Clinical trial NCT06691165: Improving 24-hour Blood Pressure Stability in Spinal Cord Injury with Low Oxygen Therapy
Official title: Low Oxygen Therapy As a Cardiac Treatment for Improving 24-hour Blood Pressure Stability in Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injury
Keywords: Low oxygen therapy
Intermittent hypoxia
Blood pressure
Spinal cord injury
Cardiac function
Sympathetic nervous system
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2024-11-15
Enrollment: 10
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study examines the effects of low oxygen therapy (LOT) on the stability of 24-hour blood pressure in persons with chronic cervical spinal cord injury.

This study will examine if brief episodes of breathing lower oxygen, termed low oxygen therapy (LOT), which has been shown to enhance autonomic nervous system activity, can improve blood pressure stability in individuals with spinal cord injury. The research team will assess 24-hour blood pressure, as well as cardiac, vascular, and autonomic function before and after a 4-day LOT treatment intervention. This study will advance current understanding of treatments to mitigate cardiovascular disease risk in people with spinal cord injuries.

Detailed description: Spinal cord injury (SCI) interrupts signals travelling down from the brain to the rest of the body below the level of the injury. The loss of nerve connections involved in cardiovascular control results in blood pressure instability. This can lead to sudden drops in blood pressure, such as when shifting upright or during transfers, or sudden increases during autonomic dysreflexia. These swings in blood pressure are linked to a nearly 4-fold increase in the risk of cardiovascular disease in people with SCI.

Repeated, brief exposure to breathing lower levels of oxygen, termed low oxygen therapy, has been shown to stimulate adaptation in the nervous system. This neuroplasticity increases the activity of cardiovascular control circuits, and has been shown to increase blood pressure in able-bodied individuals. Similar effects on respiratory and motor function in people with SCI, but the effects on the cardiovascular system have not been studied in this population.

This study will test the effects of a 4-day low oxygen therapy intervention on 24-hour blood pressure stability in people with chronic cervical SCI. By assessing mechanisms of cardiac, vascular, and autonomic function, this study aims to improve current understanding of the therapeutic potential of low oxygen therapy to mitigate cardiovascular disease risk in SCI.

Eligibility criteria: Inclusion Criteria:

* Are between the ages of 19-65
* Living with a chronic cervical (at or above T1) spinal cord injury of at least one year
* Are fluent in english

Exclusion Criteria:

* High-cervical injuries requiring ventilator assistance to breathe will be excluded on account of the necessity of the facemask for the delivery of hypoxia
* Unhealed fracture, contracture, or pressure sore that might interfere with participants' ability to complete the protocol
* Additional concurrent neurological conditions (e.g., multiple sclerosis, Parkinson disease, stroke or brain injury)
* Uncontrolled cardiovascular or pulmonary disease
* Severe neuropathic pain
* Severe recurrent autonomic dysreflexia
* History of seizure disorders
* Known pregnancy

Primary outcomes:
measure: Change in 24-hour blood pressure
timeFrame: Change from baseline of 24-hour mean arterial blood pressure at 1-day post-intervention
Secondary outcomes:
measure: Change in 24-hour blood pressure stability
timeFrame: Change from baseline of the standard deviation of 24-hour mean arterial blood pressure at 1-day post-intervention
measure: Change in left-ventricular contractility
timeFrame: Change from baseline of left ventricular contractility indices immediately after the first intervention session, and at 1-day and 4-days post-intervention
measure: Change in baroreflex gain
timeFrame: Change from baseline of baroreflex gain indices immediately after first intervention session, and at 1-day and 4-days post-intervention
measure: Change in circulating catecholamines
timeFrame: Change from baseline of circulating catecholamines immediately after first intervention session, and at 1-day and 4-days post-intervention
measure: Change in cerebral neurovascular coupling and autoregulation
timeFrame: Change from baseline of the responses of cerebral blood flow indices during a visual stimulus and head-up tilt immediately after first intervention session, and at 1-day and 4-days post-intervention
measure: Change in renal filtration function
timeFrame: Change from baseline in renal biomarkers and blood flow at rest immediately after first intervention session, and at 1-day and 4-days post-intervention
measure: Change in flow-mediated dilation
timeFrame: Change from baseline in flow-mediated dilation immediately after first intervention session, and at 1-day and 4-days post-intervention
measure: Change in tonic peripheral chemoreflex activity
timeFrame: Change from baseline in the magnitude of ventilatory depression in hyperoxia immediately after first intervention session, and at 1-day and 4-days post-intervention
measure: Change in renal vascular function
timeFrame: Change in renal blood flow velocity from baseline during the first and final hypoxia cycles on the first session of the intervention
Other outcomes:
Locations:
Study officials:
References:
citation: Vermeulen TD, Benbaruj J, Brown CV, Shafer BM, Floras JS, Foster GE. Peripheral chemoreflex contribution to ventilatory long-term facilitation induced by acute intermittent hypercapnic hypoxia in males and females. J Physiol. 2020 Oct;598(20):4713-4730. doi: 10.1113/JP280458. Epub 2020 Aug 19.
citation: Claydon VE, Steeves JD, Krassioukov A. Orthostatic hypotension following spinal cord injury: understanding clinical pathophysiology. Spinal Cord. 2006 Jun;44(6):341-51. doi: 10.1038/sj.sc.3101855. Epub 2005 Nov 22.
citation: Vose AK, Welch JF, Nair J, Dale EA, Fox EJ, Muir GD, Trumbower RD, Mitchell GS. Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Exp Neurol. 2022 Jan;347:113891. doi: 10.1016/j.expneurol.2021.113891. Epub 2021 Oct 9.
citation: Perim RR, Vinit S, Mitchell GS. Cervical spinal hemisection effects on spinal tissue oxygenation and long-term facilitation of phrenic, renal and splanchnic sympathetic nerve activity. Exp Neurol. 2023 Oct;368:114478. doi: 10.1016/j.expneurol.2023.114478. Epub 2023 Jul 13.
citation: Welch JF, Vose AK, Cavka K, Brunetti G, DeMark LA, Snyder H, Wauneka CN, Tonuzi G, Nair J, Mitchell GS, Fox EJ. Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury. J Neurotrauma. 2024 Sep;41(17-18):2114-2124. doi: 10.1089/neu.2023.0353. Epub 2024 Apr 18.