Effect of Pharmacological Heart Rate Reduction on Visco-elastic Properties of the Arterial Wall (BRADYVASC)

NCT02584439 | Completed Phase 3 DMC

• 2 other identifiers: 2015/077/HP2015-002060-17
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy; Vascular Stiffness; Aging

Keywords

ivabradine; heart rate; aging; visco-elasticity

Outcome Measures

Primary Outcomes (1)

• Change from baseline in viscosity of the common carotid artery

  8 days after first administration of ivabradine or placebo

Secondary Outcomes (8)

• 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

• 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

Study Arms (2)

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).

Drug: ivabradine; Drug: lactose capsule (placebo)

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).

Drug: ivabradine; Drug: lactose capsule (placebo)

Interventions

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.

ivabradine-placebo; placebo-ivabradine

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.

Also known as: Procoralan

ivabradine-placebo; placebo-ivabradine

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers
• Caucasian
• Resting heart rate ≥70 bpm (mean of 3 measures after 15 minutes of rest)
• No significant EKG abnormality
• Healthy volunteers able to read and understand information letter and to give written informed consent
• Healthy volunteers with medical insurance
• Contraception for two months for women of childbearing age (Estrogen contraceptive or intrauterine device or tubal ligation) (NB : women with amenorrhea for more than 2 years will be considered postmenopausal)

You may not qualify if:

• Subjects who don't understand french language
• Person deprived of liberty by an administrative or judicial decision or protected adult subject (under guardianship)
• Pregnant women, nursing mother or women without contraception
• Healthy volunteers who participate to an other trial / participated to an other trial without drugs during the last month or a trial with drugs during the last 3 months
• Hypersensitivity to the active substance or to any of the excipients
• Congenital galactosemia, lactase deficiency, or glucose-galactose malabsorption
• Body mass index (BMI) \< 18 kg/m² or \> 30 kg/m²
• Severe hypotension (\< 90/50 mmHg) (3 measures after 15 minutes of rest)
• Essential or secondary Hypertension (SBP ≥140 mmHg and/or DBP ≥90 mmHg) (3 measures after 15 minutes of rest)
• Severe hypercholesterolemia (Total cholesterol \>2,5 g/L)
• Practice sports intensively (≥ 1 hour/day)
• Renal insufficiency (creatinine clearance ≤ 60 ml/min/1,73 m² Cockroft and Gault formula)
• Known liver failure
• Known heart failure or suspected heart failure (congestive episode)
• Atrial fibrillation

Sponsors & Collaborators

• University Hospital, Rouen: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Department of Pharmacology, Rouen university Hospital

Rouen, 76000, France

Location

Related Publications (18)

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

  PMID: 37532594 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.

  PMID: 35112890 RESULT

MeSH Terms

Interventions

Ivabradine; Lactose

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Frederic Roca, MD

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

• Robinson Joannides, MD,PhD

  University Hospital, Rouen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 22, 2015
• Study Start: December 3, 2015
• Primary Completion: July 15, 2019
• Study Completion: July 15, 2019
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

FR (1)