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

Familial Hypercholesterolemia Clinical Trial

— INFLAME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01138371
• Other study ID #: IRB00044778
• Secondary ID: INFLAME_EUH
• Status: Completed
• Phase: N/A
• First received: June 4, 2010
• Last updated: December 16, 2013
• Start date: March 2011
• Est. completion date: March 2012

Study information

• Verified date: December 2013
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 70 Years

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Procedure:
• LDL Apheresis
LDL Apheresis

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Kaneka Pharma America LLC

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. doi: 10.1002/jca.20223. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No