Clinical trial NCT02584439: Effect of Pharmacological Heart Rate Reduction on Visco-elastic Properties of the Arterial Wall (BRADYVASC)
Official title: Effect of Pharmacological Heart Rate Reduction on Visco-elastic Properties of the Arterial Wall (BRADYVASC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Healthy
Vascular Stiffness
Aging
Keywords: ivabradine
heart rate
aging
visco-elasticity
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2015-10-22
Enrollment: 30
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Healthy volunteers
* Caucasian
* Resting heart rate ≥70 bpm (mean of 3 measures after 15 minutes of rest)
* No significant EKG abnormality
* No significant biological abnormalities at inclusion
* 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)

Exclusion Criteria:

* 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)
* Active smoking at the day of inclusion (\>5 cigarettes/day)
* 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
* High-grade conduction block (Sick sinus syndrome, sino-atrial block or grade 2 or 3 atrio-ventricular block)
* Abnormal corrected QT with Bazett formula (cQT \> 450 ms (men) or \> 470 ms (women)).
* Pacemaker
* All cardiac or extra cardiac diseases, active or with sequelae, which, in the opinion of the investigator, is accompanied by a risk of cardiac or vascular consequences
* Retinal disease
* Taking any medication is prohibited during the study except oral contraceptive, acetaminophene or decision of the investigator. In addition, the administration of drugs listed in schedule 2 during the previous 4 weeks prohibits inclusion.

Primary outcomes:
measure: Change from baseline in viscosity of the common carotid artery
timeFrame: 8 days after first administration of ivabradine or placebo
Secondary outcomes:
measure: Change from baseline in diameter of the common carotid artery
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in intima-media thickness of the common carotid artery
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in carotid distensibility
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in carotid-femoral pulse wave velocity
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in plasma levels of biomarkers of endothelial function
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in peripheral and central pressures
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in Buckberg index
timeFrame: 8 days after first administration of ivabradine or placebo
measure: Change from baseline in cardiac output
timeFrame: 8 days after first administration of ivabradine or placebo
Other outcomes:
Locations:
city: Rouen
country: France
facility: Department of Pharmacology, Rouen university Hospital
Study officials:
affiliation: University Hospital, Rouen
name: Frederic Roca, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Rouen
name: Robinson Joannides, MD,PhD
role: STUDY_CHAIR
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