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

University of Calgary12 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Obstructive Sleep Apnea of Adult Hypoxia, Brain

Interventions

Drug Lowering Cerebral Blood Flow (CBF) and Normoxia SleepDRUG

The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Normoxia Exposure

Drug Lowering CBF and Intermittent Hypoxia SleepDRUG

The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Intermittent Hypoxia (IH) Exposure

Placebo and Normoxia SleepDRUG

The study participants will take Placebo and sleep under Normoxia Exposure

Placebo and Intermittent Hypoxia SleepDRUG

The study participants will take Placebo and sleep under Intermittent Hypoxia (IH) Exposure

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: ~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.

Time frame: ~18 months (from the starting time of recruiting study participants)

Secondary Outcomes

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.

Time frame: ~24 months (from the starting time of recruiting study participants)