Sleep and Circadian Mechanisms in Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Heart rate variability (Circadian and Overnight sleep vs. rested wakefulness trial)
研究概览
简要总结
This study is a mechanistic clinical trial designed to investigate the effects of the circadian system and sleep on non-dipping blood pressure (BP) in people with hypertension (HTN).
详细描述
This study is a mechanistic clinical trial designed to study the effects of the circadian system and sleep on non-dipping blood pressure (BP) in people with hypertension (HTN). Investigators will study participants with dipping and non-dipping hypertension. All participants will partake in all experiments. First, investigators will assess sleep in the participants' home environment using unattended polysomnography. Participants will then complete a 5-day overnight forced desynchrony laboratory protocol to uncover circadian rhythms (Constant Routine). The second experiment is a randomized crossover protocol. Two trials (Overnight Sleep and Rested Wakefulness) will be completed in randomized order to separate the effects of sleep on non-dipping blood pressure while assessing nighttime cardiovascular mechanisms. Finally, investigators will pilot test if 2 weeks of sleep regularization impacts 24-hour BP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 25-64
- •BMI 18.5-42kg/m2
- •Hypertension (average resting blood pressure between 130/80 mmHg and 160/100 mmHg)
排除标准
- •Over 5 pack-years of smoking;
- •Prior shift work within 12 months prior to the study;
- •Travel greater than three time zones for at least 3 months;
- •History of heart failure, cardiomyopathy, or history of bypass surgery, angioplasty, or previous myocardial infarction;
- •Acute or chronic diseases (except hypertension) that may affect outcome measures;
- •History of psychological conditions;
- •Sleep disorders, like severe sleep apnea, insomnia, etc.;
- •Prescription medications (Contraceptives and anti-hypertensive medications are permissible);
- •History of Illicit drug use and alcohol dependency;
- •30 days free of cannabis use prior to the study;
- •Pregnancy;
- •Upper cut-off of 160/100 mmHg for BP
研究组 & 干预措施
Dipping vs non-dipping HTN
Participants will wear an ambulatory blood pressure monitor (SpaceLabs, Inc.) which will take their blood pressure in 20-30-minute intervals for 24-48 hours to determine blood pressure dipping status.
All participants in this arm will complete the experiments in this order:
- At-home polysomnography;
- Constant Routine protocol;
- Rested Wakefulness Trial AND Overnight Sleep Trial (Randomized crossover);
- Sleep Regularization Trial
干预措施: At-home Polysomnography (Other)
Dipping vs non-dipping HTN
Participants will wear an ambulatory blood pressure monitor (SpaceLabs, Inc.) which will take their blood pressure in 20-30-minute intervals for 24-48 hours to determine blood pressure dipping status.
All participants in this arm will complete the experiments in this order:
- At-home polysomnography;
- Constant Routine protocol;
- Rested Wakefulness Trial AND Overnight Sleep Trial (Randomized crossover);
- Sleep Regularization Trial
干预措施: Circadian Protocol (Other)
Dipping vs non-dipping HTN
Participants will wear an ambulatory blood pressure monitor (SpaceLabs, Inc.) which will take their blood pressure in 20-30-minute intervals for 24-48 hours to determine blood pressure dipping status.
All participants in this arm will complete the experiments in this order:
- At-home polysomnography;
- Constant Routine protocol;
- Rested Wakefulness Trial AND Overnight Sleep Trial (Randomized crossover);
- Sleep Regularization Trial
干预措施: Rested Wakefulness Trial (Other)
Dipping vs non-dipping HTN
Participants will wear an ambulatory blood pressure monitor (SpaceLabs, Inc.) which will take their blood pressure in 20-30-minute intervals for 24-48 hours to determine blood pressure dipping status.
All participants in this arm will complete the experiments in this order:
- At-home polysomnography;
- Constant Routine protocol;
- Rested Wakefulness Trial AND Overnight Sleep Trial (Randomized crossover);
- Sleep Regularization Trial
干预措施: Overnight Sleep Trial (Other)
Dipping vs non-dipping HTN
Participants will wear an ambulatory blood pressure monitor (SpaceLabs, Inc.) which will take their blood pressure in 20-30-minute intervals for 24-48 hours to determine blood pressure dipping status.
All participants in this arm will complete the experiments in this order:
- At-home polysomnography;
- Constant Routine protocol;
- Rested Wakefulness Trial AND Overnight Sleep Trial (Randomized crossover);
- Sleep Regularization Trial
干预措施: Regularized Sleep Schedule (Behavioral)
结局指标
主要结局
Heart rate variability (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
For the duration of all in-laboratory studies, three channels of EKG are recorded (RA-V6) and stored at a sampling frequency of 256 Hz. This software will be used for peak detection (R-wave detection and subsequent heart rate variability (HRV) analysis to estimate cardiac vagal tone). Investigators will study circadian rhythms in heart rate between people with dipping vs non-dipping hypertension. Investigators will also study how overnight sleep affects heart rate variability in these groups. This is a measure of cardiac parasympathetic activity and cardiovascular health.
Norepinephrine (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Plasma norepinephrine (measured in plasma according to laboratory values) will be measured to estimate sympathetic output (stress). Higher values may indicate increased cardiovascular risk. Investigators will study circadian rhythms in Norepinephrine between people with dipping vs non-dipping hypertension. Investigators will also study how overnight sleep affects Norepinephrine in these groups.
Sleep Episodes (At-home Polysomnography)
时间窗: 1-2 nights
Sleep episodes will be polysomnographically recorded and scored in 30-sec epochs for sleep stage, arousals, and respiratory events on SomnoMedics Domino Software. Values (based on software analysis) provide a description of what aspects of sleep are different between participants.
Sleep duration (At-home Polysomnography)
时间窗: 1-2 nights
Sleep duration will be scored from the ActiGraph and correlated with the sleep and activity diary. Sleep duration measures the amount of time asleep (in minutes).
Muscle sympathetic nerve activity (MSNA) (Overnight sleep vs. rested wakefulness trial and circadian trial)
时间窗: 7 days
MSNA may be directly measured by inserting a tungsten microelectrode (Frederick Haer, Bowdoinham, ME) into a peroneal nerve at the popliteal fossa. A reference electrode will be inserted subcutaneously 2-3 cm from the recording electrode. Both electrodes will be connected to a differential preamplifier and then to an amplifier to obtain mean voltage neurograms. Once investigators have confirmed a satisfactory post-ganglionic MSNA recording, the participants will be provided a 10 min non-recorded rest to ensure baseline levels. Data will be recorded using WinDaq/Pro data acquisition software (DATAQ Instruments, Akron, OH) and imported for analysis in the commercially available WinCPRS software program (Absolute Aliens; Turku, Finland). Investigators will also study how overnight sleep affects MSNA in these groups. Investigators may also study circadian rhythms in MSNA between people with dipping vs non-dipping hypertension.
Vascular endothelial function (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Investigators will measure endothelial function as flow-mediated dilation (FMD). Investigators will measure brachial artery FMD using standard procedures every 3 hours in the constant routine protocol and while awake during the overnight sleep vs. rested wakefulness trial. Investigators will also normalize FMD to the hyperemic shear. Investigators will study circadian rhythms in vascular function in people with dipping vs non-dipping hypertension. Investigators will also study if overnight sleep changes morning vascular function between these groups. Vascular function may be an indicator of cardiovascular health.
Magnitude of overnight blood pressure dipping (Overnight sleep vs. rested wakefulness trial)
时间窗: 2 days
Blood Pressure (BP) dipping will be calculated as the percent reduction in average nighttime BP reduction compared to daytime BP. Both systolic and diastolic blood pressure will be measured in mmHg. Blood pressure dipping status may be an indicator of cardiovascular health. Investigators will study whether being asleep or not changes the magnitude of dipping between dipping and non-dipping hypertension. Investigators will also measure ancillary variables such as average daytime BP, night time BP, and morning surge in BP.
Blood pressure (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Blood pressure (BP; systolic and diastolic) will be measured in a supine or semi-recumbent position. Investigators will measure beat-by-beat BP using a noninvasive device employing the volume-clamp method with hydrostatic correction. Investigators will measure BP using a calibrated sphygmomanometer to record sporadic BP at regular intervals throughout the protocols. Investigators will study circadian rhythms in blood pressure between people with dipping vs non-dipping hypertension. Investigators will also study how overnight sleep affects blood pressure in these groups. Investigators will also study ancillary variables such as morning surge in blood pressure. All blood pressure measurements will be measured in mmHg.
Heart rate (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Heart rate will be measured in beats-per-minute (bpm). This is a standard marker of cardiovascular health.
Epinephrine (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Plasma epinephrine (measured in plasma according to laboratory values) will be measured to estimate sympathetic output (stress). Higher values may indicate increased cardiovascular risk. Investigators will study circadian rhythms in Epinephrine between people with dipping vs non-dipping hypertension. Investigators will also study how overnight sleep affects Epinephrine in these groups.
Aldosterone (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Plasma aldosterone (measured in plasma according to laboratory values) will be measured to estimate sympathetic output (stress). Higher values may indicate increased cardiovascular risk. Investigators will study circadian rhythms in Aldosterone between people with dipping vs non-dipping hypertension. Investigators will also study how overnight sleep affects Aldosterone in these groups.
Renin (Circadian and Overnight sleep vs. rested wakefulness trial)
时间窗: 7 days
Plasma renin/activity (measured in plasma according to laboratory values) will be measured to estimate sympathetic output (stress). Higher values may indicate increased cardiovascular risk. Investigators will also study circadian rhythms in renin between people with dipping vs non-dipping hypertension. Investigators will also study how overnight sleep affects renin in these groups.
次要结局
- Blood pressure dipping status (Sleep regularization trial)(2 weeks)
- Ambulatory blood pressure (Sleep regularization trial)(2 weeks)
研究者
Saurabh Thosar
Assistant Professor
Oregon Health and Science University