The Nitrite and Coronary Flow Study

The Vascular Effects of Nitrite on Coronary Flow Under Normoxia and Hypoxia

This study is a pharmacodynamic proof of concept study investigating the physiological effects of systemic infusion of nitrite on coronary blood flow using MRI.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Hypoxia; Vasodilation
• Intervention / Treatment: Drug: Sodium Nitrite

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).

At the end of the study the participant will have blood taken and this will be analysed for repeat levels of nitrate, nitrite and nitroso species.

All interventions will be performed by fully trained and competent medical staff.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7TJ
      • University of East Anglia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, aged greater than or equal to 18 years
2. Not known to have any significant past medical history and not having regular follow up
3. Able to provide informed consent

Exclusion Criteria:

1. 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.
2. Known allergy or intolerance to Nitrites
3. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency detected at screening in males of African, Asian or Mediterranean decent
4. 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
5. 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
6. Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease
7. Any contra-indication to MRI, including the presence of an implanted metal device or suspected metal foreign bodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium nitrite	Drug: Sodium Nitrite; Intravenous nitrite sodium infusion, dose 70μmol, of 5 minute duration (14μmol /min-1).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	All data and images collected on study day within a 2-hour time window. All study days are now complete.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in systemic levels of nitrate, nitrite and nitroso species after intravenous sodium nitrite infusion	This is anticipated to take place within 1 year of completion of the study via ozone-based chemiluminescence or high performance liquid chromatography. The data will show the change in nitrate, nitrite and nitroso species levels in the study participants plasma before and after the nitrite infusion.	Anticipated within 1 year of study completion

Collaborators and Investigators

• Sponsor: University of East Anglia
• Collaborators: Royal Brompton & Harefield NHS Foundation Trust
• Investigators: Principal Investigator: Michael P Frenneaux, FRCP (UK), University of East Anglia

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Cardiovascular Diseases; Hypoxia
• Other Study ID Numbers: 228798

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No