The Vascular Effects of Nitrite on Coronary Flow Under Normoxia and Hypoxia
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University of East Anglia
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- The effect of systemic sodium nitrite on the degree of vasorelaxation (captured by taking 4 sets of MRI images on the same study day, within a 2-hour window) in the coronary vessels in normoxia and hypoxia in healthy participants
Study Overview
Brief Summary
This study is a pharmacodynamic proof of concept study investigating the physiological effects of systemic infusion of nitrite on coronary blood flow using MRI.
Detailed Description
This is a healthy volunteer, proof of concept study.
The participant will have blood taken and this will be analysed for baseline levels of nitrate, nitrite and nitroso species. They will then have a baseline MRI to assess coronary flow in normoxia. Next, hypoxia will be induced using 12% oxygen/88% nitrogen. The participant will then have a baseline MRI to assess coronary flow in hypoxia (3 breath-hold image captures).
After all baseline images have been captured, the investigators will commence an intravenous nitrite sodium infusion, dose 70μmol, of 5 minute duration (14μmol /min-1). At the 5th minute, the participant have a further MRI image to assess coronary flow with the intervention in normoxia (3 breath-hold image captures).
A 10-minute washout will follow (with the half-life of nitrite being documented as 110 seconds). There will be optional repeat 3 breath-hold image captures at 5 minutes and at 10 minutes.
Next hypoxia will be induced using 12% oxygen/88% nitrogen again. The investigators will commence a second intravenous nitrite sodium infusion, dose 70μmol, 5 minute duration (14μmol /min-1). At the 5th minute, the participant will have a further MRI image to assess coronary flow with the intervention in hypoxia (3 breath-hold image captures).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female, aged greater than or equal to 18 years
- •Not known to have any significant past medical history and not having regular follow up
- •Able to provide informed consent
Exclusion Criteria
- •Significant medical, surgical or psychiatric disease that in the opinion of the Clinical Research Fellow would affect subject safety or significantly impact his/her ability to comply with follow-up. This would include any known clotting disorders.
- •Known allergy or intolerance to Nitrites
- •Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency detected at screening in males of African, Asian or Mediterranean decent
- •Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to enrolment
- •Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the drug half-life, whichever is the longer
- •Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease
- •Any contra-indication to MRI, including the presence of an implanted metal device or suspected metal foreign bodies
Arms & Interventions
Sodium nitrite
Intervention: Sodium Nitrite (Drug)
Outcomes
Primary Outcomes
The effect of systemic sodium nitrite on the degree of vasorelaxation (captured by taking 4 sets of MRI images on the same study day, within a 2-hour window) in the coronary vessels in normoxia and hypoxia in healthy participants
Time Frame: All data and images collected on study day within a 2-hour time window. All study days are now complete.
This will be measured on the study day through the acquisition of 4 set of separate MRI images (each image set acquisition duration 3-5 minutes). 4 conditions for image acquisition: normoxia without nitrite, hypoxia without nitrite, normoxia with nitrite and hypoxia with nitrite. Images captured using coronary MRI.
Secondary Outcomes
- The change in systemic levels of nitrate, nitrite and nitroso species after intravenous sodium nitrite infusion(Anticipated within 1 year of study completion)