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 March 2017
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Professor Michael Frenneaux
Trial website
Additional identifiers
EudraCT number
2012-000788-26
ClinicalTrials.gov number
Protocol/serial number
13080
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
Acronym
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
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Heart Failure
Intervention
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
Other
Phase
Phase II
Drug names
Primary outcome measures
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
30/11/2015
Overall trial end date
28/02/2018
Reason abandoned
Eligibility
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
Patient
Age group
Adult
Gender
Both
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
30/11/2015
Recruitment end date
28/02/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Norfolk and Norwich University Hospital NHS Trust
Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom
Funders
Funder type
Research council
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
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
Results - basic reporting
Publication summary