4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

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

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

Study Description
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

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
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
Actual Primary Completion Date : February 5, 2020
Actual Study Completion Date : February 5, 2020
Arms and Interventions
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.
Outcome Measures
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.


Eligibility Criteria
Layout table for eligibility information
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)
Contacts and Locations

Locations
Layout table for location information
Austria
Medical University of Graz
Graz, Styria, Austria, A-8036
Sponsors and Collaborators
Medical University of Graz
numares AG
Sanofi
Investigators
Layout table for investigator information
Principal Investigator: Günther Silbernagel, MD. Ass.Prof. Medical University of Graz
Tracking Information
First Submitted Date  ICMJE May 22, 2018
First Posted Date  ICMJE June 18, 2018
Last Update Posted Date April 24, 2020
Actual Study Start Date  ICMJE June 20, 2018
Actual Primary Completion Date February 5, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2018) 		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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2018)
  • 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).
  • 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.
  • 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).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigating the Effects of Lipid-therapy Intensification With Alirocumab on Endothelial Function, Carotid Arteries, Lipoprotein Particle Subfractions, Inflammation and Post-prandial Lipemia
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Atherosclerosis
  • Hypercholesterolemia
  • Post Prandial Lipemia
  • Cardiovascular Diseases
Intervention  ICMJE 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.
Study Arms  ICMJE Alirocumab
Medical Treatment (Clinical Routine)
Intervention: Diagnostic Test: Magnet Resonance Tomography, Carotid Arteries Sonography, Flow-mediated Dilation, Fat-tolerance Test, Laboratory Testing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 5, 2018) 		24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 5, 2020
Actual Primary Completion Date February 5, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03559309
Other Study ID Numbers  ICMJE ALIROCKS_05MAR2018_V3
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Medical University of Graz
Study Sponsor  ICMJE Medical University of Graz
Collaborators  ICMJE
  • numares AG
  • Sanofi
Investigators  ICMJE
Principal Investigator: Günther Silbernagel, MD. Ass.Prof. Medical University of Graz
PRS Account Medical University of Graz
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯