Investigating the effects of dietary nitrate in patients with stable angina
| ISRCTN | ISRCTN17373946 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17373946 |
| ClinicalTrials.gov number | NCT02529189 |
| Secondary identifying numbers | 20060 |
- Submission date
- 05/11/2015
- Registration date
- 05/11/2015
- Last edited
- 13/05/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Coronary heart disease (CHD), also known as ischemic heart disease, is one of the leading causes of death worldwide. CHD develops because of the build-up of fatty deposits (plaque) on the walls of the coronary arteries (the arteries that supply the heart with oxygen-rich blood). When arteries are blocked or narrowed, the heart does not receive enough blood to function properly, which can cause pain and tightness in the chest (angina), or even lead to a heart attack. There are several types of angina, the most common being stable angina (where the pain is brought on by an obvious trigger, such as exercising). An angioplasty is a common procedure in which a thin tube (catheter) is placed in the narrowed blood vessel. A small balloon on the tip of the catheter is gradually inflated to reopen the artery and flatten the blockage against the artery wall. A mesh-like tube (stent) is often placed inside the artery to keep it open (percutaneous coronary intervention). In about 5-10% of patients, the part of the artery that was reopened in the angioplasty can become narrowed again (restenosis). Nitrate is a chemical which plays an important part in regulating blood pressure and blood flow. It is commonly found in green leady vegetables and beetroot. Recent studies have shown that including nitrate in the diet could help to prevent or reduce restenosis. The aim of this study is to find out whether drinking nitrate-rich beetroot juice can help to prevent restenosis in patients who have had a percutaneous coronary intervention.
Who can participate?
Adults between 18 and 85 years with stable angina who are having an angioplasty
What does the study involve?
Participants are randomly allocated to one of two groups. Starting one day after their surgery, participants in the first group are given 70ml of beetroot juice containing a concentration of 4-5mmol nitrate every day for 6 months. Starting one day after their surgery, participants in the second group are given 70ml nitrate-depleted beetroot juice (where the nitrate has been removed from the juice) to drink every day for 6 months. At the end of the 6 months, participants in both groups are scanned to find out if there is any sign of restenosis.
What are the possible benefits and risks of participating?
Participants in the nitrate group could potentially benefit from an improvement to their cardiovascular (heart and blood vessels) health. There are no notable risks of participating in this study.
Where is the study run from?
William Harvey Research Institute, Queen Mary University of London (UK)
When is the study starting and how long is it expected to run for?
November 2015 to April 2018
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Krishnaraj Rathod
Contact information
Scientific
Barts and The London
Queen Mary's School of Medicine and Dentistry
Rutland Place
Charterhouse Square
London
EC1M 6BQ
United Kingdom
Study information
| Study design | Prospective randomised single-centre double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A randomised, double-blind, placebo-controlled study investigating the effects of dietary nitrate on vascular function, platelet reactivity and restenosis in stable angina |
| Study acronym | NITRATE-OCT |
| Study objectives | The aim of this study is to investigate whether dietary nitrate might be useful in preventing restenosis in patients who have undergone elective angioplasty. |
| Ethics approval(s) | City Road & Hampstead Research Ethics Committee, 22/05/2015, ref: 15/LO/055 |
| Health condition(s) or problem(s) studied | Topic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Cardiovascular Prevention |
| Intervention | Participants are randomly allocated to one of two groups: Group 1: Participants receive 70ml beetroot juice concentrate containing 4-5mmol nitrate to drink daily, starting one day after their angioplasty procedure for 6 months. Group 2: Participants receive 70ml beetroot juice which is nitrate-depleted to drink daily, starting one day after their angioplasty procedure for 6 months. |
| Intervention type | Other |
| Primary outcome measure | Late-lumen loss within the stent is measured using optical coherence tomography (OCT) at 6 months. |
| Secondary outcome measures | 1. Improvement in endothelial function assessed by flow-mediated dilatation of the brachial artery at baseline and 6 months 2. Reduction in target vessel revascularisation (TVR), restenosis rate (diameter >50%) and in-segment late loss is measured using angiography at 6 months (+/- 1 month) 3. Reduction in major adverse cardiac events (i.e. MI, death, CVA, TVR) is measured using via a telephone call at 6, 12 and 24 months 4. Reduction in plaque size as assessed using OCT at 6 months (+/- 1 month) 5. Reduction in inflammatory markers and changes in plasma xanthine oxidase activity, hsCRP and IL-6 is measured using ELISAs at baseline, 6 and 12 months 6. Reduction in platelet count is measured using a blood test at baseline, 6 months and 12 months |
| Overall study start date | 02/11/2015 |
| Completion date | 02/04/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 246; UK Sample Size: 246 |
| Key inclusion criteria | 1. Aged between 18 and 85 2. Able and willing to provide informed consent 3. Patients undergoing successful PCI procedure 4. Patients with stable angina diagnosed by a cardiologist on optimal medical therapy, undergoing an angioplasty to treat residual symptoms |
| Key exclusion criteria | 1. Unstable ischaemic heart disease, with an episode of chest pain less than 24 hours 2. In patients who have had previous coronary artery bypass surgery (CABG), if they are undergoing angioplasty within a non-native vessel 3. Patients undergoing angioplasty with a bio-absorbable stent 4. Current diagnosis of or treatment for malignancy, other than nonmelanoma skin cancer 5. Current lifethreatening condition other than vascular disease that may prevent a subject completing the study 6. Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication 7. Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject’s unwillingness to comply with all study related procedures) 8. Severe acute infection, or significant trauma (burns, fractures) 9. Pregnancy (tested by urine HcG measurement) 10. History of alcohol or drug abuse within the past 6 months 11. A history of heart failure NYHA class 34 or severe LV dysfunction LVEF<30% regardless of symptom status 12. Systemic autoimmune disease such as rheumatoid arthritis, connective tissue disease, or other conditions known to be associated with chronic inflammation such as inflammatory bowel disease 13. Patients who have donated > 500mls blood within 56 days prior to study medication administration 14. Anaemia with Hb <10g/dl, or any other known blood disorder or significant illness that may affect platelet function, and coagulation 15. A history of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody or other chronic hepatic disorder) or HIV 16. Abnormal liver function due to acute or chronic liver conditions 3 x upper limit of normal at screening 17. Renal impairment with creatinine clearance (eGFR) of 30ml/min at screening 18. If patients are on mouthwash, they must be willing to stop using this at least 1 week before the start of the study and throughout the duration that they are involved within the study |
| Date of first enrolment | 02/11/2015 |
| Date of final enrolment | 02/04/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Queen Mary University of London
Charterhouse Square
London
EC1M 6BQ
United Kingdom
Sponsor information
Hospital/treatment centre
Research & Development Office
Queen Mary University of London
Barts & London School of Medicine
The QMI building
5 Walden Street
London
E1 2EF
England
United Kingdom
"ROR" |
https://ror.org/026zzn846 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | All relevant data from this study will be submitted to peer review journals for publication following the end of the study. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 20/12/2016 | 10/04/2019 | Yes | No |
Editorial Notes
13/05/2021: The intention to publish date has been changed from 01/08/2018 to 31/12/2021.
10/04/2019: Publication reference added.
