Familial HypercholesterolemiaINFLAMENCT01138371

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

An observational study of Familial Hypercholesterolemia, run by Emory University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 70 years
Conditions the study is for: Familial Hypercholesterolemia
What is being tested?: LDL Apheresis
Type of treatment: Surgery or procedure
How many people: 8 participants
Where: 1 siteUnited States
Study dates: Mar 2011to Mar 2012
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 70 years
All sexes
No healthy volunteers
Child, Adult, Older adult

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

Who may be able to join

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.

Who cannot join

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

Show all 11Show fewer

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 locations and contacts

1 site in 1 country.

United States1 site

Emory University Hospital
Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Familial Hypercholesterolemia
Being tested: LDL Apheresis
Keywords: LDL apheresis, Familial hypercholesterolemia, Inflammatory markers, Hyperlipidemia, Cardiovascular disease
Medical subject headings: Hyperlipoproteinemia Type II, Hyperlipidemias, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LDL ApheresisProcedure or surgery
Also called Apheresis, LDL filtration
LDL Apheresis

Study groups in NCT01138371
Study group	Role	What they receive
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 Receives: Procedure: LDL Apheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
Measured: 1 month

Secondary outcomes (1)

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.
Measured: 2 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2011Mar 2012

First posted7 Jun 2010 (estimated)
Study startMar 2011
Primary completionFeb 2012
Study completionMar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (14)Papers the sponsor has linked to this study.
Other trials for Familial HypercholesterolemiaStudies of the same condition, open and under way.
More trials run by Emory UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case only
Time perspective: Prospective
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01138371
Sponsor's protocol ID: IRB00044778
Other IDs: INFLAME_EUH
Acronym: INFLAME
Status last verified: Dec 2013
First submitted: 4 Jun 2010
Last updated: 17 Dec 2013
Results posted: No
Data monitoring committee: Yes

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.
PubMed 9141382
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.
PubMed 19627661
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.
PubMed 15172629
Thompson GR. LDL apheresis. Atherosclerosis. 2003 Mar;167(1):1-13. doi: 10.1016/s0021-9150(02)00251-4.
PubMed 12618263
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.
PubMed 7898227
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.
PubMed 8635262
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.
PubMed 15095396
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.
PubMed 8994420
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.
PubMed 15880405
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.
PubMed 15878003
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.
PubMed 15186959
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.
PubMed 12918586
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.
PubMed 19927364
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.
PubMed 12887727

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
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Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Not yet recruitingObservational study
An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia
Hypercholesterolaemia, Familial Hypercholesterolaemia
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia

All Familial Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Inflammatory and Lipid Markers Pre- and Post-LDL Apheresis: A Multicenter Experience
ClinicalTrials.gov ID: NCT01138371
Acronym / sponsor ID: INFLAME / IRB00044778
Conditions: Familial Hypercholesterolemia
Keywords: LDL apheresis, Familial hypercholesterolemia, Inflammatory markers, Hyperlipidemia, Cardiovascular disease
Study type: Observational
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Emory UniversityUniversity, hospital or other
Collaborators: Kaneka Medical America LLC
Study start: Mar 2011
Primary completion: Feb 2012 (actual)
Study completion: Mar 2012 (actual)
First posted: 7 Jun 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Case only
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Familial hypercholesterolemia	–	Procedure: LDL Apheresis* 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

Who may qualify

Ages: 3 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: This study focuses on people who are currently on stable LDL apheresis treatment for high cholesterol.

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LDL ApheresisAlso: Apheresis, LDL filtrationLDL Apheresis	Procedure or surgery	Familial hypercholesterolemia

Primary outcome

Lipid Marker Change
Time frame: 1 month
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
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 secondary outcome

Inflammatory Marker Rebound
Time frame: 2 days

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2013.
Background: PubMed 9141382Napoli 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.
Background: PubMed 19627661Mehta 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.
Background: PubMed 15172629Mabuchi 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.
Background: PubMed 12618263Thompson GR. LDL apheresis. Atherosclerosis. 2003 Mar;167(1):1-13. doi: 10.1016/s0021-9150(02)00251-4.
Background: PubMed 7898227Thompson 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.
Background: PubMed 8635262Kroon 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.
Background: PubMed 15095396Igarashi 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.
Background: PubMed 8994420Tamai 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.
Background: PubMed 15880405Kobayashi 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.
Background: PubMed 15878003Moriarty 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.
Background: PubMed 15186959Wang 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.
Background: PubMed 12918586Nakamura 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.

Related trials for Familial Hypercholesterolemia

Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Not yet recruitingObservational study
An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia
Hypercholesterolaemia, Familial Hypercholesterolaemia
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Laurence Sperling, MD principal investigator

Emory University

Vimal Ramjee, MD study director

Emory University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Familial Hypercholesterolemia, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lipid Marker Change (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01138371, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2013.