Measuring the Neurological Benefits of Intermittent Hypoxia Therapy With MRI

Spinal Cord Injuries Clinical Trial

Official title:

Neurovascular Mechanisms of Intermittent Hypoxia Induced Neural Plasticity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05183113
• Other study ID #: SP0051925
• Status: Completed
• Phase: N/A
• Start date: May 20, 2019
• Est. completion date: July 30, 2023

Study information

• Verified date: September 2023
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: July 30, 2023
• Est. primary completion date: July 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypoxia
• Spinal Cord Injuries

Intervention

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.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Shirley Ryan AbilityLab

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Immediately before and ~ 1-hour after AIH on the same day
Primary	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.	Immediately before and ~ 1-hour after AIH on the same day