Cerebral Blood Flow and Ventilatory Responses During Sleep in Normoxia and Intermittent Hypoxia

Study Overview
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Brief Summary
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A prospective double blind, placebo-controlled, randomized cross-over trial to evaluate the effect of lowering cerebral blood flow on the ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses).

Detailed Description
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The investigators will explore the relationship between changes in Cerebral Blood Flow (CBF) and ventilatory chemoreflexes i.e. Acute Ventilatory Response to Hypoxia (AHVR) and Acute Hypercapnic Ventilatory Response (HCVR) before, during and after sleep under normoxic conditions and sleep accompanied by isocapnic Intermittent Hypoxia (IH) among healthy human study participants. A pharmacological intervention will be utilized to manipulate the CBF in a randomized order. The study participants will also be randomly assigned the order to sleep either under normoxia or IH exposure. The experiments will be separated from one another with an interval of sufficient drug and IH exposure washout period. The venous blood samples and urinary samples will be collected for the vascular biomarkers.

Official Title
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Role of Cerebral Blood Flow on Ventilatory Stability During Sleep in Normoxia and Intermittent Hypoxia

Conditions
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Blood Pressure, Obstructive Sleep Apnea of Adult, Hypoxia, Brain, Sleep Apnea, Sleep Disorder, Stroke, Endothelial Dysfunction, Oxidative Stress

Intervention / Treatment
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* Drug: Drug Lowering Cerebral Blood Flow (CBF) and Normoxia Sleep
* Drug: Drug Lowering CBF and Intermittent Hypoxia Sleep
* Drug: Placebo and Normoxia Sleep
* Drug: Placebo and Intermittent Hypoxia Sleep


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18 - 45 years of age Living in Calgary for the past one year Have no medical condition or should not be taking any blood pressure medications. The participant should not be lactose intolerant Exclusion Criteria: Cerebrovascular, cardio-respiratory, renal and metabolic diseases Bleeding disorders and upper gastrointestinal diseases e.g. peptic ulcer disease Pregnancy, obese and sleep-disordered breathing Drug allergies to non-steroidal anti-inflammatories Currently smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CBF Lowering and Normoxia Sleep<br>Study participants will take drug lowering Cerebral Blood Flow (CBF) and sleep under room air i.e. normoxia exposure. | Drug: Drug Lowering Cerebral Blood Flow (CBF) and Normoxia Sleep<br>* The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Normoxia Exposure<br>* Other names: Cerebral Blood Flow changes and Normoxia Sleep;|
| Experimental: CBF Lowering and IH Sleep<br>Study participants will take drug lowering Cerebral Blood Flow (CBF) and sleep under Intermittent Hypoxia (IH) exposure. | Drug: Drug Lowering CBF and Intermittent Hypoxia Sleep<br>* The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Intermittent Hypoxia (IH) Exposure<br>* Other names: CBF changes and Intermittent Hypoxia Sleep;|
| Sham Comparator: Placebo and Normoxia Sleep<br>Study participants will take Placebo that has no effect on Cerebral Blood Flow (CBF) and sleep under room air i.e. normoxia exposure. | Drug: Placebo and Normoxia Sleep<br>* The study participants will take Placebo and sleep under Normoxia Exposure<br>* Other names: Cerebral Blood Flow (CBF) with Placebo in Normoxia Sleep;|
| Placebo Comparator: Placebo and IH Sleep<br>Study participants will take Placebo that has no effect on Cerebral Blood Flow (CBF) and sleep under Intermittent Hypoxia (IH) exposure. | Drug: Placebo and Intermittent Hypoxia Sleep<br>* The study participants will take Placebo and sleep under Intermittent Hypoxia (IH) Exposure<br>* Other names: CBF with Placebo in Intermittent Hypoxia Sleep;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cerebral blood flow and ventilatory chemoreflexes | The relationship between changes in cerebral blood flow (CBF) and ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses) before and after sleeping under normoxia and intermittent hypoxia exposure among healthy human study participants. |  18 months (from the starting time of recruiting study participants) | 
| Cerebral blood flow responses and ventilatory chemoreflexes during sleep | The relationship between cerebral blood flow (CBF) changes and ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses) during sleep under normoxia and intermittent hypoxia exposure among healthy human study participants. |  18 months (from the starting time of recruiting study participants) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in reactive oxygen species and vascular biomarkers | The changes in vascular biomarkers such as nitric oxide, reactive oxygen species and exosome analysis or urinary prostaglandins before and after sleep under normoxia and intermittent hypoxia exposure with cerebral blood flow changes. |  24 months (from the starting time of recruiting study participants) |