The effect of dietary nitrate supplementation on blood pressure and exercise capacity in people with COPD

ISRCTN ISRCTN47839214
DOI https://doi.org/10.1186/ISRCTN47839214
IRAS number 271589
Secondary identifying numbers IRAS: 271589
Submission date
30/10/2019
Registration date
01/11/2019
Last edited
16/06/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Dietary nitrate supplementation, in the form of beetroot juice, has a number of potentially advantageous effects in COPD. These include improving the response to pulmonary rehabilitation programme, making muscle contraction more efficient so it uses less oxygen, and improving how far people with low oxygen levels because of their lung disease can walk. Although COPD is a lung disease, people with the condition are at a higher risk of heart disease and stroke. There is also some evidence that beetroot juice can reduce blood pressure, but studies so far have been short term. A nutritional treatment that could produce a lasting reduction in blood pressure would be appealing, especially if it also improves people’s ability to exercise. The aim of this study is to investigate the prolonged treatment effects of daily beetroot juice on blood pressure in people with COPD. The researchers will also look at how far people can walk, make measurements of how well blood vessels function, and take blood samples to look at the mechanisms involved including how “sticky” platelets are. These are the cells in the blood that cause it to clot.

Who can participate?
Patients aged over 21 with COPD

What does the study involve?
Participants are randomly allocated to one of two groups. One group drinks a 70 ml beetroot juice “shot” each morning for three months. This contains nitrate, the active ingredient. The other group takes an identical juice drink which has had the nitrate removed. Which group participants are in is decided at random by a computer. Blood pressure is measured by participants at home for 4 days at the beginning and end of the study. In addition, the researchers measure how far people can walk, how well blood vessels work using a device that measures blood flow, and blood tests looking at nitrate levels and platelet function. They also collect mouth swabs to look at bacteria in the mouth to see if that changes with treatment.

What are the possible benefits and risks of participating?
If the study is positive this will help in the development of beetroot juice as a therapy for people with COPD and other long-term conditions. Participants in the study will be helping to advance understanding of processes involved in lung disease. If the treatment is effective participants in the active arm may benefit in terms of being able to walk further. Most people report that their urine goes orange or red because of the pigments in the beetroot juice.

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?
March 2019 to March 2022

Who is funding the study?
Saudi Arabia Cultural Bureau in London

Who is the main contact?
Mr Ali Alasmari
a.alasmari18@imperial.ac.uk

Contact information

Mr Ali Alasmari
Scientific

Royal Brompton Hospital
Fulham Rd
London
SW3 6NP
United Kingdom

Phone +44 (0)2073518029
Email a.alasmari18@imperial.ac.uk
Mr Ali Alasmari
Public

Royal Brompton Hospital
Fulham Rd
London
SW3 6NP
United Kingdom

Phone +44 (0)2073518029
Email a.alasmari18@imperial.ac.uk

Study information

Study designDouble-blind placebo-controlled parallel-group study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleOral Nitrate supplementation and Blood pressure in COPD – a randomised clinical trial
Study acronymON-BC
Study objectivesThe research question is whether, in people with stable COPD, oral dietary nitrate supplementation in the form of daily 70 ml beetroot shot compared to a placebo drink of nitrate-depleted beetroot juice, reduces blood pressure and improves exercise capacity and endothelial function over a three-month period.
Ethics approval(s)Approved 25/11/2019, London - West London & GTAC Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, UK; +44 (0)207 104 8007; 0207 104 8124; NRESCommittee.London-WestLondon@nhs.net), ref: 19/LO/1660
Health condition(s) or problem(s) studiedStable COPD
InterventionAllocation will be by computer-generated randomisation.

Active: 70 ml Beet It Stamina shot from James White Ltd (6.5 mmol Nitrate) once daily for three months
Placebo: 70 ml matched placebo shot with nitrate removed once daily for three months
Intervention typeSupplement
Primary outcome measureHome-monitored blood pressure measured using ambulatory blood pressure monitoring at baseline and 3 months
Secondary outcome measuresSecondary endpoints:
1. Exercise capacity measured using 6-minute walk test distance at baseline and 3 months
2. Health-related quality of life (HRQoL) assessed using the CAT score at baseline and 3 months

Exploratory endpoints measured at baseline and 3 months:
1. Endothelial function assessed using the Endopat score
2. Cardiac strain measured using Blood Brain Natriuretic Peptide levels (BNP)
3. Platelet activation measured using blood platelet-monocyte aggregates
4. Nitric oxide synthase activity assessed using plasma concentration of arginine/asymmetric dimethylarginine (ADMA)
5. Breath nitric oxide measured using fractional exhaled NO (FeNO)
6. Adequacy of supplementation measured using blood nitrate and nitrite levels
7. Nitrate metabolising oral bacteria measured using oral microbiome sampling
Overall study start date01/03/2019
Completion date01/03/2022

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants72
Total final enrolment81
Key inclusion criteria1. Adult patients (>21 years) with stable COPD GOLD I-IV
2. Established on stable pharmacotherapy for COPD
3. Systolic blood pressure >130 mmHg
Key exclusion criteria1. Unable to provide informed consent
2. AECOPD in the preceding month
3. Significant comorbidity limiting exercise tolerance
4. Significant comorbidity limiting life expectancy
5. Significant renal impairment (estimated glomerular filtration rate (eGFR) <30 ml.min1)
6. Use of >3 blood pressure lowering medications
7. Change in medication in the previous month
8. Oral nitrate medication
9. Current (in the last month) use of Beet Shots
Date of first enrolment01/12/2019
Date of final enrolment01/06/2021

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Royal Brompton and Harefield NHS Foundation Trust
Fulham Rd
London
SW3 6NP
United Kingdom

Sponsor information

Imperial College, London
University/education

Joint Research Compliance Office
Room 221 Level 2, Medical School Building
Norfolk Place
London
W2 1PG
England
United Kingdom

Phone +44 (0)20 75949480
Email k.boland@imperial.ac.uk
ROR logo "ROR" https://ror.org/041kmwe10

Funders

Funder type

Other

Saudi Arabia Cultural Bureau in London
Private sector organisation / Other non-profit organizations
Alternative name(s)
Royal Embassy of Saudi Arabia Cultural Bureau in London, Royal Embassy of Saudi Arabia - Cultural Bureau in London, Royal Embassy of Saudi Arabia Cultural Bureau, SACB
Location
United Kingdom

Results and Publications

Intention to publish date01/09/2022
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planThe results will be shared through presentation at conferences and publication in peer-reviewed medical journals.
IPD sharing planThe datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No
Protocol file version 2.0 24/06/2020 16/06/2025 No No
Results article 01/02/2024 16/06/2025 Yes No

Additional files

ISRCTN47839214_Protocol_v2.0_24June2020.pdf

Editorial Notes

16/06/2025: Publication reference and study protocol added.
07/03/2022: Total final enrolment added. The intention to publish date was changed from 01/06/2022 to 01/09/2022.
27/07/2020: The ethics approval was added.
31/10/2019: Trial's existence confirmed by ethics committee.