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

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
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
NCT ID
NCT03393377
First Posted
December 29, 2017
Last Updated
January 5, 2018
Sponsor
University Medical Centre Ljubljana
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
Citations:
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Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination
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