The Effects of Exercise Training on Central and Peripheral Blood Flow Regulation in Individuals With Down Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change From Baseline Work Capacity at 13 Weeks
研究概览
简要总结
Work capacity is an important predictor of declining health or physical function, and of mortality, and is commonly measured as peak oxygen consumption. Peak oxygen consumption is very low in individuals with Down syndrome, the most prevalent genetic cause of intellectual disability. Previous research suggests individuals with Down syndrome may experience a double disadvantage when they are exercising: they may not be able to increase cardiac output sufficiently and they may not be able to allocate adequate blood flow to the working muscles. The aim of this research proposal is therefore to investigate the responses in central and peripheral blood flow regulation and cardiac autonomic function to exercise training in individuals with DS. Additionally the effects of exercise on gait, balance and attitude towards exercise in individuals with DS are investigated.
详细描述
Down syndrome (DS) is the most prevalent genetic cause of intellectual disability and occurs in approximately 1 in every 700 births in the US. Individuals with DS are at increased risk for a number of health issues. Work capacity is an important predictor of declining health or physical function, and of mortality, and is commonly measured as peak oxygen consumption. Peak oxygen consumption is very low in individuals with DS, and cannot be explained by physical inactivity, lack of motivation, or lack of understanding of the test. To date, the nature of the limitations in work capacity in DS is unknown, and the proposed research aims to address this knowledge gap.
Work capacity is determined by central and peripheral regulation of blood flow (i.e. cardiac output and maintaining arterial blood pressure vs. supplying exercising muscles with oxygen and nutrients). These factors are governed by the sympathetic and parasympathetic branches of the autonomic nervous system. Central regulation of blood flow is impaired in individuals with DS due to cardiovascular autonomic dysfunction, whereby parasympathetic activity is high and sympathetic control is reduced. This results in lower heart rate, less adequate blood pressure control and attenuated catecholamine levels during exercise. It is unknown to what extent this impaired central control impacts cardiac output, and subsequently work capacity, during exercise in individuals with DS.
Peripheral blood flow regulation is even less studied in individuals with DS. Peripheral regulation involves sympathetically regulated vasoconstriction in non-active muscles and tissues, and local mechanisms regulating vasodilation in working muscles, which facilitates blood flow to working muscle in order to meet metabolic demand. Individuals with DS may partly experience reduced work capacity due to this inability to shunt blood to the working tissue effectively. Our pilot data supports this hypothesis in that individuals with DS are unable to vasoconstrict in response to lower body negative pressure, a known sympathoexcitatory maneuver that produces vasoconstriction in controls without disabilities. Importantly, the impact of their lack of sympathetically mediated vasoconstriction on exercise has not been studied, and neither have the local mechanisms regulating appropriate vasodilation in working muscles.
The aim of this research proposal is therefore to determine the impact of limitations in central and peripheral regulation of blood flow on work capacity in individuals with DS. The aim is to examine the responses to exercise training to better understand the underlying mechanisms and the potential to improve health by using this knowledge in exercise interventions.
Overall Aim: To investigate the responses in central and peripheral blood flow regulation and cardiac autonomic function to exercise training in individuals with DS Aim 1: To determine if exercise training improves peripheral or central regulation of blood flow in individuals with DS. The investigators hypothesize that improvements in work capacity in response to chronic exercise training are primarily due to improvements in peripheral blood flow regulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
盲法说明
As this is an exercise intervention, both the study team and the participant will be aware of which group the participant is assigned to.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •generally healthy
- •sedentary (defined as being involved in less than 30 minutes of moderately-intense physical activity per day)
- •additionally for the participants with Down syndrome:
- •diagnosis of Down syndrome trisomy 21 and
- •normal thyroid function or stable thyroid function (and medications) for at least 6 mo.
排除标准
- •congenital heart disease;
- •atherosclerotic or other vascular disease;
- •asthma or other pulmonary disease;
- •hypertension (defined BP >140/90 mmHg);
- •blood pressure below 90/60 mmHg;
- •history of pre-syncope or syncope;
- •diabetes (defined as Hba1c of >7.5% or use of glucose lowering medication);
- •severe obesity (defined as BMI >40);
- •medications affecting heart rate, blood pressure or arterial function;
- •anti-inflammatory medication including NSAIDS;
- •current smoking and
- •pregnancy.
研究组 & 干预措施
Combined exercise intervention Down syndrome
The exercise intervention will last 12 weeks and will consist of a supervised combined aerobic and resistance training program with a frequency of 3 days/week.In the exercise sessions, the participant will work with the trainer on their strength, balance and aerobic endurance. Each session consists of 10 min of strength exercises (Foundational Exercise), 10 min of Hip Strengthening, 10 min of Vestibular and Balance Exercise, and 20 min of Aerobic Exercise, and starts with a warming up and ends with stretching/cooling down. Each new exercise will be introduced in easy steps and practiced until the participant is comfortable executing it.
干预措施: Combined exercise intervention (Behavioral)
Usual care Down Syndrome
The control condition consists of usual activities.
干预措施: Usual care / Sham intervention (Behavioral)
Reference group without Down syndrome
This reference group of age- and sex-matched inactive individuals without Down syndrome will undergo the same baseline testing as the other groups but without intervention or post-intervention measures.
结局指标
主要结局
Change From Baseline Work Capacity at 13 Weeks
时间窗: 13 weeks
Change in work capacity from baseline to 13 weeks, as measured by peak oxygen uptake in ml/kg/min with a graded exercise test on a treadmill.
次要结局
- Change From Baseline Brachial Blood Flow at 13 Weeks(13 weeks)
- Change From Baseline Muscle Oxygenation at 13 Weeks(13 weeks)
- Change From Baseline Cardiac Output (Aortic Blood Flow) at 13 Weeks(13 weeks)
- Change From Baseline Autonomic Cardiac Function at Rest at 13 Weeks(13 weeks)
- Change From Baseline Autonomic Cardiac Function During Orthostasis at 13 Weeks(13 weeks)
- Change From Baseline IL-6 at 13 Weeks(13 weeks)
- Change From Baseline HDL at 13 Weeks(13 weeks)
- Change From Baseline Superoxide Dismutase at 13 Weeks(13 weeks)
- Change From Baseline Comfortable Walking Speed at 13 Weeks(13 weeks)
- Change From Baseline Fast Walking Speed at 13 Weeks(13 weeks)
- Change From Baseline Functional Reach at 13 Weeks(13 weeks)
- Change From Baseline Timed Up and Go at 13 Weeks(13 weeks)
- Change From Baseline Standing Balance at 13 Weeks(13 weeks)