Heart FailureUNTRAPNCT03658174
Upregulating the Nitric Oxide Pathway To Restore Autonomic Phenotype (UNTRAP).
A study testing Nitrate-rich beetroot juice and Nitrate-free beetroot juice in people with Heart Failure and Arrhythmia, run by University of Leicester at 1 site in United Kingdom.
Trial summary
Autonomic nervous system dysfunction is known to be associated with an increased risk of heart rhythm abnormalities and sudden cardiac death (SCD) in patients with chronic heart failure - a condition affecting millions of people worldwide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Arrhythmia
- What is being tested?
- Nitrate-rich beetroot juice and Nitrate-free beetroot juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 30 Aug 2018to 31 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female.
- Diagnosed with chronic heart failure - NYHA II-III
- Reduced heart rate variability
- Left ventricle ejection fraction (LVEF) of ≤40%
- Sinus rhythm on 12 lead ECG
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- Must have an adequate understanding of written and spoken English
- Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
- Able (in the Investigators opinion) and willing to comply with all study requirements
- Non-Invasive Programmed Stimulation (NIPS) Sub-Study Inclusion Criteria:
- Participant is willing and able to give informed consent for participation in the study
- Patients has a pre-existing ICD device with right ventricular apical lead
Who cannot join
- Myocardial infarction or coronary revascularization within the last 6 months before study enrolment
- NYHA class IV heart failure symptoms
- Persistent Atrial Fibrillation (AF)/Atrial flutter, or paroxysmal AF with frequent recent episodes of prolonged AF
- Patients taking any other nitrate containing medication or supplement (e.g. Isosorbide mononitrate, GTN)
- Patients taking proton pump inhibitors
- Severe pulmonary disease
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- Significant renal impairment (eGFR<15)
- Active cancer with life expectancy < 1year
- Patients with significant diabetic or other autonomic neuropathy
- Current or recent (within the last year) cigarette smokers
- Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
- Due to undergo any scheduled elective surgery or other procedures requiring general anaesthesia during the study.
- Participant who is inappropriate for placebo therapy
- Subjects who do not have an adequate understanding of written and spoken English
- Any other significant disease or disorder, which in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
- Participants who have participated in another research study involving an investigational product in the past 12 weeks
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Glenfield Hospital, University Hospitals of Leicester NHS Trust
Leicester, Leicestershire, LE3 9QP
About this study
Official title: Upregulating the Nitric Oxide Pathway To Restore Autonomic Phenotype (UNTRAP). A Double Blind Randomised First "Proof of Concept" Direct Translational Study to Explore the Effects of Dietary Nitrate Supplementation on Autonomic Function in Heart Failure Patients
Autonomic nervous system dysfunction is known to be associated with an increased risk of heart rhythm abnormalities and sudden cardiac death (SCD) in patients with chronic heart failure - a condition affecting millions of people worldwide. The nitric oxide pathway has been identified as being involved in mediating the effects of the autonomic nervous system on the heart. Recent studies have shown that dietary nitrates can increase the availability of nitric oxide in the body.
This study hopes to find out if dietary nitrate supplementation can help to improve cardiac and autonomic function in patients with heart failure and autonomic dysfunction and reduce the risk of arrhythmias.
Read the detailed description
20 participants enrolled at the University Hospitals of Leicester NHS Trust will be invited to take a beetroot juice supplement, which naturally contains a high concentration of nitrates, and a nitrate-free (placebo) beetroot supplement. In a double blind way, participants will be randomised to the order in which they receive the 2 treatments with crossover of the treatments. There will be a washout period between the two treatments.
In order to assess cardiac and autonomic function, and risk of heart rhythm abnormalities, tests will be carried out before and after each treatment period
Hypotheses:
- Nitrate supplementation reverses the autonomic dysfunction seen in Chronic Heart Failure (CHF)
- Markers of prognostic significance for predicting SCD, including QT variability index and cardiac restitution properties (R2I2, PERS), are normalised by nitrate supplementation in patients with CHF.
- Nitrate supplementation results in functional improvement in CHF patients.
- Conditions
- Heart Failure, Arrhythmia
- Being tested
- Nitrate-rich beetroot juice, Nitrate-free beetroot juice
- Keywords
- Nitrate
- Medical subject headings
- Heart Failure, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrate-rich beetroot juiceDietary supplement
70mls of concentrated beetroot juice containing approximately 5-6 mmol of inorganic nitrate
Nitrate-free beetroot juiceDietary supplement
Also called placebo
70mls of concentrated beetroot juice that has been nitrate-depleted
| Study group | Role | What they receive |
|---|---|---|
| Nitrate-rich beetroot juice | Active comparator | 70mls of concentrated beetroot juice to be taken twice a day. This contains 5-6 mmol of inorganic nitrate. Receives: Dietary Supplement: Nitrate-rich beetroot juice |
| Nitrate-free beetroot juice | Placebo comparator | 70mls of concentrated nitrate-free beetroot juice to be taken twice a day. This is an identical juice from which the nitrate has been removed using a standard anion exchange resin. Receives: Dietary Supplement: Nitrate-free beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heart rate variability (HRV) from baseline
Measure of autonomic function
Measured: 4 weeks and 8 weeks
Change in QT variability index (QTVI) from baseline
Marker of arrhythmia risk
Measured: 4 weeks and 8 weeks
Change in Regional Restitution Instability Index (R2I2) from baseline
Marker of ventricular arrhythmia and sudden cardiac death risk
Measured: 4 weeks and 8 weeks
Change in Peak Electrocardiogram Restitution Slope (PERS) from baseline
Marker of ventricular arrhythmia and sudden cardiac death risk
Measured: 4 weeks and 8 weeks
Secondary outcomes (6)
Change in left ventricular function from baseline
LVEF, volumes and filling pressure (E/e ratio)
Measured: 4 weeks and 8 weeks
Change in peak oxygen uptake (VO2max) on cardiopulmonary exercise test from baseline
Maximum oxygen uptake
Measured: 4 weeks and 8 weeks
Change in total exercise time on cardiopulmonary exercise test from baseline
Time to exhaustion on exercise test
Measured: 4 weeks and 8 weeks
Change in the total score on the Minnesota Living With Heart Failure Quality of Life Questionnaire from baseline
Measured using Minnesota Living With Heart Failure Quality of Life Questionnaire, with total score ranging from 0 to 105
Measured: 4 weeks and 8 weeks
Participant compliance with dietary supplement
Compliance as measured using supplement and food diary
Measured: 4 weeks and 8 weeks
Correlation between Non-Invasive Programmed Stimulation (NIPS) derived and exercise ECG derived R2I2 and PERS values
Assessment of the correlation between R2I2 and PERS values recorded using NIPS and exercise ECG
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2018
- Study start30 Aug 2018
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blind placebo controlled crossover study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK, Loughborough University, University Hospitals, Leicester
- Responsible party
- Sponsor
- Investigators
- Andre Ng, MBChB, PhD, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03658174
- Sponsor's protocol ID
- 0675
- Other IDs
- Edge ID 108647
- Acronym
- UNTRAP
- Status last verified
- Apr 2021
- First submitted
- 30 Aug 2018
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Upregulating the Nitric Oxide Pathway To Restore Autonomic Phenotype (UNTRAP). A Double Blind Randomised First "Proof of Concept" Direct Translational Study to Explore the Effects of Dietary Nitrate Supplementation on Autonomic Function in Heart Failure Patients
- ClinicalTrials.gov ID
- NCT03658174
- Acronym / sponsor ID
- UNTRAP / 0675
- Conditions
- Heart Failure, Arrhythmia
- Keywords
- Nitrate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Collaborators
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK, Loughborough University, University Hospitals, Leicester
- Study start
- 30 Aug 2018 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 5 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Autonomic nervous system dysfunction is known to be associated with an increased risk of heart rhythm abnormalities and sudden cardiac death (SCD) in patients with chronic heart failure - a condition affecting millions of people worldwide. The nitric oxide pathway has been identified as being involved in mediating the effects of the autonomic nervous system on the heart. Recent studies have shown that dietary nitrates can increase the availability of nitric oxide in the body.
This study hopes to find out if dietary nitrate supplementation can help to improve cardiac and autonomic function in patients with heart failure and autonomic dysfunction and reduce the risk of arrhythmias.
Detailed description
20 participants enrolled at the University Hospitals of Leicester NHS Trust will be invited to take a beetroot juice supplement, which naturally contains a high concentration of nitrates, and a nitrate-free (placebo) beetroot supplement. In a double blind way, participants will be randomised to the order in which they receive the 2 treatments with crossover of the treatments. There will be a washout period between the two treatments.
In order to assess cardiac and autonomic function, and risk of heart rhythm abnormalities, tests will be carried out before and after each treatment period
Hypotheses:
- Nitrate supplementation reverses the autonomic dysfunction seen in Chronic Heart Failure (CHF)
- Markers of prognostic significance for predicting SCD, including QT variability index and cardiac restitution properties (R2I2, PERS), are normalised by nitrate supplementation in patients with CHF.
- Nitrate supplementation results in functional improvement in CHF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind placebo controlled crossover study
| Arm | Type | Receives |
|---|---|---|
| Nitrate-rich beetroot juice | Active comparator | Dietary Supplement: Nitrate-rich beetroot juice70mls of concentrated beetroot juice to be taken twice a day. This contains 5-6 mmol of inorganic nitrate. |
| Nitrate-free beetroot juice | Placebo comparator | Dietary Supplement: Nitrate-free beetroot juice70mls of concentrated nitrate-free beetroot juice to be taken twice a day. This is an identical juice from which the nitrate has been removed using a standard anion exchange resin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female.
- Diagnosed with chronic heart failure - NYHA II-III
- Reduced heart rate variability
- Left ventricle ejection fraction (LVEF) of ≤40%
Key exclusion criteria (16 listed)
- Myocardial infarction or coronary revascularization within the last 6 months before study enrolment
- NYHA class IV heart failure symptoms
- Persistent Atrial Fibrillation (AF)/Atrial flutter, or paroxysmal AF with frequent recent episodes of prolonged AF
- Patients taking any other nitrate containing medication or supplement (e.g. Isosorbide mononitrate, GTN)
- Patients taking proton pump inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitrate-rich beetroot juice70mls of concentrated beetroot juice containing approximately 5-6 mmol of inorganic nitrate | Dietary supplement | Nitrate-rich beetroot juice |
| Nitrate-free beetroot juiceAlso: placebo70mls of concentrated beetroot juice that has been nitrate-depleted | Dietary supplement | Nitrate-free beetroot juice |
Primary outcome
Change in heart rate variability (HRV) from baseline
Time frame: 4 weeks and 8 weeks
Measure of autonomic function
Change in QT variability index (QTVI) from baseline
Time frame: 4 weeks and 8 weeks
Marker of arrhythmia risk
Change in Regional Restitution Instability Index (R2I2) from baseline
Time frame: 4 weeks and 8 weeks
Marker of ventricular arrhythmia and sudden cardiac death risk
Change in Peak Electrocardiogram Restitution Slope (PERS) from baseline
Time frame: 4 weeks and 8 weeks
Marker of ventricular arrhythmia and sudden cardiac death risk
6 secondary outcomes
Change in left ventricular function from baseline
Time frame: 4 weeks and 8 weeks
Change in peak oxygen uptake (VO2max) on cardiopulmonary exercise test from baseline
Time frame: 4 weeks and 8 weeks
Change in total exercise time on cardiopulmonary exercise test from baseline
Time frame: 4 weeks and 8 weeks
Change in the total score on the Minnesota Living With Heart Failure Quality of Life Questionnaire from baseline
Time frame: 4 weeks and 8 weeks
Participant compliance with dietary supplement
Time frame: 4 weeks and 8 weeks
Correlation between Non-Invasive Programmed Stimulation (NIPS) derived and exercise ECG derived R2I2 and PERS values
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andre Ng, MBChB, PhD principal investigator
University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitrate-rich beetroot juice and Nitrate-free beetroot juice in people with Heart Failure and Arrhythmia, run by University of Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in heart rate variability (HRV) from baseline (time frame: 4 weeks and 8 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.