None listed
Conditions
Brief summary
Although stroke is among the most common causes of mortality and morbidity in New Zealand, there is limited options for improving stroke outcome at the ambulance-level. We and others have recently shown nitric oxide (NO) and argon can significantly reduce infarct volume in animal models of ischaemic stroke. Building on this, the goal of this research is to identify novel treatments to improve patient outcome following stroke. Using brachial blood pressure (BP), duplex and transcranial Doppler sonography to measure cerebral blood flow (CBF), we will determine the effects of nebulized sodium nitrite (an NO donor) and argon inhalation on blood pressure control and cerebral haemodyanmics in healthy individuals and hypertensive patients. We will test the hypotheses that 1) nebulized sodium nitrite will enhance blood pressure and cerebral blood flow control; and 2) argon gas inhalation will not significantly impact blood pressure or cerebral blood flow. Insights gained from this research will lay the foundation for future clinical trials to examine the use of argon to slow the progression of brain injury, which will significantly improve how acute stroke is treated and managed within New Zealand.
Interventions
The participants will undergo 5 min nebulized sodium nitrite (45 mg & 90 mg) with a nebuliser mask and 2 hour argon gas inhalation (79% argon and 21% oxygen) with a mouthpiece in a single-blinded manner with a 7 day washout period. Research staff will be present to monitor adherence to the intervention. These doses have been shown to be safe in healthy cohorts as well as clinical groups.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Patients with essential hypertension (At least Stage 2 hypertension; untreated office systolic blood pressure (SBP) greater than or equal to 140 mmHg or diastolic blood pressure (DBP_ greater than or equal to 90 mmHg); Patients with chronic atrial fibrillation, as established on ECG or Holter monitoring Normotensive controls (office SBP less than or equal to 120 mmHg and DBP less than or equal to 80 mmHg); Aged over 18 years; Body mass index less than 35 kg/m2.
Exclusion criteria
Hemodynamically significant valvular heart disease (excluding atrial fibrillation e.g., stenosis, mechanical valve replacement) Severe left ventricular systolic dysfunction Recent acute coronary syndrome (<12 months) (e.g., myocardiac infarction, angioplasty, unstable angina) Previous coronary artery bypass surgery Secondary causes of hypertension (e.g., phaeochromocytoma) Recent stroke/transient ischaemic attack (<12 months) Current smoker Body mass index <18 kg/m2. Current pregnancy Current user of recreational drugs Current abuser of alcohol Inability to fully or appropriately provide consent (e.g., language issue, reading capability) Underlying medical conditions, which in the opinion of the Investigator place the participant at unacceptably high risk for participating in the study. Chronic and systemic illness including: Severe respiratory disease (e.g., chronic obstructive pulmonary disease); Severe, uncontrolled type II diabetes; Current treatment for cancer or complete remission <5 years Connective tissue or inflammatory disease Neurological / psychiatric disease (e.g., peripheral neuropathy, dementia, Parkisnon’s, epilepsy) Infection or pyrexial illness Uncontrolled thyroid disorders Renal impairment (e.g., glomerulus filtration rate less than 60) Liver disease
Outcome results
None listed