Cardiovascular DiseasesPhase 1/2NCT04354051
The Nitrite and Coronary Flow Study
A Phase 1/2 study testing Sodium Nitrite in people with Cardiovascular Diseases and Vasodilation, run by University of East Anglia at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Vasodilation, Hypoxia
- What is being tested?
- Sodium Nitrite
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2018to 1 Dec 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of East Anglia
Norwich, Norfolk, NR4 7TJ
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiovascular Diseases, Vasodilation, Hypoxia
- Being tested
- Sodium Nitrite
- Medical subject headings
- Cardiovascular Diseases, Aneurysm, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium NitriteDrug
Intravenous nitrite sodium infusion, dose 70μmol, of 5 minute duration (14μmol /min-1).
| Study group | Role | What they receive |
|---|---|---|
| Sodium nitrite | Experimental | Not described Receives: Drug: Sodium Nitrite |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: All data and images collected on study day within a 2-hour time window. All study days are now complete.
Secondary outcomes (1)
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.
Measured: Anticipated within 1 year of study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2020
- Study start1 Jul 2018
- Primary completion1 Dec 2018
- Study completion1 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Michael P Frenneaux, FRCP (UK), Principal investigator, University of East Anglia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04354051
- Sponsor's protocol ID
- 228798
- Status last verified
- Apr 2020
- First submitted
- 10 Feb 2020
- Last updated
- 21 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Vascular Effects of Nitrite on Coronary Flow Under Normoxia and Hypoxia
- ClinicalTrials.gov ID
- NCT04354051
- Acronym / sponsor ID
- 228798
- Conditions
- Cardiovascular Diseases, Vasodilation, Hypoxia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 21 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sodium nitrite | Experimental | Drug: Sodium Nitrite |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium NitriteIntravenous nitrite sodium infusion, dose 70μmol, of 5 minute duration (14μmol /min-1). | Drug | Sodium nitrite |
Primary outcome
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.
1 secondary outcome
The change in systemic levels of nitrate, nitrite and nitroso species after intravenous sodium nitrite infusion
Time frame: Anticipated within 1 year of study completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael P Frenneaux, FRCP (UK) principal investigator
University of East Anglia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sodium Nitrite in people with Cardiovascular Diseases and Vasodilation, run by University of East Anglia at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.