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 its 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
ON-EPIC Oral nitrate supplementation to enhance pulmonary rehabilitation in chronic obstructive pulmonary disease: a multi-centre, double blind, placebo-controlled, cross-over study
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)
NRES Committee London - London Bridge, 1/10/2014, Ref. 14/LO/1474
A multi-centre, double blind, placebo-controlled, cross-over study of the effect of nitrate supplementation on enhancing the effects of pulmonary rehabilitation.
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Chronic obstructive pulmonary disease (COPD)
Beetroot juice drink or matched nitrate-depleted placebo.
Primary outcome measures
Change in the incremental shuttle walking test (ISWT) distance.
Secondary outcome measures
1. Change in health status measured by the COPD assessment test score (CAT) and the Hospital Anxiety and Depression scale (HADs)
2. Change in fat free mass determined by bioelectrical impedance analysis
3. Flow mediated dilatation (FMD) will be increased after completion to PR
4. Change in blood plasma NO2- levels (a marker of NO production and availability) as a exploratory variable
All outcomes measured at 8 weeks
Overall trial start date
Overall trial end date
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
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)
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
Trial participating centre
Royal Brompton Hospital
Imperial College, London (UK)
c/o Christine Buicke
AHSC Joint Research Compliance Office
5th Floor Lab Block
JP Moulton Medical Foundation (UK)
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
Not provided at time of registration
Results - basic reporting