Investigating the Effects of Dietary Nitrate on Vascular Function, Platelet Reactivity and Restenosis in Stable Angina
- Conditions
- Cardiovascular Diseases
- Interventions
- Dietary Supplement: Beetroot Juice
- Registration Number
- NCT02529189
- Lead Sponsor
- Queen Mary University of London
- Brief Summary
The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in patients with heart disease is stent implantation in the diseased coronary artery. Whilst this procedure has revolutionised treatment the incidence of secondary events remains a concern. These repeat events are due in part to continued enhanced platelet reactivity, endothelial dysfunction and a phenomenon called 'restenosis' i.e. the stent becomes blocked ultimately requiring another expensive and risky procedure. In this study it will be determined whether a once daily inorganic nitrate administration might favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis.
- Detailed Description
To address the aims a proof-of-concept study will be conducted to ascertain whether a dietary nitrate approach might prove useful adjunctive therapy improving vascular function in patients with stable angina post elective angioplasty.
Design: A prospective randomised, single-centre, double-blind, placebo-controlled trial
Setting: Patients with stable angina and single/multiple coronary artery stenosis undergoing elective percutaneous coronary intervention (PCI) who are haemodynamically stable (systolic BP\>100 mmHg). These patients will be recruited at The Barts Health Heart Centre, based at St. Bartholomew's Hospital. This is one of the biggest centres in the United Kingdom, serving a population of almost two million people from The City of London and The North East up to the M25 and is a 24/7 centre performing approximately 2000 non-primary angioplasties a year.
The study will take place in the Clinical Trials Unit, William Harvey Heart Centre.
Target population: A total of 300 patients (male and female, age 18-85) with stable angina as per requirements indicated above. Follow-up will take place in the Clinical Trials Unit, William Harvey Research Institute.
Treatment: Patients will be randomised (using an on line randomisation database) to receive 70 ml of a beetroot juice concentrate containing 4-5 mmol nitrate or nitrate-deplete placebo juice concentrate. This intervention will be taken by the patient daily from one day prior to re-establishment of flow with PCI and stent implantation.
Analysis: We will analyse the results based on an intention to treat analysis. We will also carry out further per protocol analyses and a subgroup analysis on patients who are on organic nitrates as part of their routine therapy and a comparison of DES (drug-eluting stents) versus BMS (bare-metal stents).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 300
- Patients with stable angina diagnosed by a cardiologist on optimal medical therapy undergoing angioplasty to treat residual symptoms.
- Aged 18-85
- Patients able and willing to give their written informed consent.
- Patients undergoing successful PCI procedure.
- Unstable ischaemic heart disease, with an episode of chest pain in less than 24 hours.
- Patients who have had previous coronary artery bypass surgery (CABG), if they are undergoing angioplasty within a non-native vessel.
- Patients undergoing angioplasty with a bio-absorbable stent.
- Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
- Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
- 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.
- 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).
- Severe acute infection, or significant trauma (burns, fractures).
- Pregnancy. This will be tested by urine human chorionic gonadotropin (hCG) measurement
- History of alcohol or drug abuse within the past 6 months.
- A history of heart failure New York Heart Association (NYHA) class 3-4 or severe left ventricular dysfunction (left ventricular ejection fraction of <30%) regardless of symptom status.
- 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.
- Patients who have donated > 500mls blood within 56 days prior to study medication administration.
- Anaemia with Hb <10g/dl, or any other known blood disorder or significant illness that may affect platelet function, and coagulation.
- A history of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody or other chronic hepatic disorder) or HIV.
- Abnormal liver function due to acute or chronic liver conditions 3 x upper limit of normal at screening.
- Renal impairment with creatinine clearance (eGFR) of 35ml/min at screening.
- 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 in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nitrate-rich beetroot juice Beetroot Juice 70 ml of a beetroot juice concentrate containing \~5 mmol nitrate Nitrate-deplete beetroot juice Beetroot Juice 70 ml of a beetroot juice concentrate that is nitrate-depleted
- Primary Outcome Measures
Name Time Method Difference between groups in In-stent late loss, where late loss is defined as the difference between the minimum luminal diameter (MLD). 6 months +/- 1 month post intervention
- Secondary Outcome Measures
Name Time Method Difference from baseline within the group and between groups in endothelial function assessed by flow-mediated dilatation of the brachial artery at 6 months compared to pre-procedure assessment. 6 months and 12 months post intervention Difference from baseline within the group and between groups in restenosis rate (diameter >50%). 6 months post intervention Difference from baseline within the group and between groups in plasma and erythrocyte nitrite reductase. 6 months and 12 months post intervention Difference from baseline within the group and between groups in target vessel revascularisation (TVR). 6 months post intervention Difference from baseline within the group and between groups in Interleukin-6 (IL-6). 6 months and 12 months post intervention Difference from baseline within the group and between groups in in-segment late loss. 6 months post intervention Difference from baseline within the group and between groups in changes in plasma xanthine oxidase activity. 6 months and 12 months post intervention Difference from baseline within the group and between groups high-sensitivity C-reactive protein (hsCRP). 6 months and 12 months post intervention Difference from baseline within the group and between groups in platelet activation (P-Selectin and platelet-monocyte aggregates). 6 months and 12 months post intervention Difference from baseline within the group and between groups in platelet aggregation ex vivo (ADP, collagen, arachidonic acid). 6 months and 12 months post intervention Difference from baseline between groups in major adverse cardiac events (i.e. Myocardial Infarction, death, Cerebrovascular Accident, Target Vascular Revascularisation). 6 months, 12 months and 24 months post intervention Difference from baseline within the group and between groups in inflammatory markers. 6 months and 12 months post intervention
Trial Locations
- Locations (1)
William Harvey Research Institute, Barts and The London School of Medicine
🇬🇧London, United Kingdom