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Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination (AGE-ZT)

Primary Purpose

Atherosclerosis

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
fluvastatin 10 mg and valsartan 20 mg
placebo
Sponsored by
University Medical Centre Ljubljana
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Atherosclerosis focused on measuring arterial stiffness, endothelial dysfunction, fluvastatin, valsartan, inflammatory markers, oxidative stress, SIRT1

Eligibility Criteria

40 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • moderate cardiovascular risk according to Systematic Coronary Risk Estimation (SCORE) risk charts of the European Society of Cardiology
  • males
  • aged between 40 and 55 years

Exclusion Criteria:

  • diabetes mellitus
  • manifest peripheral artery disease or carotid artery disease
  • acute infection
  • chronic diseases
  • present therapy with fluvastatin and/or valsartan

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    intervention group

    control group

    Arm Description

    received fluvastatin 10 mg and valsartan 20 mg (low-flu/val) for 30 days

    received placebo for 30 days

    Outcomes

    Primary Outcome Measures

    brachial flow-mediated dilatation (FMD)
    FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)
    reactive hyperaemia index (RHI)
    RHI measured by Endopat device
    beta stiffness coefficient
    assessed by ultrasound employing e-Tracking on right common carotid artery
    carotid pulse wave velocity (c-PWV)
    assessed by ultrasound employing e-Tracking on right common carotid artery
    carotid-femoral PWV (cf-PWV)
    cf-PWV measured by Sphygmocor device
    high-sensitivity C-reactive protein (hs-CRP)
    inflammatory marker
    interleukin 6 (IL-6)
    inflammatory marker
    vascular cell adhesion molecule 1 (VCAM1)
    inflammatory marker
    total antioxidant status (TAS)
    marker of oxidative stress
    gene SIRT1
    Hs01009006_m1
    gene mTOR
    Hs00234522_m1
    gene NF-kB1
    Hs00765730_m1
    gene Nrf2/NFE2L2
    Hs00975961_g1
    gene AMPK/PRKAA1
    Hs01562315_m1

    Secondary Outcome Measures

    brachial flow-mediated dilatation (FMD)
    FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)
    reactive hyperaemia index (RHI)
    RHI measured by Endopat device
    beta stiffness coefficient
    assessed by ultrasound employing e-Tracking on right common carotid artery
    carotid pulse wave velocity (c-PWV)
    assessed by ultrasound employing e-Tracking on right common carotid artery
    carotid-femoral PWV (cf-PWV)
    cf-PWV measured by Sphygmocor device

    Full Information

    First Posted
    December 29, 2017
    Last Updated
    January 5, 2018
    Sponsor
    University Medical Centre Ljubljana
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03393377
    Brief Title
    Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination
    Acronym
    AGE-ZT
    Official Title
    Preventive Arterial Wall Phenotype in Subjects at Moderate Cardiovascular Risk Induced by Very Low-dose Fluvastatin/Valsartan Combination: a Pilot Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2014 (Actual)
    Primary Completion Date
    June 2015 (Actual)
    Study Completion Date
    June 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University Medical Centre Ljubljana

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The study was designed to test whether short-term treatment with a very low-dose combination of fluvastatin and valsartan could induce improvement of endothelial function, arterial stiffness, vascular inflammation, oxidative stress and expression of protective genes in subjects with moderate cardiovascular risk.
    Detailed Description
    The largest population that suffers from cardiovascular events are subjects at moderate cardiovascular risk. However, no effective and safe preventive treatment is available for this population. This study aimed to investigate whether their arterial wall phenotype could be turned to a preventive direction by low-dose fluvastatin/valsartan combination (low-flu/val). Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomised into the intervention group (n=10, low-flu/val: 10 mg/20mg) or control group (n=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), beta stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, reactive hyperaemia index, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1, total antioxidant status and expression of several protective genes (SIRT1, mTOR, NF-κB1, NFE2L2, PRKAA1) were followed.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Atherosclerosis
    Keywords
    arterial stiffness, endothelial dysfunction, fluvastatin, valsartan, inflammatory markers, oxidative stress, SIRT1

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    20 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    intervention group
    Arm Type
    Experimental
    Arm Description
    received fluvastatin 10 mg and valsartan 20 mg (low-flu/val) for 30 days
    Arm Title
    control group
    Arm Type
    Placebo Comparator
    Arm Description
    received placebo for 30 days
    Intervention Type
    Drug
    Intervention Name(s)
    fluvastatin 10 mg and valsartan 20 mg
    Other Intervention Name(s)
    low-flu/val
    Intervention Type
    Drug
    Intervention Name(s)
    placebo
    Primary Outcome Measure Information:
    Title
    brachial flow-mediated dilatation (FMD)
    Description
    FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)
    Time Frame
    30 days
    Title
    reactive hyperaemia index (RHI)
    Description
    RHI measured by Endopat device
    Time Frame
    30 days
    Title
    beta stiffness coefficient
    Description
    assessed by ultrasound employing e-Tracking on right common carotid artery
    Time Frame
    30 days
    Title
    carotid pulse wave velocity (c-PWV)
    Description
    assessed by ultrasound employing e-Tracking on right common carotid artery
    Time Frame
    30 days
    Title
    carotid-femoral PWV (cf-PWV)
    Description
    cf-PWV measured by Sphygmocor device
    Time Frame
    30 days
    Title
    high-sensitivity C-reactive protein (hs-CRP)
    Description
    inflammatory marker
    Time Frame
    30 days
    Title
    interleukin 6 (IL-6)
    Description
    inflammatory marker
    Time Frame
    30 days
    Title
    vascular cell adhesion molecule 1 (VCAM1)
    Description
    inflammatory marker
    Time Frame
    30 days
    Title
    total antioxidant status (TAS)
    Description
    marker of oxidative stress
    Time Frame
    30 days
    Title
    gene SIRT1
    Description
    Hs01009006_m1
    Time Frame
    30 days
    Title
    gene mTOR
    Description
    Hs00234522_m1
    Time Frame
    30 days
    Title
    gene NF-kB1
    Description
    Hs00765730_m1
    Time Frame
    30 days
    Title
    gene Nrf2/NFE2L2
    Description
    Hs00975961_g1
    Time Frame
    30 days
    Title
    gene AMPK/PRKAA1
    Description
    Hs01562315_m1
    Time Frame
    30 days
    Secondary Outcome Measure Information:
    Title
    brachial flow-mediated dilatation (FMD)
    Description
    FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)
    Time Frame
    10 weeks after treatment completion
    Title
    reactive hyperaemia index (RHI)
    Description
    RHI measured by Endopat device
    Time Frame
    10 weeks after treatment completion
    Title
    beta stiffness coefficient
    Description
    assessed by ultrasound employing e-Tracking on right common carotid artery
    Time Frame
    10 weeks after treatment completion
    Title
    carotid pulse wave velocity (c-PWV)
    Description
    assessed by ultrasound employing e-Tracking on right common carotid artery
    Time Frame
    10 weeks after treatment completion
    Title
    carotid-femoral PWV (cf-PWV)
    Description
    cf-PWV measured by Sphygmocor device
    Time Frame
    10 weeks after treatment completion

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: moderate cardiovascular risk according to Systematic Coronary Risk Estimation (SCORE) risk charts of the European Society of Cardiology males aged between 40 and 55 years Exclusion Criteria: diabetes mellitus manifest peripheral artery disease or carotid artery disease acute infection chronic diseases present therapy with fluvastatin and/or valsartan

    12. IPD Sharing Statement

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    Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination

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