Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| F23-01237 | Other Grant/Funding Number | Canadian Institutes of Health Research |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Room air control; lot oxygen therapy; recovery/washout | Experimental | Participants with chronic cervical spinal cord injury will undergo a 4-day low oxygen therapy intervention. Measurements will first be taken at least three days before the beginning of the intervention to establish baseline characteristics, immediately before and after the first day of the intervention to assess the acute response to the intervention, and on the first and fourth days after the end of the intervention to assess persistent effects and washout. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low oxygen therapy (LOT) | Drug | Participants will breathe variable concentrations of inspired oxygen, carbon dioxide, and nitrogen. The concentrations will be adjusted on a breath-by-breath basis to maintain end-tidal targets. Each daily session of the intervention will consist of forty 1-minute intervals. Each 1-minute interval will consist of 40 seconds of hypercapnic hypoxia, increasing the partial pressure of end-tidal carbon dioxide by +4 mmHg and decreasing the partial pressure of end-tidal oxygen to 45 mmHg, followed by 20 seconds in simulated room air to return to baseline carbon dioxide and oxygen levels. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 24-hour blood pressure | Mean arterial blood pressure (mmHg), averaged across 24 hours | Change from baseline of 24-hour mean arterial blood pressure at 1-day post-intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 24-hour blood pressure stability | Mean arterial blood pressure (mmHg), standard deviation across 24 hours | Change from baseline of the standard deviation of 24-hour mean arterial blood pressure at 1-day post-intervention |
| Change in left-ventricular contractility |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Scott F Thrall, M.Sc. | Contact | +1 250-807-8083 | sthrall@student.ubc.ca | |
| Glen E Foster, Ph.D. | Contact | +1 250-807-8224 | glen.foster@ubc.ca |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UBC Okanagan | Recruiting | Kelowna | British Columbia | V1V 1V7 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32744340 | Background | 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. | |
| 16304564 | Background |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
Indices of load-independent pressure generation during systole: Estimated end-systolic elastance (mmHg/ml); end-systolic pressure-volume relationship slopes (mmHg/ml) |
| Change from baseline of left ventricular contractility indices immediately after the first intervention session, and at 1-day and 4-days post-intervention |
| Change in baroreflex gain | Indices of baroreflex sensitivity: Relationship of systolic blood pressure against subsequent R-R interval duration during Valsalva Maneuver phases II and IV (ms/mmHg); spectral power of low-frequency resting blood pressure variability | Change from baseline of baroreflex gain indices immediately after first intervention session, and at 1-day and 4-days post-intervention |
| Change in circulating catecholamines | Venous plasma concentrations of norepinephrine and epinephrine (mmol/L) | Change from baseline of circulating catecholamines immediately after first intervention session, and at 1-day and 4-days post-intervention |
| Change in cerebral neurovascular coupling and autoregulation | Middle and posterior cerebral artery blood flow velocity (cm/s) | 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 |
| Change in renal filtration function | Humoral renal biomarkers (e.g., serum creatinine) | 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 |
| Change in flow-mediated dilation | Brachial artery flow-mediated dilation following 5-minute forearm blood flow occlusion (mm) | Change from baseline in flow-mediated dilation immediately after first intervention session, and at 1-day and 4-days post-intervention |
| Change in tonic peripheral chemoreflex activity | Magnitude of hyperoxic ventilatory depression (L/min) | 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 |
| Change in renal vascular function | Renal artery blood flow velocity (cm/s) | Change in renal blood flow velocity from baseline during the first and final hypoxia cycles on the first session of the intervention |
| International Collaboration on Repair Discoveries (ICORD) | Recruiting | Vancouver | British Columbia | V5Z 1N1 | Canada |
|
| 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. |
| 34637802 | Background | 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. |
| 37451584 | Background | 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. |
| 38468543 | Background | 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. |
| D014947 | Wounds and Injuries |