DiNOmo-HF

See the poster: DiNOmo-HF Posters [PDF 942KB]

Long title: Investigation of Dietary Nitrate Optimisation by hyperuricaemia stratification in Heart Failure: A randomised-control double-blind parallel two-limb study in patients with heart failure with reduced ejection fraction and NYHA II-III symptoms

Short Title: DiNOmo-HF

Sponsor: Queen Mary University of London

Funder: The Derek Willoughby Fund for Inflammatory Research and Barts Charity

Chief Investigator: Prof Amrita Ahluwalia, Professor of Vascular Pharmacology, Dean for Research, Queen Mary University of London

Co-investigators: Dr Simon Woldman, Barts Heart Centre; Dr Ceri Davies, Royal London Hospital; Dr Sanjeev Bhattacharyya Barts Heart Centre; Dr Charlotte Manisty, Barts Heart Centre; Dr Shanti Velmurugan, Barts Heart Centre

Contact: c.primus@qmul.ac.uk

Registration: https://clinicaltrials.gov/study/NCT03511248

Study Design: A Phase II, double-blind, placebo-controlled, randomised, multicentre trial of inorganic nitrate in the form of beetroot juice in patients with heart failure with reduced ejection fraction (HFrEF).

Objectives:

• To determine whether prolonged dietary nitrate ingestion reduces hyperuricaemia in patients with heart failure with reduced ejection fraction.
• To assess whether elevated XOR activity is associated with increased nitrite reductase potential.
• To evaluate the effects of sustained dietary nitrate intake on markers of cardiac function.

Number of Participants: 92

Study Duration: Active recruitment: 3 years, follow-up: 3 years

Location: William Harvey Heart Centre, William Harvey Research Institute, Queen Mary, University of London; Barts Heart Centre, St Bartholomew’s Hospital, London; Royal London Hospital, London; University College London Hospital (UCLH), London

Summary:

In the UK, around 900,000 people suffer with heart failure. Research groups are continuously working to identify new therapies that might improve overall health in patients with heart failure. These are in addition to the best medical treatment that your heart failure doctors prescribe you in clinic.

Nitric oxide is a substance normally produced by healthy blood vessels that plays an important part in maintaining blood vessel health. In patients with weak hearts, research has shown that the blood vessels are less able to make nitric oxide. Your doctors may well have used nitrates in tablet form to try and address this, with the aim of improving your symptoms and heart-related health. However, some patients develop tolerance to this type of drug and it does not address the underlying problem with the blood vessels themselves.

We know that diets rich in fruit and vegetables reduce the risk of blood vessel related disease, including heart attacks and stroke. Many vegetables, particularly green leafy vegetables and beetroot, are rich sources of dietary nitrate. Our recent research has shown that consuming this inorganic dietary nitrate results in more nitric oxide being produced in the body. This has been shown to be safe in healthy volunteers, as well as having benefit in patients with high blood pressure, high cholesterol and those having heart attacks.

The DiNOmo-HF study investigated whether dietary nitrate supplementation, in the form of beetroot juice, could improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), particularly those with high uric acid levels (hyperuricaemia). The study aimed to determine if nitrate supplementation could provide dual benefits: increasing nitric oxide levels while simultaneously reducing oxidative stress and uric acid levels through the enzyme xanthine oxidoreductase.

The trial was a randomised, double-blind, placebo-controlled study, where 92 patients were assigned to receive either nitrate-rich beetroot juice or nitrate-depleted beetroot juice (placebo) for 12 weeks. Participants were monitored for changes in hyperuricaemia, cardiac function, oxidative stress markers, and quality of life.

Key assessments included echocardiography, blood tests for nitrate and nitrite levels, oxidative stress markers, and a 6-minute walk test. The study also explored whether patients with high uric acid levels benefitted more from nitrate supplementation compared to those with normal levels.

The study aimed to show whether dietary nitrate could be an easy-to-administer, non-invasive therapy for heart failure patients. This research looked to explore the potential to introduce an affordable and widely available dietary intervention for a condition with high morbidity and limited treatment options.

The findings from this trial contributed to the growing understanding of nitric oxide pathways in heart failure and helped determine the feasibility of dietary nitrate as a therapeutic option.