Investigating the Effects of Dietary Nitrate on Vascular Function, Platelet Reactivity and Restenosis in Stable Angina

NCT02529189 | Completed Phase 2 DMC

• 1 other identifier: 15/LO/0555
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Diseases

Keywords

Stable Angina; Angioplasty; Optical Coherence Tomography; Nitrate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• 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 target vessel revascularisation (TVR).

  6 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 in-segment late loss.

  6 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

Study Arms (2)

Nitrate-rich beetroot juice

ACTIVE COMPARATOR

70 ml of a beetroot juice concentrate containing \~5 mmol nitrate

Dietary Supplement: Beetroot Juice

Nitrate-deplete beetroot juice

PLACEBO COMPARATOR

70 ml of a beetroot juice concentrate that is nitrate-depleted

Dietary Supplement: Beetroot Juice

Interventions

Beetroot Juice DIETARY_SUPPLEMENT

70 ml of beetroot juice containing \~5 mmol of inorganic nitrate

Nitrate-rich beetroot juice

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Imperial College London: collaborator

Study Sites (1)

William Harvey Research Institute, Barts and The London School of Medicine

London, EC1M 6BQ, United Kingdom

Location

Related Publications (4)

• Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension. 2015 Feb;65(2):320-7. doi: 10.1161/HYPERTENSIONAHA.114.04675. Epub 2014 Nov 24.

  PMID: 25421976 BACKGROUND

• Ghosh SM, Kapil V, Fuentes-Calvo I, Bubb KJ, Pearl V, Milsom AB, Khambata R, Maleki-Toyserkani S, Yousuf M, Benjamin N, Webb AJ, Caulfield MJ, Hobbs AJ, Ahluwalia A. Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductase and translational potential. Hypertension. 2013 May;61(5):1091-102. doi: 10.1161/HYPERTENSIONAHA.111.00933. Epub 2013 Apr 15.

  PMID: 23589565 BACKGROUND

• Rathod KS, Mathur A, Shabbir A, Khambata RS, Lau C, Beirne AM, Chhetri I, Ono M, Belgaid DR, Massimo G, Ramasamy A, Tufaro V, Jain AK, Poulter N, Falaschetti E, Jones DA, Garcia-Garcia HM, Bourantas C, Learoyd A, Warren HR, Ahluwalia A. The NITRATE-OCT study-inorganic nitrate reduces in-stent restenosis in patients with stable coronary artery disease: a double-blind, randomised controlled trial. EClinicalMedicine. 2024 Oct 18;77:102885. doi: 10.1016/j.eclinm.2024.102885. eCollection 2024 Nov.

  PMID: 39469537 DERIVED

• Rathod KS, Jones DA, Van-Eijl TJ, Tsang H, Warren H, Hamshere SM, Kapil V, Jain AK, Deaner A, Poulter N, Caulfield MJ, Mathur A, Ahluwalia A. Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study. BMJ Open. 2016 Dec 20;6(12):e012728. doi: 10.1136/bmjopen-2016-012728.

  PMID: 27998900 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Angina, Stable

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Amrita Ahluwalia, PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2015
• First Posted: August 20, 2015
• Study Start: November 2, 2015
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

GB (1)