Safety and potential benefits of acute intermittent hypoxia in people with chronic traumatic brain injury

Background Acute intermittent hypoxia (AIH) was recently demonstrated to improve motor and cognitive function in several patient populations, including incomplete spinal cord injury, stroke, multiple sclerosis and mild cognitive impairment.

Our clinical trial aimed to establish if AIH can be safely administered in patients with traumatic brain injury (TBI) and to collect preliminary data about its potential efficacy for treating motor, cognitive and affective sequelae of TBI.

Twelve volunteers with chronic TBI underwent four AIH sessions conducted on separate days, in which they were exposed to fifteen 30-60-s hypoxic episodes interspersed with 60-90 s of breathing ambient air. Inspired oxygen (O2) concentration during hypoxic episodes was gradually reduced from 21% (equal to ambient air, sham), to 17%, 13%, and 9%, over the course of four sessions. Neuropsychological and motor tests were administered on days before and after AIH, as well as 60 min after each AIH session. In addition, transcranial magnetic stimulation (TMS) was applied to the hand motor area 45 min after the first (21% O2) and last (9% O2) AIH session.

All participants tolerated the AIH sessions well and were able to complete the entire protocol. No significant improvement in cognition or mood was noted after the AIH intervention. Motor performance gradually improved over the course of the study, but no significant changes in response to TMS were found in corticospinal excitability.

AIH dosage as low as 9% O2 appears safe to use in chronic TBI, but its potential benefits remain to be investigated. Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT04890639 Funding Statement The clinical trial was funded by the Exploratory Neuroscience Research Grant from the National Institute of Neurological Disorders and Stroke (National Institutes of Health) No. R21 NS1148150-01A1. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Northwestern University Institutional Review Board gave ethical approval for this work (IRB protocol #STU00213969). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request.