Improving 24-hour Blood Pressure Stability in Spinal Cord Injury With Low Oxygen Therapy

Phase 2RecruitingNCT06691165

Glen Foster10 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

Interventions

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.

Eligibility

Sex: ALLMin age: 19 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in 24-hour blood pressure

Mean arterial blood pressure (mmHg), averaged across 24 hours

Time frame: Change from baseline of 24-hour mean arterial blood pressure at 1-day post-intervention

Secondary Outcomes

Change in 24-hour blood pressure stability

Mean arterial blood pressure (mmHg), standard deviation across 24 hours

Time frame: Change from baseline of the standard deviation of 24-hour mean arterial blood pressure at 1-day post-intervention

Change in left-ventricular contractility

Indices of load-independent pressure generation during systole: Estimated end-systolic elastance (mmHg/ml); end-systolic pressure-volume relationship slopes (mmHg/ml)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Change in renal blood flow velocity from baseline during the first and final hypoxia cycles on the first session of the intervention