Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Chronic obstructive pulmonary disease (COPD) is the name of a group of lung diseases (including emphysema and chronic bronchitis) that cause breathing difficulties due mostly to narrowing of the airways. It is most often caused by smoking and results in breathlessness, persistent coughing and recurrent chest infections. Even with excellent treatment, patients often find themselves significantly disabled by the disease. Pulmonary rehabilitation is a proven therapy for COPD where patients are placed on a 8 week programme which includes supervised exercise sessions and learning about their condition. However, places are limited and so it’s important to get as much benefit from them as possible. A number of studies have shown that increasing the amount of dietary nitrate in the diet makes exercise easier and less tiring. This is because dietary nitrates are converted into another compound called nitric oxide which widens blood vessels and reduces the amount of oxygen needed the muscles. Beetroot juice is a good source of dietary nitrate. We want to find out whether increasing the amount of nitrate in the diet (in the form of beetroot juice) can help to improve how patients respond to the pulmonary rehabilitation programme.

Who can participate?
Patients with COPD that may benefit from the pulmonary rehabilitation programme.

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given beetroot juice to drink. Those in group 2 are given a placebo (without nitrate). We then compare improvements in the amount of exercise they can do after they have all attended a pulmonary rehabilitation programme. This is tested with a shuttle walking test which measures how far and how fast each participants can walk without having to stop and rest. The participants are also asked to fill in questionnaires designed to assess their state of health. “Flow mediated dilatation” measurements, which see how responsive their blood vessels are also taken from some participants.

What are the possible benefits and risks of participating?
No risks are anticipated. Possible benefits include general improvement to health and being able to exercise for longer periods.

Where is the study run from?
Royal Brompton and Harefield NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
January 2015 to April 2018

Who is funding the study?
The JP Moulton Medical Foundation (UK)

Who is the main contact?
Dr Nicholas Hopkinson

Trial website

Contact information



Primary contact

Dr Nicholas Hopkinson


Contact details

Royal Brompton Hospital
Fulham Rd
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

ON-EPIC Oral nitrate supplementation to enhance pulmonary rehabilitation in chronic obstructive pulmonary disease: a multi-centre, double blind, placebo-controlled, cross-over study



Study hypothesis

The purpose of this study is to investigate the effects of administration of beetroot (BR) juice versus placebo beverage ingestion on exercise tolerance, health status, blood pressure, plasma NO2- levels, after attendance at a pulmonary rehabilitation.
The following hypotheses are to be tested:
1. BR would increase incremental shuttle walk test distance after completion of PR
2. BR would increase health related quality of life scores after completion of PR
3. BR would decrease fat mass after completion to PR
4. BR would increase plasma NO2- levels (a biomarker of NO production and availability)

Ethics approval

NRES Committee London - London Bridge, 1/10/2014, Ref. 14/LO/1474

Study design

Multi-centre double-blind placebo-controlled cross-over study

Primary study design


Secondary study design

Randomised cross over trial

Trial setting


Trial type


Patient information sheet

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


Chronic obstructive pulmonary disease (COPD)


Beetroot juice drink or matched nitrate-depleted placebo.

Intervention type



Not Applicable

Drug names

Primary outcome measure

Incremental shuttle walking test (ISWT) distance

Secondary outcome measures

All outcomes measured at 8 weeks:
1. Health status measured by the COPD assessment test score (CAT) and the Hospital Anxiety and Depression scale (HADs)
2. Fat free mass determined by bioelectrical impedance analysis
3. Flow mediated dilatation (FMD)

Removed 16/04/2018:
4. Blood plasma NO2 levels (a marker of NO production and availability) as an exploratory variable

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Patients will need to have a clinical and spirometric diagnosis of COPD, GOLD stage II-IV and with an MRC score of 3-5 or to be functionally limited

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Clinically unstable patients (within one month of exacerbation)
2. Within one month of completing pulmonary rehabilitation
3. Significant comorbidity limiting exercise tolerance
4. Significant renal impairment (estimated glomerular filtration rate (eGFR) <50 ml.min-1)
5. Hypotension (systolic blood pressure <100 mmHg)
6. Pregnancy
7. Use of nitrate based medication
8. Other reason for benefit from nitrate supplementation (ischaemic heart disease, peripheral arterial disease)
9. Use of long-term oxygen therapy

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Royal Brompton Hospital
United Kingdom

Sponsor information


Imperial College, London (UK)

Sponsor details

c/o Christine Buicke
AHSC Joint Research Compliance Office
5th Floor Lab Block
Imperial College
W6 8RF
United Kingdom

Sponsor type




Funder type

Research organisation

Funder name

JP Moulton Medical Foundation (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Publication is planned in a high-impact peer reviewed journal.

IPD sharing statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date


Participant level data


Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

16/04/2018: The secondary outcome measures were updated. 04/09/2017: The overall trial dates have been updated from 01/10/2014-30/09/2016 to 15/01/2015- 01/04/2018. The recruitment dates have been updated from 01/10/2014-30/09/2016 to 26/01/2015-01/11/2107. Intention to publish date has been added. Individual patient data sharing statement has been added.