H. Effects of low-density lipoprotein apheresis on plasma matrix metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans. ASAIO J. 2003 Jul-Aug;49(4):430-4.

Hovland A, Hardersen R, Sexton J, Mollnes TE, Lappegård KT. Different inflammatory responses induced by three LDL-lowering apheresis columns. J Clin Apher. 2009;24(6):247-53.

Kojima S, Shida M, Yokoyama H. Changes in C-reactive protein plasma levels during low-density lipoprotein apheresis. Ther Apher Dial. 2003 Aug;7(4):431-4.

Responsible Party:	Vimal Ramjee, Junior Investigator, Emory University
ClinicalTrials.gov Identifier:	NCT01138371 History of Changes
Other Study ID Numbers:	INFLAME_EUH
Study First Received:	June 4, 2010
Last Updated:	March 27, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

LDL apheresis
Familial hypercholesterolemia
Inflammatory markers
Hyperlipidemia
Cardiovascular disease

Additional relevant MeSH terms:

Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders

Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias

ClinicalTrials.gov processed this record on May 16, 2013

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