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

This study has been completed.
Sponsor:
Collaborator:
Kaneka Pharma America Corporation
Information provided by (Responsible Party):
Emory University
ClinicalTrials.gov Identifier:
NCT01138371
First received: June 4, 2010
Last updated: December 16, 2013
Last verified: December 2013
  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:


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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

Responsible Party: Emory University
ClinicalTrials.gov Identifier: NCT01138371     History of Changes
Other Study ID Numbers: IRB00044778, INFLAME_EUH
Study First Received: June 4, 2010
Last Updated: December 16, 2013
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 July 22, 2014