Heart Rate Reduction Via Oral Ivabradine During Exercise in Healthy Adults to Understand Heart Rate/Work-rate Relations: A Pilot Dose-selection Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Heart rate, peak
研究概览
简要总结
During exercise, working muscles require more oxygen. The heart meets this demand in two ways: by beating faster (heart rate) and by pumping more blood with each beat (stroke volume). Heart rate increases steadily with exercise intensity until exhaustion, but the amount of blood pumped with each beat tends to plateau at moderate intensities. Why the amount of blood pumped with each beat becomes limited before heart rate, however, is not well understood.
Studying these mechanisms is difficult because most drugs that lower heart rate also affect how strongly the heart pumps, making it hard to separate the two effects. One medication that can help with this is ivabradine, which is used to treat people with heart disease who have high resting heart rates. It slows the heart rate without changing how strongly the heart pumps.
This study will investigate whether ivabradine lowers heart rate during exercise in healthy younger and older adults, and whether a higher dose lowers heart rate more. The results will help us better understand how heart rate influences the heart's ability to supply oxygen to the body during exercise, and what limits the ability to exercise as people age.
Participants will:
- Attend three visits at SportsCardiologyBC in Vancouver
- Complete a cycling exercise test at each visit to measure heart rate and how hard they can exercise
- Take ivabradine (a heart-rate-lowering medication) before the exercise test at Visits 2 and 3 (a lower dose at Visit 2 and a higher dose at Visit 3)
- Be monitored for side effects including slow heart rate, visual symptoms, and headache.
详细描述
Heart rate and stroke volume are generally considered as two independent factors which influence cardiac output, yet they are interlinked by cellular (e.g., calcium handling) and hemodynamic (e.g., diastolic pressure decay) mechanisms. Delineating how heart rate and stroke volume influence cardiac output and exercise capacity, even within healthy individuals, has historically been experimentally difficult as pharmacologic perturbations, such as beta-adrenergic antagonists, influence both heart rate and heart muscle performance. Ivabradine selectively reduces heart rate in a dose-dependent manner, without impacting myocardial contractility, cardiac afterload, or venous return. However, it has largely been studied in clinical outcome trials in adults with heart failure, or safety studies in younger healthy adults. As such, there is a knowledge gap on how ivabradine influences heart rate and exercise capacity in healthy younger and older adults.
Study Purpose To characterize the effects of two single doses of ivabradine (7.5 mg and 12.5 mg) on heart rate during incremental exercise in younger and older healthy adults.
Exploratory Aim To assess the safety and tolerability of two single doses of ivabradine (7.5 mg and 12.5 mg) in younger and older healthy adults.
Hypothesis Ivabradine will produce dose-dependent reductions in peak exercise heart rate and heart rate/work-rate relationships (anticipated to be approximately 10-15%, on average).
Research Design Unblinded, non-randomized, repeated measures design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males and females aged 19-39 years, and 60-79 years
- •Engaging in regular aerobic exercise (e.g., running, cycling, swimming, hiking, field, ice, or racquet sports) at least once per week
排除标准
- •History of any cardiovascular condition, including hypertension
- •Use of any chronic medication
- •History of any respiratory condition, including asthma
- •Smoking, including cannabis or vaping in the past year
- •History of diabetes mellitus, cancer, hepatic, renal or any other chronic illness
- •Seated blood pressure ≥130/90 or <100/60 mmHg
- •Body mass index <20 or >32 kg/m2
- •Non-sinus rhythm or abnormalities on 12-lead electrocardiogram (ECG)
- •Pregnant, breastfeeding, or women of childbearing potential not using appropriate contraception
- •Current or recent (past year) participation in >150 minutes per week of moderate-vigorous intensity exercise (to avoid endurance training-related bradycardia)
- •Any condition that prevents vigorous exercise from being performed safely
- •Seated resting heart rate <60 beats per minute
- •Prolonged QT interval (e.g., long QT syndrome)
- •Sick sinus syndrome, sino-atrial block or third-degree atrio-ventricular block
- •Use of strong cytochrome P450 (CYP3A4) inhibitors (e.g., nirmatrelvir and ritonavir, ketoconazole), which can increase ivabradine levels in the blood to potentially unsafe levels
- •Use of verapamil or diltiazem, which are moderate CYP3A4 inhibitors and also lower heart rate, posing a risk of excessive bradycardia when combined with ivabradine
- •Lactose intolerance, as ivabradine contains lactose
- •Known allergy/hypersensitivity to ivabradine or to any ingredient in the formulation or component of the container
研究组 & 干预措施
Ivabradine
All participants receive two single oral doses of ivabradine in a fixed sequence across separate experimental visits.
干预措施: Ivabradine (single oral dose) (Drug)
结局指标
主要结局
Heart rate, peak
时间窗: Within 30 minutes of exercise onset
Highest heart rate achieved during the cardiopulmonary exercise test.
次要结局
- Incidence of headache(Within 4 hours post-dose administration)
- Incidence of bradycardia(Within 4 hours post-dose administration)
- Heart rate, resting(Within 15 minutes prior to exercise onset)
- Heart rate/work rate(Within 30 minutes of exercise onset)
- Incidence of visual symptoms(Within 4 hours post-dose administration)
研究者
Nathaniel Moulson
Clinical Assistant Professor, Department of Medicine
University of British Columbia