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

Inflammatory and Lipid Markers Pre- and Post-LDL Apheresis: A Multicenter Experience

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.

Study Overview

• Status: Completed
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Procedure: LDL Apheresis

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.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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: Apheresis; LDL filtration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Marker Change	We will measure the level of cholesterol markers in your blood before and after the LDL apheresis procedure with a blood draw.	1 month
Inflammatory Marker Change	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)	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Marker Rebound	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.	2 days

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Kaneka Medical America LLC
• Investigators: Principal Investigator: Laurence Sperling, MD, Emory University; Study Director: Vimal Ramjee, MD, Emory University

Publications and helpful links

General Publications

• Napoli C, Ambrosio G, Scarpato N, Corso G, Palumbo G, D'Armiento FP, Mancini FP, Malorni A, Formisano S, Ruocco A, Cali 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. doi: 10.1016/s0002-8703(97)70155-8.
• 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. doi: 10.1007/s11936-009-0029-1.
• 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. doi: 10.1016/j.transci.2004.01.006.
• Thompson GR. LDL apheresis. Atherosclerosis. 2003 Mar;167(1):1-13. doi: 10.1016/s0021-9150(02)00251-4.
• 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. doi: 10.1016/s0140-6736(95)92961-4.
• 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. doi: 10.1161/01.cir.93.10.1826.
• 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. doi: 10.1002/jca.20000.
• 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. doi: 10.1161/01.cir.95.1.76.
• 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. doi: 10.1002/jca.20033.
• 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. doi: 10.1016/j.amjcard.2005.01.058.
• 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. doi: 10.1016/j.atherosclerosis.2004.03.011.
• 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, Lappegard KT. Different inflammatory responses induced by three LDL-lowering apheresis columns. J Clin Apher. 2009;24(6):247-53. doi: 10.1002/jca.20223.
• 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. doi: 10.1046/j.1526-0968.2003.00080.x.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: June 4, 2010
• First Submitted That Met QC Criteria: June 4, 2010
• First Posted (Estimate): June 7, 2010

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: December 16, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Cardiovascular disease; LDL apheresis; Familial hypercholesterolemia; Inflammatory markers; Hyperlipidemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: IRB00044778; INFLAME_EUH (Other Identifier: Other)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No