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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002060-17 | EudraCT Number |
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| Name | Class |
|---|---|
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
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The conduit arteries exhibit a viscoelastic behavior. Visco-elasticity is partially regulated by endothelium and contributes to the optimization of the heart-vessel coupling. Aging or high resting heart rate (HR) could alter visco-elastic properties leading to increase stiffness of the conduit arteries, an independent cardiovascular risk factor, and degradation of heart-vessel coupling. Lowering HR with ivabradine could reduce these effects.
The objective of this study is to assess the effect of HR reduction by repeated administration of ivabradine on visco-elastic properties, vascular geometry and function of common carotid artery, and on cardiovascular hemodynamic in healthy subject. The influence of aging on ivabradine effects are studied too.
30 healthy volunteers aged between 25 and 65 years old, with a HR ≥ 70 bpm, will receive ivabradine or placebo during 8 days in a single center, randomized, cross-group, double blinded, placebo-controlled study. Each period of treatment will be separate by 12 to 16 days of wash-out. Each subject will participate in an exploration visit, including evaluation of visco-elastic properties, vascular geometry and function of common carotid artery, and cardiovascular hemodynamic, before and after ivabradine or placebo taking.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ivabradine-placebo | Other | Volunteers will receive, at meal, ivabradine 5 mg morning and evening for the first period of treatment during 8 days (1 capsule on day 1 and then 1 capsule 2 times a day from day 2 to day 7 and 1 capsule on day 8). A wash out period (12 to 16 days) will follow this first period of treatment. of wash-out . Then, volunteers will receive, at meal, lactose capsule (placebo) morning and evening for the first period of treatment during 8 days (1 capsule on day 1 and then 1 capsule 2 times a day from day 2 to day 7 and 1 capsule on day 8). |
|
| placebo-ivabradine | Other | Volunteers will receive, at meal, lactose capsule (placebo) morning and evening for the first period of treatment during 8 days (1 capsule on day 1 and then 1 capsule 2 times a day from day 2 to day 7 and 1 capsule on day 8). A wash out period (12 to 16 days) will follow this first period of treatment. of wash-out . Then, volunteers will receive, at meal, ivabradine 5 mg morning and evening for the first period of treatment during 8 days (1 capsule on day 1 and then 1 capsule 2 times a day from day 2 to day 7 and 1 capsule on day 8). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ivabradine | Drug | It is a cross over study with two arms : either ivabradine-placebo or placebo-ivabradine. The capsules containing the placebo or ivabradine are completely identical. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in viscosity of the common carotid artery | 8 days after first administration of ivabradine or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in diameter of the common carotid artery | 8 days after first administration of ivabradine or placebo | |
| Change from baseline in intima-media thickness of the common carotid artery | 8 days after first administration of ivabradine or placebo |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frederic Roca, MD | University Hospital, Rouen | Principal Investigator |
| Robinson Joannides, MD,PhD | University Hospital, Rouen | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Pharmacology, Rouen university Hospital | Rouen | 76000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10421594 | Background | Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study. Circulation. 1999 Jul 27;100(4):354-60. doi: 10.1161/01.cir.100.4.354. | |
| 17000623 | Background | Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588-605. doi: 10.1093/eurheartj/ehl254. Epub 2006 Sep 25. |
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| ID | Term |
|---|---|
| D000077550 | Ivabradine |
| D007785 | Lactose |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| lactose capsule (placebo) | Drug | It is a cross over study with two arms : either ivabradine-placebo or placebo-ivabradine. The capsules containing the placebo or ivabradine are completely identical. |
|
| Change from baseline in carotid distensibility | 8 days after first administration of ivabradine or placebo |
| Change from baseline in carotid-femoral pulse wave velocity | 8 days after first administration of ivabradine or placebo |
| Change from baseline in plasma levels of biomarkers of endothelial function | 8 days after first administration of ivabradine or placebo |
| Change from baseline in peripheral and central pressures | 8 days after first administration of ivabradine or placebo |
| Change from baseline in Buckberg index | 8 days after first administration of ivabradine or placebo |
| Change from baseline in cardiac output | 8 days after first administration of ivabradine or placebo |
| 9931080 | Background | Benetos A, Rudnichi A, Thomas F, Safar M, Guize L. Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure. Hypertension. 1999 Jan;33(1):44-52. doi: 10.1161/01.hyp.33.1.44. |
| 12052846 | Background | Lantelme P, Mestre C, Lievre M, Gressard A, Milon H. Heart rate: an important confounder of pulse wave velocity assessment. Hypertension. 2002 Jun;39(6):1083-7. doi: 10.1161/01.hyp.0000019132.41066.95. |
| 22412088 | Background | Bellien J, Iacob M, Remy-Jouet I, Lucas D, Monteil C, Gutierrez L, Vendeville C, Dreano Y, Mercier A, Thuillez C, Joannides R. Epoxyeicosatrienoic acids contribute with altered nitric oxide and endothelin-1 pathways to conduit artery endothelial dysfunction in essential hypertension. Circulation. 2012 Mar 13;125(10):1266-75. doi: 10.1161/CIRCULATIONAHA.111.070680. |
| 18757088 | Background | Fox K, Ford I, Steg PG, Tendera M, Ferrari R; BEAUTIFUL Investigators. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Sep 6;372(9641):807-16. doi: 10.1016/S0140-6736(08)61170-8. Epub 2008 Aug 29. |
| 23090775 | Background | Bellien J, Remy-Jouet I, Iacob M, Blot E, Mercier A, Lucas D, Dreano Y, Gutierrez L, Donnadieu N, Thuillez C, Joannides R. Impaired role of epoxyeicosatrienoic acids in the regulation of basal conduit artery diameter during essential hypertension. Hypertension. 2012 Dec;60(6):1415-21. doi: 10.1161/HYPERTENSIONAHA.112.201087. Epub 2012 Oct 22. |
| 23933545 | Background | Reil JC, Tardif JC, Ford I, Lloyd SM, O'Meara E, Komajda M, Borer JS, Tavazzi L, Swedberg K, Bohm M. Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients. J Am Coll Cardiol. 2013 Nov 19;62(21):1977-1985. doi: 10.1016/j.jacc.2013.07.027. Epub 2013 Aug 7. |
| 16433867 | Background | Joannides R, Moore N, Iacob M, Compagnon P, Lerebours G, Menard JF, Thuillez C. Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise. Br J Clin Pharmacol. 2006 Feb;61(2):127-37. doi: 10.1111/j.1365-2125.2005.02544.x. |
| 24275838 | Background | Boutouyrie P, Beaussier H, Achouba A, Laurent S; EXPLOR trialists. Destiffening effect of valsartan and atenolol: influence of heart rate and blood pressure. J Hypertens. 2014 Jan;32(1):108-14. doi: 10.1097/HJH.0000000000000014. |
| 16702490 | Background | Tropeano AI, Boutouyrie P, Pannier B, Joannides R, Balkestein E, Katsahian S, Laloux B, Thuillez C, Struijker-Boudier H, Laurent S. Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension. 2006 Jul;48(1):80-6. doi: 10.1161/01.HYP.0000224283.76347.8c. Epub 2006 May 15. |
| 25176136 | Background | Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R; SIGNIFY Investigators. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014 Sep 18;371(12):1091-9. doi: 10.1056/NEJMoa1406430. Epub 2014 Aug 31. |
| 18414390 | Background | Drouin A, Gendron ME, Thorin E, Gillis MA, Mahlberg-Gaudin F, Tardif JC. Chronic heart rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice. Br J Pharmacol. 2008 Jun;154(4):749-57. doi: 10.1038/bjp.2008.116. Epub 2008 Apr 14. |
| 16476843 | Background | Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O'Rourke M; CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006 Mar 7;113(9):1213-25. doi: 10.1161/CIRCULATIONAHA.105.595496. Epub 2006 Feb 13. |
| 21926346 | Background | Bolduc V, Drouin A, Gillis MA, Duquette N, Thorin-Trescases N, Frayne-Robillard I, Des Rosiers C, Tardif JC, Thorin E. Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2081-92. doi: 10.1152/ajpheart.00706.2011. Epub 2011 Sep 16. |
| 20452592 | Background | Maltete D, Bellien J, Cabrejo L, Iacob M, Proust F, Mihout B, Thuillez C, Guegan-Massardier E, Joannides R. Hypertrophic remodeling and increased arterial stiffness in patients with intracranial aneurysms. Atherosclerosis. 2010 Aug;211(2):486-91. doi: 10.1016/j.atherosclerosis.2010.04.002. Epub 2010 Apr 13. |
| 37532594 | Result | Roca F, Zmuda L, Noel G, Duflot T, Iacob M, Moreau-Grange L, Prevost G, Joannides R, Bellien J. Changes in carotid arterial wall viscosity and carotid arterial stiffness in type 2 diabetes patients. Atherosclerosis. 2024 Jul;394:117188. doi: 10.1016/j.atherosclerosis.2023.117188. Epub 2023 Jul 6. |
| 35112890 | Result | Roca F, Iacob M, Duflot T, Donnadieu N, Thill C, Bellien J, Joannides R. Adaptation of Arterial Wall Viscosity to the Short-Term Reduction of Heart Rate: Impact of Aging. J Am Heart Assoc. 2022 Feb 15;11(4):e023409. doi: 10.1161/JAHA.121.023409. Epub 2022 Feb 3. |
| D004187 | Disaccharides |
| D009844 | Oligosaccharides |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D000073893 | Sugars |