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

Cardiovascular Diseases Clinical Trial

— ALIROCKS  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03559309
• Other study ID #: ALIROCKS_05MAR2018_V3
• Status: Terminated
• Phase: Phase 4
• Start date: June 20, 2018
• Est. completion date: February 5, 2020

Study information

• Verified date: April 2020
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: February 5, 2020
• Est. primary completion date: February 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Hypercholesterolemia
• Hyperlipidemias
• Inflammation
• Post Prandial Lipemia

Intervention

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.

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz	Styria

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Graz	numares AG, Sanofi

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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