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Investigating the Effects of Lipid-therapy Intensification With Alirocumab on Endothelial Function, Carotid Arteries, Lipoprotein Particle Subfractions, Inflammation and Post-prandial Lipemia (ALIROCKS)

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ClinicalTrials.gov Identifier: NCT03559309
Recruitment Status : Recruiting
First Posted : June 18, 2018
Last Update Posted : August 27, 2019
Sponsor:
Collaborators:
numares AG
Sanofi
Information provided by (Responsible Party):
Medical University of Graz

Brief Summary:
A prospective, open-label, pilot study with 24 cardiovascular high risk patients (N=24) having insufficient Low density lipoprotein cholesterin (LDL-C) reduction despite standard of care lipid-modifying therapies (LMTs), to evaluate the effects of potent lipid-therapy intensification via the recently approved monoclonal, human anti-PCSK9 antibody Alirocumab on endothelial function, inflammation, lipoprotein particle subfractions, carotid arteries and post-prandial lipemia in clinical routine at the Medical University of Graz.

Condition or disease Intervention/treatment Phase
Atherosclerosis Hypercholesterolemia Post Prandial Lipemia Cardiovascular Diseases Diagnostic Test: Magnet Resonance Tomography, Carotid Arteries Sonography, Flow-mediated Dilation, Fat-tolerance Test, Laboratory Testing Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Pilot Study Investigating the Effects of Lipid-therapy Intensification With Alirocumab on Endothelial Function, Carotid Arteries, Lipoprotein Particle Subfractions, Inflammation and Post-prandial Lipemia in Clinical Routine
Actual Study Start Date : June 20, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

Arm Intervention/treatment
Alirocumab
Medical Treatment (Clinical Routine)
Diagnostic Test: Magnet Resonance Tomography, Carotid Arteries Sonography, Flow-mediated Dilation, Fat-tolerance Test, Laboratory Testing
Patients treated with Alirocumab in the clinical routine will have additional diagnostic tests as stated above. The clinical trial will be conducted as an open label, single arm study. The diagnostic tests will be done at baseline (BL) and after 10 weeks of treatment (W10) with Alirocumab.




Primary Outcome Measures :
  1. Change of mean carotid vessel wall fractional anisotropy (2-Dimensional Cardiovascular Magnet Resonance) by very potent lipid-therapy intensification with Alirocumab [ Time Frame: From baseline to 10 weeks of treatment ]
    Study participants will undergo a cardiovascular magnetic resonance imaging of the carotid vessels. High resolution diffusion tensor imaging (DTI) will be performed on one selected axial slice using read-out segmented EPI (rs-EPI) sequence on a 3T MR scanner.


Secondary Outcome Measures :
  1. Change of FDD (flow-dependent dilation) in response to Alirocumab [ Time Frame: From baseline to 10 weeks of treatment ]
    Vasodilation of the brachial artery will be measured with a linear array transducer, 8-13 MHz. Flow mediated dilatation is defined as the change in post-ischemic diameter as a percentage of the baseline diameter. Flow-independent vasodilatation will be evaluated by nitroglycerin-mediated dilatation. At least 15 minutes after the flow mediated procedure the brachial arterial diameter will be measured before and 3 minutes after sublingual administration of nitroglycerin (NTG 0.3 mg spray).

  2. Change of intima media thickness in response to Alirocumab [ Time Frame: From baseline to 10 weeks of treatment ]
    All ultrasound investigations will be performed at the Division of Angiology, Department of Internal Medicine, Medical University of Graz. Carotid intima-media thickness is defined as the mean of at least three different measurements of intima media thickness in a one-centimeter-long segment of the brachial common carotid artery.

  3. Change of post-prandial lipaemia in response to Alirocumab [ Time Frame: From baseline to 10 weeks of treatment ]
    Post-prandial lipaemia will be assessed with a fat-tolerance test (FTT). The participants will receive a standard fat rich meal. The Lipotest® meal is a diagnostic meal with special medical purpose, characterized as "Food for specialized diagnostic determination of postprandial triglycerides" and consists of 832 kCal total energy input (75 g saturated fat, 25 g carbohydrates, 10 g protein, 2,1 g fiber and 0,15 g salt).

  4. Change of the lipoprotein subfractions in response to Alirocumab [ Time Frame: From baseline to 10 weeks of treatment ]
    LDL-Cholesterol will not only be calculated via Friedewald formula, but all plasma lipoprotein particles will be subfractionated by ultracentrifugation / precipitation (Chylomicrons, VLDL, LDL and HDL). Plasma lipid levels will be measured enzymatically using an autoanalyzer. Particle concentrations of lipoprotein subclasses will be measured using nuclear magnetic resonance as previously described (Silbernagel et al 2017). The Apo(lipo)protein levels will be measured using immunoassays.

  5. Changes of inflammatory parameters in response to Alirocumab [ Time Frame: From baseline to 10 weeks of treatment ]
    Enzyme-linked immunosorbent assay kits will be used and C-reactive protein, as well as cytokines and adhesion molecules of special interest.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient scheduled for treatment with Alirocumab in clinical routine (after approval of cost coverage by insurance company)
  2. No previous treatment with PCSK9 antibodies
  3. Signed informed consent form

Exclusion Criteria:

  1. Age of < 18 years
  2. Pregnancy (pregnancy test at screening visit)
  3. Breast-feeding
  4. Impossibility to perform magnetic resonance imaging of the carotid artery (claustrophobia, carotid stent)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03559309


Contacts
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Contact: Priska Hirschmann, MSc. 004331638512344 priska.hirschmann@medunigraz.at

Locations
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Austria
Medical University of Graz Recruiting
Graz, Styria, Austria, A-8036
Contact: Priska Hirschmann    +43 (316) 385 - 12344    priska.hirschmann@medunigraz.at   
Principal Investigator: Günther Silbernagel, MD. Ass.Prof.         
Sponsors and Collaborators
Medical University of Graz
numares AG
Sanofi
Investigators
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Principal Investigator: Günther Silbernagel, MD. Ass.Prof. Medical University of Graz

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Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT03559309     History of Changes
Other Study ID Numbers: ALIROCKS_05MAR2018_V3
First Posted: June 18, 2018    Key Record Dates
Last Update Posted: August 27, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Arterial Occlusive Diseases
Atherosclerosis
Hypercholesterolemia
Hyperlipidemias
Inflammation
Cardiovascular Diseases
Pathologic Processes
Arteriosclerosis
Vascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs