Improving Human Cerebrovascular Function Using Acute Intermittent Hypoxia

This study uses magnetic resonance imaging to determine whether 3 weeks of repeated exposure to Acute Intermittent Hypoxia can improve brain blood flow or blood flow regulation in healthy adults.

Study Overview

• Status: Recruiting
• Conditions: Healthy Brain Perfusion
• Intervention / Treatment: Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia

Detailed Description

This study aims to identify an intervention to improve the function of blood vessels in the human brain, in order to mitigate damage to overall brain function and improve health outcomes across the lifespan. Hypoxia is a potent driver of angiogenesis and vascular plasticity, and acute intermittent hypoxia (AIH) protocols, in which an individual alternates between breathing mildly hypoxic air and normal air, are being rigorously examined for their potential in improving human physiology. This study tests whether AIH evokes beneficial vascular plasticity in the human brain, using a randomized crossover design to determine the impact of different daily AIH or sham interventions on MRI measures of cerebrovascular physiology.

Healthy, able-bodied participants between 21 and 50 years old will be invited to participate in this study. The daily AIH intervention consists of repeated visits to the PI laboratory over a three-week period to have an AIH or sham protocol administered via a hypoxia generator and face mask (Hyp-123, Hypoxico). Blood pressure readings will be taken before and after all intervention visits, and SpO2 levels continuously recorded for safety monitoring.

The effectiveness of the different interventions at improving cerebrovascular function will be assessed using MRI. In the week prior to each intervention period the participant will undergo MRI scanning. In addition to structural and diffusion weighted scans, multiple perfusion metrics will be extracted. Whole-brain cerebral blood flow will be measured using phase-contrast MRI, and quantitative CBF maps of regional perfusion will be measured using arterial spin labeling MRI. These perfusion metrics will be acquired three times: during normoxic (baseline), hypoxic, and hypercapnic conditions. Changes in perfusion values during gas challenges will measure whole-brain and regional cerebrovascular reactivity. The MRI protocol will be repeated one day after the last intervention visit.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hannah Johnson; Phone Number: (312) 373-0730; Email: AIHvasc@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Molly Bright, DPhil
      • Contact: Hannah Johnson, BA; Phone Number: 312-373-0730; Email: AIHvasc@northwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy volunteers between ages of 21 and 50 years
• No known neurological, respiratory or vascular conditions
• Safe to be scanned using MRI
• Able to communicate in English

Exclusion Criteria:

• MRI contraindications as indicated on MRI safety screening form
• Subjects with pacemakers, cochlear (in the ear) implants, or aneurysm clips or subjects who have worked with metal
• Pregnant women
• Individuals with known neurological or vascular conditions
• Individuals with sleep apnea, emphysema, or other respiratory conditions
• Individuals with severe claustrophobia
• Subjects unwilling or unable to give written informed consent in English
• Prisoners
• Frequent smoker
• Allergy to Tegaderm
• Blood pressure greater than 140/90 or less than 90/55.
• Individuals who report headaches, feeling dizzy or light-headed, or have heart palpitations on the day of the study.
• Individuals prescribed Aripiprazole and/or Lamotrigine*

Note, mild (well-controlled) asthma is not immediate grounds for exclusion.

*Other prescription medications may be grounds for exclusion; prescription medication information will be acquired during initial screening and at subsequent follow-up visits

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intermittent Hypoxia; Participant will visit our center 2-4 times per week for three weeks to receive Acute Intermittent Hypoxia.	Other: Acute Intermittent Hypoxia; Participants will wear a non-rebreathing face mask and alternate between breathing 9% O2 gas mixture for up to 1 minute, or until the target SpO2 of 85 percent is reached, and normal room air (21 percent O2) until 2 minutes are complete. This cycle will be repeated 15 times, resulting in a 30-minute protocol.
Sham Comparator: Sham Intermittent Hypoxia; Participants will visit our center 2-4 times per week for three weeks to receive Sham Intermittent Hypoxia.	Other: Sham Acute Intermittent Hypoxia; Participants will wear a non-rebreathing face mask and breathe normal air (21 percent O2) for 30-minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting cerebral blood flow	Phase-contrast MRI and Arterial Spin Labeling MRI will be used to quantify whole-brain and cortical gray matter perfusion (ml/100g/min) before and after the 3-week intervention.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrovascular reactivity	Phase-contrast MRI and Arterial Spin Labeling MRI will be used to quantify the change in perfusion caused by a vasodilatory gas challenge (inhaled hypoxia or hypercapnia), before and after the 3-week intervention.	4 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Molly G Bright, DPhil, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Perfusion; Cerebral Blood Flow; Cerebrovascular Reactivity; Acute Intermittent Hypoxia
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: STU00215559

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: MR imaging data and the associated physiologic data collected during MRI scanning will be shared in an anonymized format, along with the extracted quantitative perfusion maps and cerebrovascular reactivity maps. These data will be made available to public through the Open Science Framework (osf.io) or similar public repository. Code will be made available through the PI's laboratory Github account. A link to these resources will be included with publications resulting from this study to facilitate access.
• IPD Sharing Time Frame: At time of publication (or within one year of project completion, whichever occurs first).
• IPD Sharing Access Criteria: Data will be anonymized and made publicly available, and at that time no approval is needed and therefore there are no access criteria.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No