CO2 Rebreathing to Increase Blood Pressure in Neurogenic Orthostatic Hypotension: A Proof-of-Concept Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Δ Blood Pressure (BP)
研究概览
简要总结
Neurogenic orthostatic hypotension (nOH) is a chronic condition associated with increased cardiovascular risk and reduced quality of life. On standing, patients with nOH experience a large reduction in blood pressure (BP; at least ≥20/10mmHg, but often much more), which is often accompanied by debilitating symptoms and syncope. A previous study (unpublished) showed that hypercapnia significantly increases standing BP in patients with nOH. Human bodies naturally produce and exhale CO2. Rebreathe devices offer a simple, cost-effective technology to increase arterial CO2. In brief, rebreathe devices work by capturing expired CO2, which is then re-inhaled. The net effect is a transient increase in CO2. A CO2 rebreathing device may offer a novel hemodynamic therapy for patients with nOH.
This is a pilot, proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH. The hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH.
Male and female patients (n=28) will be asked to complete two randomized 70° head-up tilt (HUT) tests breathing either room air or using a CO2 rebreather. Hemodynamics (BP, heart rate, stroke volume, brain blood flow) and orthostatic symptoms will be assessed throughout. Breath-by-breath data will include O2, CO2, respiration rate and tidal volume.
The primary outcome measure will be the magnitude of the BP response (ΔBP = HUT - Supine) during Room Air vs. Hypercapnia. The primary outcome will be compared between room air and hypercapnia using a paired t-test.
详细描述
BACKGROUND: Neurogenic orthostatic hypotension (nOH) is a chronic condition associated with increased cardiovascular risk and reduced quality of life. On standing, patients with nOH experience a large reduction in blood pressure (BP; at least ≥20/10mmHg, but often much more), which is often accompanied by debilitating symptoms and syncope. nOH affects the elderly and patients with neurodegenerative diseases (e.g., Parkinson's disease, multiple system atrophy), neuropathies (e.g., diabetes), and neural injury (e.g., spinal cord injury).
In healthy controls, hypercapnia (i.e., high CO2) increases in sympathetic nerve activity and BP. Hypercapnia significantly increases supine and seated BP in patients with nOH, and a previous study (unpublished) showed that hypercapnia significantly increases standing BP in patients with nOH.
Human bodies naturally produce and exhale CO2. Rebreathe devices offer a simple, cost-effective technology to increase arterial CO2. In brief, rebreathe devices work by capturing expired CO2, which is then re-inhaled. The net effect is a transient increase in CO2. A CO2 rebreathing device may offer a novel hemodynamic therapy for patients with nOH.
OBJECTIVE: This is a pilot, proof-of-concept study to evaluate a CO2 rebreather to improve blood pressure and orthostatic tolerance in patients with nOH. The study hypothesis is that a rebreather will increase CO2 sufficiently enough to improve BP in patients with nOH.
METHODS: Male and female patients (n=28) will be recruited from the Calgary Autonomic Investigation and Management Clinic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Male and Female
- •Physician diagnosis of Neurogenic Orthostatic Hypotension
- •Non-smokers.
- •Able and willing to provide informed consent.
- •Ability to travel to Libin Cardiovascular Institute Autonomic Testing Lab at the University of Calgary, Calgary, AB.
排除标准
- •Medical therapies or medications which could interfere with testing of autonomic function
- •Pregnant or breast-feeding females
- •Subjects with chronic heart failure or severe pulmonary disease who are unable to climb one flight of stairs due to shortness of breath.
- •Presence of failure of other organ systems or systemic illness that can affect autonomic function or the participant's ability to cooperate. These include dementia, alcohol and/or drug abuse, cerebrovascular disease, kidney or liver disease, surgical procedures where the nerves of the sympathetic nervous system have been cut.
- •Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies.
研究组 & 干预措施
CO2 Rebreathing
Participants will breathe with the rebreather in the supine position until CO2 levels increase between 5-10mmHg. Once CO2 levels are increased, participants will be tilted upright, and will continue to breathe with the rebreather during a 5-min HUT test
干预措施: CO2 ReHaler (Device)
Room Air
Participants will breathe room air in the supine position and during a 5-min HUT test
结局指标
主要结局
Δ Blood Pressure (BP)
时间窗: The ΔBP (HUT-Supine) calculated as the average BP in the final two minutes of supine baseline and the average BP between minute 3 and 5 of HUT will be compared between room air and CO2 rebreathe
Magnitude of ΔBP (HUT-Supine) breathing room air vs CO2 rebreathe
次要结局
- Δ Vanderbilt Orthostatic Symptom Score [Range: 0 (absent) to 10 (worst)](The Δ Vanderbilt Orthostatic Symptom Score (symptoms at the 5th minute of HUT - symptoms at the 5th minute of supine rest) will be compared between room air vs CO2 rebreathe)
- Δ Cerebral Blood Flow Velocity (CBFv)(The ΔCBFv (HUT-Supine) calculated as the average CBFv in the final two minutes of supine baseline and the average CBFv between minute 3 and 5 of HUT will be compared between room air and CO2 rebreathe)
研究者
Dr. Satish Raj
Professor
University of Calgary