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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Stroke; Sleep Disorder; Sleep Apnea; Blood Pressure; Endothelial Dysfunction; Oxidative Stress; Obstructive Sleep Apnea of Adult; Hypoxia, Brain
• Intervention / Treatment: 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

Detailed Description

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
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Recruiting
      • University of Calgary
      • Contact: Chair, Conjoint Ethics Board; Phone Number: chreb@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CBF Lowering and Normoxia Sleep; 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; The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Normoxia Exposure; Other Names: Cerebral Blood Flow changes and Normoxia Sleep
Experimental: CBF Lowering and IH Sleep; 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; The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Intermittent Hypoxia (IH) Exposure; Other Names: CBF changes and Intermittent Hypoxia Sleep
Sham Comparator: Placebo and Normoxia Sleep; 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; The study participants will take Placebo and sleep under Normoxia Exposure; Other Names: Cerebral Blood Flow (CBF) with Placebo in Normoxia Sleep
Placebo Comparator: Placebo and IH Sleep; 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; The study participants will take Placebo and sleep under Intermittent Hypoxia (IH) Exposure; Other Names: CBF with Placebo in Intermittent Hypoxia Sleep

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: August 6, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stroke; Sleep Apnea Syndromes; Sleep Wake Disorders; Hypoxia, Brain; Amino Acids, Peptides, and Proteins; Proteins; Circulatory and Respiratory Physiological Phenomena; Cardiovascular Physiological Phenomena; Transcription Factors; Blood Circulation; Cerebrovascular Circulation; Core Binding Factors
• Other Study ID Numbers: REB13-0880

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No