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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Atherosclerosis; Hypercholesterolemia; Post Prandial Lipemia
• Intervention / Treatment: Diagnostic test: Magnet Resonance Tomography, Carotid Arteries Sonography, Flow-mediated Dilation, Fat-tolerance Test, Laboratory Testing

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, A-8036
      • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mean carotid vessel wall fractional anisotropy (2-Dimensional Cardiovascular Magnet Resonance) by very potent lipid-therapy intensification with Alirocumab	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.	From baseline to 10 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of FDD (flow-dependent dilation) in response to Alirocumab	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).	From baseline to 10 weeks of treatment
Change of intima media thickness in response to Alirocumab	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.	From baseline to 10 weeks of treatment
Change of post-prandial lipaemia in response to Alirocumab	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).	From baseline to 10 weeks of treatment
Change of the lipoprotein subfractions in response to Alirocumab	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.	From baseline to 10 weeks of treatment
Changes of inflammatory parameters in response to Alirocumab	Enzyme-linked immunosorbent assay kits will be used and C-reactive protein, as well as cytokines and adhesion molecules of special interest.	From baseline to 10 weeks of treatment

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Sanofi; numares AG
• Investigators: Principal Investigator: Günther Silbernagel, MD. Ass.Prof., Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2018
• Primary Completion (Actual): February 5, 2020
• Study Completion (Actual): February 5, 2020

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 5, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 21, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Dyslipidemias; Cardiovascular Diseases; Inflammation; Hypercholesterolemia; Atherosclerosis; Hyperlipidemias
• Other Study ID Numbers: ALIROCKS_05MAR2018_V3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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