Effects of inorganic nitrite on cardiac and skeletal muscle

ISRCTN ISRCTN16356908
DOI https://doi.org/10.1186/ISRCTN16356908
EudraCT/CTIS number 2012-000788-26
Secondary identifying numbers 13080
Submission date
02/12/2015
Registration date
02/12/2015
Last edited
12/03/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

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

Contact information

Prof Michael Frenneaux
Scientific

University of Aberdeen
Polwarth Building
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom

Study information

Study designSingle-centre randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Other
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleThe effects of inorganic nitrite on cardiac and skeletal muscle: Physiology, pharmacology and therapeutic potential in patients with chronic heart failure
Study objectivesOral 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(s)Scotland A Research Ethics Committee, 08/05/2012, ref: 12/SS/0037
Health condition(s) or problem(s) studiedTopic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Heart Failure
InterventionParticipants 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 typeOther
Primary outcome measurePeak VO2O2 consumption/workload relation during submaximal exercise at baseline and 2 months.
Secondary outcome measures1. 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 study start date30/11/2015
Completion date01/04/2019

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned 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
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment30/11/2015
Date of final enrolment01/02/2019

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Norfolk and Norwich University Hospital NHS Trust
Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom

Sponsor information

Norfolk and Norwich University Hospital NHS Trust
Hospital/treatment centre

Colney Lane
Colney
Norwich
NR4 7UY
England
United Kingdom

ROR logo "ROR" https://ror.org/01wspv808

Funders

Funder type

Research council

Medical Research Council
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No

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