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Measuring the Neurological Benefits of Intermittent Hypoxia Therapy With MRI

Primary Purpose

Spinal Cord Injuries

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Acute Intermittent Hypoxia

About this trial

This is an interventional basic science trial for Spinal Cord Injuries focused on measuring Spinal Cord Injury, Acute Intermittent Hypoxia, Magnetic Resonance Imaging

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

All participants must meet the following inclusion criteria:

Between the ages of 18-60 years
Safe to be scanned using MRI
Able to communicate in English
Ability to sign informed consent

In addition, the participants recruited with SCI must meet the following criteria:

History of a traumatic spinal cord injury, inclusive of levels C2-T1
At least 6 months since onset of spinal cord injury
Cause of the spinal cord injury was non-progressive
Ability to complete and comply with information within the informed consent
Ability to close and open at least one hand without assistance

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
Women who are currently pregnant, nursing, or planning on becoming pregnant
Individuals with severe claustrophobia
Subjects unwilling or unable to give written informed consent in English
Prisoners
Frequent smokers (greater than 5 cigarettes per day)
Blood pressure greater than 160/110 or less than 85/55.
Individuals who report headaches, feeling dizzy or light-headed, or have heart palpitations on the day of the study.
Diagnosis of any of the following comorbid conditions: congestive heart failure, cardiac arrhythmias, uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, emphysema, severe asthma, previous myocardial infraction or known carotid/intracerebral artery stenosis, presence of active deep venous thrombosis, or cancer.
Individuals who utilize mechanical ventilation or have a tracheostomy
Individuals who utilize an intrathecal baclofen pump
Orthopedic injury affecting upper extremities
Currently participating in any other hypoxia related study.

Sites / Locations

Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acute Intermittent Hypoxia

Arm Description

Both healthy participants and those with spinal cord injury will receive the acute intermittent hypoxia (AIH) intervention. All participants are imaged pre- and post-AIH intervention, and thus serve as a self-comparison to observe the hypothesized improvement in bilateral hand strength.

Outcomes

Primary Outcome Measures

BOLD fMRI activation in motor cortex during isometric hand grip tasks

Assess AIH-induced changes in %BOLD activation within the left and right motor cortices during unilateral isometric hand grasping tasks targeting submaximal force levels with real-time feedback.

BOLD fMRI vascular reactivity to a breath-hold task

Measurements of breath-hold induced vasodilation (vascular reactivity, in units of %BOLD/mmHg end-tidal CO2) acquired via functional MRI in the brain and spinal cord.

Secondary Outcome Measures

Full Information

NCT ID

NCT05183113

First Posted

December 7, 2021

Last Updated

September 26, 2023

Sponsor

Northwestern University

Collaborators

Shirley Ryan AbilityLab

1. Study Identification

Unique Protocol Identification Number

NCT05183113

Brief Title

Measuring the Neurological Benefits of Intermittent Hypoxia Therapy With MRI

Official Title

Neurovascular Mechanisms of Intermittent Hypoxia Induced Neural Plasticity

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

May 20, 2019 (Actual)

Primary Completion Date

July 30, 2023 (Actual)

Study Completion Date

July 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

Shirley Ryan AbilityLab

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

This study uses Magnetic Resonance Imaging to image the brain and spinal cord before and after an Intermittent Hypoxia intervention. Acquiring these scans in patients with chronic cervical spinal cord injury and uninjured controls will enable characterization of changes in neurovascular physiology caused by this promising new therapy.

Detailed Description

Acute intermittent hypoxia (AIH) is an emerging, safe technique for facilitating neural plasticity in individuals with chronic spinal cord injury (SCI), demonstrating significant transient improvements in respiratory function, plantar flexion, locomotor function, and hand dexterity and strength. Although these studies observe some degree of success eliciting plasticity, we lack a framework for systematic optimization of the AIH protocol for individual patients. Better understanding of what physiological mechanisms drive AIH-induced neural plasticity in humans will directly inform the development of AIH as an effective treatment option in chronic SCI. This study applies magnetic resonance imaging (MRI) to test how AIH influences vascular and neural properties of the brain and spinal cord. Individuals with SCI and uninjured participants will be recruited to undergo two MRI scan sessions on one day. In between these scan sessions, participants will undergo a single 30-minute session of AIH. In each scan session, functional MRI will assess AIH-induced changes in neural activation patterns during motor tasks (unilateral isometric hand grasping tasks) and vascular reactivity to breath hold tasks (transient hypocapnia to induce vasodilation). Additional structural scans will be acquired to aid in image analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Cord Injuries

Keywords

Spinal Cord Injury, Acute Intermittent Hypoxia, Magnetic Resonance Imaging

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Acute Intermittent Hypoxia

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Acute Intermittent Hypoxia

Intervention Description

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.

Primary Outcome Measure Information:

Title

BOLD fMRI activation in motor cortex during isometric hand grip tasks

Description

Assess AIH-induced changes in %BOLD activation within the left and right motor cortices during unilateral isometric hand grasping tasks targeting submaximal force levels with real-time feedback.

Time Frame

Immediately before and ~ 1-hour after AIH on the same day

Title

BOLD fMRI vascular reactivity to a breath-hold task

Description

Measurements of breath-hold induced vasodilation (vascular reactivity, in units of %BOLD/mmHg end-tidal CO2) acquired via functional MRI in the brain and spinal cord.

Time Frame

Immediately before and ~ 1-hour after AIH on the same day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All participants must meet the following inclusion criteria: Between the ages of 18-60 years Safe to be scanned using MRI Able to communicate in English Ability to sign informed consent In addition, the participants recruited with SCI must meet the following criteria: History of a traumatic spinal cord injury, inclusive of levels C2-T1 At least 6 months since onset of spinal cord injury Cause of the spinal cord injury was non-progressive Ability to complete and comply with information within the informed consent Ability to close and open at least one hand without assistance 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 Women who are currently pregnant, nursing, or planning on becoming pregnant Individuals with severe claustrophobia Subjects unwilling or unable to give written informed consent in English Prisoners Frequent smokers (greater than 5 cigarettes per day) Blood pressure greater than 160/110 or less than 85/55. Individuals who report headaches, feeling dizzy or light-headed, or have heart palpitations on the day of the study. Diagnosis of any of the following comorbid conditions: congestive heart failure, cardiac arrhythmias, uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, emphysema, severe asthma, previous myocardial infraction or known carotid/intracerebral artery stenosis, presence of active deep venous thrombosis, or cancer. Individuals who utilize mechanical ventilation or have a tracheostomy Individuals who utilize an intrathecal baclofen pump Orthopedic injury affecting upper extremities Currently participating in any other hypoxia related study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Molly G Bright, DPhil

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

MR imaging data and the associated physiologic data collected during MRI scanning will be shared in an anonymized format. These data will be made available to public through the Open Science Framework (osf.io) or similar public repository.

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.

Citations:

PubMed Identifier

15772352

Citation

Golder FJ, Mitchell GS. Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury. J Neurosci. 2005 Mar 16;25(11):2925-32. doi: 10.1523/JNEUROSCI.0148-05.2005.

Results Reference

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PubMed Identifier

28972191

Citation

Trumbower RD, Hayes HB, Mitchell GS, Wolf SL, Stahl VA. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Neurology. 2017 Oct 31;89(18):1904-1907. doi: 10.1212/WNL.0000000000004596. Epub 2017 Sep 29.

Results Reference

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PubMed Identifier

21821826

Citation

Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.

Results Reference

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PubMed Identifier

24285617

Citation

Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27.

Results Reference

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PubMed Identifier

28459438

Citation

Li Y, Lucas-Osma AM, Black S, Bandet MV, Stephens MJ, Vavrek R, Sanelli L, Fenrich KK, Di Narzo AF, Dracheva S, Winship IR, Fouad K, Bennett DJ. Pericytes impair capillary blood flow and motor function after chronic spinal cord injury. Nat Med. 2017 Jun;23(6):733-741. doi: 10.1038/nm.4331. Epub 2017 May 1.

Results Reference

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Measuring the Neurological Benefits of Intermittent Hypoxia Therapy With MRI

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