Diffuse Optical Monitoring With Inhaled Nitric Oxide

Study Overview
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Brief Summary
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This study is a non-randomized, Phase 2 clinical trial designed to measure the cerebral blood flow (CBF) response to inhaled nitric oxide in acute ischemic stroke patients and healthy subjects. The monitoring is a 35 minute session during which cerebral hemodynamics will be monitored with both diffuse correlation spectroscopy (DCS) and transcranial doppler ultrasonography (TCD) while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide (NO)/nitrogen dioxide (NO2) concentration, are continuously monitored.

Official Title
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Diffuse Optical Monitoring With Inhaled Nitric Oxide

Conditions
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Stroke

Intervention / Treatment
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* Drug: Nitric Oxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stroke Patients: Age greater than 18 Acute ischemic stroke in the territory of the anterior, middle, or posterior cerebral artery, on either side of the brain Study can be initiated within 72 hours of stroke symptom onset 3. Ability and willingness to sign informed consent Healthy subjects: Age greater than 18 Ability and willingness to sign informed consent Exclusion Criteria: Stroke subjects: History of prior stroke or transient ischemic attack Known cerebrovascular abnormality History of congestive heart failure Presence of pneumonia or active pulmonary infection Current use of any NO donor medication (sodium nitroprusside or nitroglycerin) Age less than 18 years Skull defect that would interfere with CBF monitoring Pregnancy Structural brain lesion Prior neurosurgical procedure History of psychiatric disease Any medical condition that the clinical investigator feels would pose a hazard to the subject if he/she participated in the study Healthy subjects: History of any neurological disease History of stroke or transient ischemic attack Known cerebrovascular abnormality History of congestive heart failure History of chronic pulmonary disease such as asthma or chronic obstructive pulmonary disease Presence of pneumonia or active pulmonary infection Current use of any NO donor medication (sodium nitroprusside or nitroglycerin) Age less than 18 years Skull defect that would interfere with CBF monitoring Pregnancy (urine or blood tests will not be performed) Structural brain lesion Prior neurosurgical procedure History of psychiatric disease Any medical condition that the clinical investigator feels would pose a hazard to the subject if he/she participated in the study Cognitive impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Controls<br>The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be called at 24 hours after the monitoring session to determine any tolerability issues or adverse events. | Drug: Nitric Oxide<br>* Inhaled Nitric Oxide gas<br>* Other names: NO2;|
| Experimental: Acute Ischemic Stroke<br>Patients will be enrolled in the study within 72 hours of stroke symptom onset. The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be undergo a final assessment at 24 hours after the monitoring session to determine any tolerability issues or adverse events. | Drug: Nitric Oxide<br>* Inhaled Nitric Oxide gas<br>* Other names: NO2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cerebral blood flow during the administration of iNO |  | Conclusion of the 35 minute protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood flow velocity as measured by TCD during iNO administration |  | Conclusion of the 35 minute protocol | 
| Change in mean arterial blood pressure (MAP) during iNO administration |  | Conclusion of the 35 minute protocol | 
| Time to maximum CBF effect after the introduction of iNO |  | Conclusion of the 35 minute protocol | 
| Duration of residual effect after cessation of iNO (time to return to baseline) |  | Conclusion of the 35 minute protocol |