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

NCT03393377 | Completed

• 1 other identifier: AGE-ZT
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Atherosclerosis

Keywords

arterial stiffness; endothelial dysfunction; fluvastatin; valsartan; inflammatory markers; oxidative stress; SIRT1

Outcome Measures

Primary Outcomes (14)

• brachial flow-mediated dilatation (FMD)

  FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)

  30 days

• reactive hyperaemia index (RHI)

  RHI measured by Endopat device

  30 days

• beta stiffness coefficient

  assessed by ultrasound employing e-Tracking on right common carotid artery

  30 days

• carotid pulse wave velocity (c-PWV)

  assessed by ultrasound employing e-Tracking on right common carotid artery

  30 days

• carotid-femoral PWV (cf-PWV)

  cf-PWV measured by Sphygmocor device

  30 days

• high-sensitivity C-reactive protein (hs-CRP)

  inflammatory marker

  30 days

• interleukin 6 (IL-6)

  inflammatory marker

  30 days

• vascular cell adhesion molecule 1 (VCAM1)

  inflammatory marker

  30 days

• total antioxidant status (TAS)

  marker of oxidative stress

  30 days

• gene SIRT1

  Hs01009006\_m1

  30 days

• gene mTOR

  Hs00234522\_m1

  30 days

• gene NF-kB1

  Hs00765730\_m1

  30 days

• gene Nrf2/NFE2L2

  Hs00975961\_g1

  30 days

• gene AMPK/PRKAA1

  Hs01562315\_m1

  30 days

Secondary Outcomes (5)

• brachial flow-mediated dilatation (FMD)

  10 weeks after treatment completion

• reactive hyperaemia index (RHI)

  10 weeks after treatment completion

• beta stiffness coefficient

  10 weeks after treatment completion

• carotid pulse wave velocity (c-PWV)

  10 weeks after treatment completion

• carotid-femoral PWV (cf-PWV)

  10 weeks after treatment completion

Study Arms (2)

intervention group

EXPERIMENTAL

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

Drug: fluvastatin 10 mg and valsartan 20 mg

control group

PLACEBO COMPARATOR

received placebo for 30 days

Drug: placebo

Interventions

fluvastatin 10 mg and valsartan 20 mg DRUG

Also known as: low-flu/val

intervention group

placebo DRUG

control group

Eligibility Criteria

• Age: 40 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Related Publications (10)

• Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available.

  PMID: 27222591 BACKGROUND

• Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2015 Nov 13;4(11):e002270. doi: 10.1161/JAHA.115.002270.

  PMID: 26567372 BACKGROUND

• Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061.

  PMID: 20338492 BACKGROUND

• Paneni F, Diaz Canestro C, Libby P, Luscher TF, Camici GG. The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels. J Am Coll Cardiol. 2017 Apr 18;69(15):1952-1967. doi: 10.1016/j.jacc.2017.01.064.

  PMID: 28408026 BACKGROUND

• Lunder M, Janic M, Jug B, Sabovic M. The effects of low-dose fluvastatin and valsartan combination on arterial function: a randomized clinical trial. Eur J Intern Med. 2012 Apr;23(3):261-6. doi: 10.1016/j.ejim.2011.11.011. Epub 2011 Dec 12.

  PMID: 22385885 BACKGROUND

• Boncelj Svetek M, Erzen B, Kanc K, Sabovic M. Impaired endothelial function and arterial stiffness in patients with type 2 diabetes - The effect of a very low-dose combination of fluvastatin and valsartan. J Diabetes Complications. 2017 Mar;31(3):544-550. doi: 10.1016/j.jdiacomp.2016.12.002. Epub 2016 Dec 16.

  PMID: 28012835 BACKGROUND

• Janic M, Lunder M, Prezelj M, Sabovic M. A combination of low-dose fluvastatin and valsartan decreases inflammation and oxidative stress in apparently healthy middle-aged males. J Cardiopulm Rehabil Prev. 2014 May-Jun;34(3):208-12. doi: 10.1097/HCR.0000000000000027.

  PMID: 24263076 BACKGROUND

• Sosnowska B, Mazidi M, Penson P, Gluba-Brzozka A, Rysz J, Banach M. The sirtuin family members SIRT1, SIRT3 and SIRT6: Their role in vascular biology and atherogenesis. Atherosclerosis. 2017 Oct;265:275-282. doi: 10.1016/j.atherosclerosis.2017.08.027. Epub 2017 Aug 26.

  PMID: 28870631 BACKGROUND

• Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, Pais P, Lopez-Jaramillo P, Leiter LA, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Peters RJ, Held C, Chazova I, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Sanchez-Vallejo G, McKelvie R, Pogue J, Jung H, Gao P, Diaz R, Lonn E; HOPE-3 Investigators. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2021-31. doi: 10.1056/NEJMoa1600176. Epub 2016 Apr 2.

  PMID: 27040132 BACKGROUND

• Robinson JG, Gidding SS. Curing atherosclerosis should be the next major cardiovascular prevention goal. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt A):2779-85. doi: 10.1016/j.jacc.2014.04.009. Epub 2014 May 7.

  PMID: 24814489 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis

Interventions

Fluvastatin; Valsartan

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: December 29, 2017
• First Posted: January 8, 2018
• Study Start: September 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2017
• Last Updated: January 8, 2018

Record last verified: 2018-01