Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Background and study aims
Nitrate is a chemical which plays an important part in regulating blood pressure and blood flow. Naturally, it is found in green leady vegetables and beetroot, although inorganic (man-made) supplements are becoming more common. Studies have shown that increased dietary intake of nitrates could prove to be beneficial for cardiovascular health (heart and blood vessels). In the body, nitrates are used by the cells that line the walls of blood vessels to produce the chemical nitric oxide (NO). NO causes the veins and arteries in the body to dilate, helping oxygen-rich blood to circulate around the body and to the heart. As more oxygen is carried around the body, the heart does not need to work as hard, which is particularly advantageous if someone is suffering from heart disease. Chronic heart failure (CHF) is a long-term condition where the heart has become weakened and isn’t able to pump blood around the body effectively. The aim of this study is to find out whether giving people suffering from CHF inorganic nitrate supplements could help to improve their condition.

Who can participate?
Adults who suffer from stable chronic (long-term) heart failure.

What does the study involve?
Participants are randomly allocated to one of two groups. Participants in the first group are given capsules containing inorganic sodium nitrate to take orally (by mouth) every day for 2 months. Participants in the second group are identical looking capsules containing a placebo (dummy) every day for 2 months. At the start of the study and then again after 1 week and 2 months, participants in both groups have the level of nitrate in their blood measured. Participants also complete questionnaires and physical tests to measure how well their heart is working when they exercise.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Norfolk and Norwich University Hospital NHS Trust (UK)

When is the study starting and how long is it expected to run for?
April 2016 to April 2019

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
Professor Michael Frenneaux

Trial website

Contact information



Primary contact

Prof Michael Frenneaux


Contact details

University of Aberdeen
Polwarth Building
AB25 2ZD
United Kingdom

Additional identifiers

EudraCT number

2012-000788-26 number

Protocol/serial number


Study information

Scientific title

The effects of inorganic nitrite on cardiac and skeletal muscle: Physiology, pharmacology and therapeutic potential in patients with chronic heart failure


Study hypothesis

Oral inorganic sodium nitrate supplementation will increase plasma levels of nitrite which will improve cardiac function and exercise capacity in association with an improvement in cardiac energy status compared to placebo.

Ethics approval

Scotland A Research Ethics Committee, 08/05/2012, ref: 12/SS/0037

Study design

Single-centre randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Topic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Heart Failure


Participants are randomly allocated to one of two groups.

Intervention group: Participants asked to take 7mmol inorganic sodium nitrate orally for two months
Control group: Participants asked to take an identical placebo orally for two months

Intervention type



Phase II

Drug names

Primary outcome measure

Peak VO2O2 consumption/workload relation during submaximal exercise at baseline and 2 months.

Secondary outcome measures

1. Cardiac and skeletal muscle energetic status is measured using an MRI at baseline and 2 months
2. Change in peak VO2 on exercise testing is measured after 1 week of treatment
3. Fasting plasma glucose and insulin (HOMA), high sensitivity CRP is measured at baseline, 1 week and 2 months
4. Quality of life is measured using the Minnesota Living with Heart Failure Questionnaire score at baseline and 2 months
5. Nitrate/nitrite/nitroso-species levels, conjugated nitro-fatty acid levels are measured at baseline, 1 week and 2 months
6. Oxygen uptake/workload relation on exercise testing is measured at baseline, 1 week and 2 months
7. Parameters of diastolic and systolic function on transthoracic echocardiogram are measured at baseline and 2 months
8. Plasma N-terminal Pro BNP are measured at baseline, 1 week and 2 months
9. Six minute hall-walk distance is measured at baseline and 2 months
10. Skeletal muscle proteomics on skeletal muscle biopsy is measured at baseline and 2 months

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Aged 18 years or over
2. Patients who suffer from symptomatic but stable chronic heart failure despite maximal tolerated contemporary medication, of non-ischaemic aetiology, in sinus rhythm

Participant type


Age group




Target number of participants

Planned Sample Size: 56; UK Sample Size: 56; Description: We will aim for a final cohort of 56 patients who complete the study for the Primary Endpoint

Participant exclusion criteria

1. Have been hospitalised for decompensated heart failure within the past three months.
2. Contra-indications for undergoing MRI.
3. Known G6PD deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent
4. Female subjects of childbearing potential
5. Valvular heart disease of moderate severity or greater
6. Predisposed to acute on chronic limb ischemia

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital NHS Trust
Colney Lane Colney
United Kingdom

Sponsor information


Norfolk and Norwich University Hospital NHS Trust

Sponsor details

Colney Lane
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

National government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

The following updates were made: 1. The recruitment end date was changed from 28/02/2018 to 01/02/2019 2. The overall trial end date was changed from 28/02/2018 to 01/04/2019