Coronary Artery DiseasePhase 2NCT04001283
Nitrite Effects on Cardiac Muscle in CABG
A Phase 2 study testing Sodium Nitrite and 0.9% Sodium-chloride in people with Coronary Artery Disease and Atherosclerosis, run by University of East Anglia at 2 sites in United Kingdom.
Trial summary
The purpose of this study is to test whether sodium nitrite affects the expression of cellular proteins important for metabolic and vascular function in vascular offcuts and cardiac biopsies taken from patients undergoing coronary artery bypass grafting (CABG) surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Atherosclerosis, Vascular Diseases
- What is being tested?
- Sodium Nitrite and 0.9% Sodium-chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 21 Jan 2013to 1 Jul 2019
- Phase
- Phase 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged >18years scheduled to undergo coronary artery bypass grafting.
Who cannot join
- Inability to read and understand the consent form and patient information leaflet Pregnancy and any woman of child bearing potential Patients with Type I diabetes Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety and participation in the trial including severe heart failure (NYHAIII-IV and EF<40%) and severe renal impairment (requiring dialysis).
- Unstable coronary syndrome (within 2 weeks) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent.
- 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.
- Intended heart valve surgery or additional surgery or redo-CABG surgery.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 1 recruiting
- Completed
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB25 2ZN
- Recruiting
Papworth Hospital
Cambridge, CB2 0AY
Nicholas D Gollop, MRCP(UK), 01603 591790, n.gollop@uea.ac.uk
Stephen Large, MD, FRCS
About this study
Official title: Effect of Nitrite on Cardiac Muscle and Blood Vessels in Patients Undergoing Coronary Artery Bypass Grafting Surgery
The purpose of this study is to test whether sodium nitrite affects the expression of cellular proteins important for metabolic and vascular function in vascular offcuts and cardiac biopsies taken from patients undergoing coronary artery bypass grafting (CABG) surgery.
Read the detailed description
Nitrite has been shown in recent studies to improve cardiac performance, particularly in patients with heart failure. These improvements were demonstrated in measures that are independent of cardiac loading conditions, implying improved contractility via effects at a cellular level. In humans, coronary artery bypass graft (CABG) surgery presents an opportunity to safely obtain cardiac muscle biopsies and vascular tissue in order to investigate changes at a cellular level in these tissues.
The aim of this study is to investigate whether sodium nitrite affects the expression of cellular proteins important for heart muscle metabolism and vascular function when infused prior to routine CABG surgery. Patients undergoing CABG surgery who provide written informed consent will receive intravenous sodium nitrite 24hours prior to surgery, 30 minutes prior to surgery, or placebo. As Type 2 Diabetes Mellitus is common in patients undergoing CABG surgery, and itself has profound effects on metabolism, these patients will be sub-grouped into a diabetic cohort for interpretation of the molecular biology results. The 24hours prior to surgery vs. placebo arm will take place first, followed by the 30minutes prior to surgery vs. placebo arm. The data from this study will provide important information on the effects of nitrite on heart muscle and blood vessel tissues, and inform larger clinical trials in patients with cardiovascular disease.
- Conditions
- Coronary Artery Disease, Atherosclerosis, Vascular Diseases, Cardiac Disease, Diabetes Mellitus
- Being tested
- Sodium Nitrite, 0.9% Sodium-chloride
- Medical subject headings
- Coronary Artery Disease, Atherosclerosis, Vascular Diseases, Heart Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium NitriteDrug
Intravenous drug infusion
0.9% Sodium-chlorideDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| sodium nitrite 24hours before | Experimental | 10umol/min intravenous sodium nitrite for 30minutes at 1ml/min over a period of 30minutes, 24 hours prior to CABG surgery Receives: Drug: Sodium Nitrite |
| sodium nitrite 30minutes before | Experimental | 10umol/min intravenous sodium nitrite for 30minutes at 1ml/min over a period of 30minutes, 30 minutes prior to CABG surgery Receives: Drug: Sodium Nitrite |
| 0.9% sodium chloride | Placebo comparator | Intravenous normal (0.9%) sodium chloride infused at 1ml/min Receives: Drug: 0.9% Sodium-chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic protein expression in cardiac biopsies and vascular offcuts
Cellular proteins that are important for metabolic regulation and vascular function that may be affected by nitrite such as eNOS, AKT, PDH
Measured: Taken during CABG surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2019
- Study start21 Jan 2013
- Primary completion1 Jul 2019 (estimated)
- Study completion1 Jul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael P Frenneaux, MD, FRCP, Principal investigator, Clinical Professor, Norwich Medical School, The University of East Anglia, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04001283
- Sponsor's protocol ID
- 87012
- Status last verified
- Jun 2019
- First submitted
- 25 Jul 2017
- Last updated
- 28 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ntessalen M, Procter NEK, Schwarz K, Loudon BL, Minnion M, Fernandez BO, Vassiliou VS, Vauzour D, Madhani M, Constantin-Teodosiu D, Horowitz JD, Feelisch M, Dawson D, Crichton PG, Frenneaux MP. Inorganic nitrate and nitrite supplementation fails to improve skeletal muscle mitochondrial efficiency in mice and humans. Am J Clin Nutr. 2020 Jan 1;111(1):79-89. doi: 10.1093/ajcn/nqz245.
PubMed 31599928
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Nitrite on Cardiac Muscle and Blood Vessels in Patients Undergoing Coronary Artery Bypass Grafting Surgery
- ClinicalTrials.gov ID
- NCT04001283
- Acronym / sponsor ID
- 87012
- Conditions
- Coronary Artery Disease, Atherosclerosis, Vascular Diseases, Cardiac Disease, Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Study start
- 21 Jan 2013 (actual)
- Primary completion
- 1 Jul 2019 (estimated)
- Study completion
- 1 Jul 2019 (estimated)
- First posted
- 28 Jun 2019 (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.
The purpose of this study is to test whether sodium nitrite affects the expression of cellular proteins important for metabolic and vascular function in vascular offcuts and cardiac biopsies taken from patients undergoing coronary artery bypass grafting (CABG) surgery.
Detailed description
Nitrite has been shown in recent studies to improve cardiac performance, particularly in patients with heart failure. These improvements were demonstrated in measures that are independent of cardiac loading conditions, implying improved contractility via effects at a cellular level. In humans, coronary artery bypass graft (CABG) surgery presents an opportunity to safely obtain cardiac muscle biopsies and vascular tissue in order to investigate changes at a cellular level in these tissues.
The aim of this study is to investigate whether sodium nitrite affects the expression of cellular proteins important for heart muscle metabolism and vascular function when infused prior to routine CABG surgery. Patients undergoing CABG surgery who provide written informed consent will receive intravenous sodium nitrite 24hours prior to surgery, 30 minutes prior to surgery, or placebo. As Type 2 Diabetes Mellitus is common in patients undergoing CABG surgery, and itself has profound effects on metabolism, these patients will be sub-grouped into a diabetic cohort for interpretation of the molecular biology results. The 24hours prior to surgery vs. placebo arm will take place first, followed by the 30minutes prior to surgery vs. placebo arm. The data from this study will provide important information on the effects of nitrite on heart muscle and blood vessel tissues, and inform larger clinical trials in patients with cardiovascular disease.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| sodium nitrite 24hours before | Experimental | Drug: Sodium Nitrite10umol/min intravenous sodium nitrite for 30minutes at 1ml/min over a period of 30minutes, 24 hours prior to CABG surgery |
| sodium nitrite 30minutes before | Experimental | Drug: Sodium Nitrite10umol/min intravenous sodium nitrite for 30minutes at 1ml/min over a period of 30minutes, 30 minutes prior to CABG surgery |
| 0.9% sodium chloride | Placebo comparator | Drug: 0.9% Sodium-chlorideIntravenous normal (0.9%) sodium chloride infused at 1ml/min |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Males or females aged >18years scheduled to undergo coronary artery bypass grafting.
Key exclusion criteria (4 listed)
- Inability to read and understand the consent form and patient information leaflet Pregnancy and any woman of child bearing potential Patients with Type I diabetes Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety and participation in the trial including severe heart failure (NYHAIII-IV and EF<40%) and severe renal impairment (requiring dialysis).
- Unstable coronary syndrome (within 2 weeks) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent.
- 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.
- Intended heart valve surgery or additional surgery or redo-CABG surgery.
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 drug infusion | Drug | sodium nitrite 24hours before, sodium nitrite 30minutes before |
| 0.9% Sodium-chlorideMatched placebo | Drug | 0.9% sodium chloride |
Primary outcome
Metabolic protein expression in cardiac biopsies and vascular offcuts
Time frame: Taken during CABG surgery
Cellular proteins that are important for metabolic regulation and vascular function that may be affected by nitrite such as eNOS, AKT, PDH
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2019.
- Derived from this study: PubMed 31599928Ntessalen M, Procter NEK, Schwarz K, Loudon BL, Minnion M, Fernandez BO, Vassiliou VS, Vauzour D, Madhani M, Constantin-Teodosiu D, Horowitz JD, Feelisch M, Dawson D, Crichton PG, Frenneaux MP. Inorganic nitrate and nitrite supplementation fails to improve skeletal muscle mitochondrial efficiency in mice and humans. Am J Clin Nutr. 2020 Jan 1;111(1):79-89. doi: 10.1093/ajcn/nqz245.
- 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, MD, FRCP principal investigator
Clinical Professor, Norwich Medical School, The University of East Anglia, UK
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Nitrite and 0.9% Sodium-chloride in people with Coronary Artery Disease and Atherosclerosis, run by University of East Anglia at 2 sites 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 1 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 28 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicholas D Gollop, MRCP(UK) (01603 591790, n.gollop@uea.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic protein expression in cardiac biopsies and vascular offcuts (time frame: Taken during CABG surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04001283, which also lists 1 linked publication.
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 28 Jun 2019.