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Completed

NCT Number: NCT03658174

Upregulating the Nitric Oxide Pathway To Restore Autonomic Phenotype (UNTRAP).

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Glenfield Hospital, University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE3 9QP, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Nitrate-rich beetroot Juice

Dietary Supplement

70mls of concentrated beetroot juice containing approximately 5-6 mmol of inorganic nitrate

Nitrate-free beetroot juice

Dietary Supplement

70mls of concentrated beetroot juice that has been nitrate-depleted

Other names: placebo

Primary outcomes

  1. Change in heart rate variability (HRV) from baseline

    Time frame: 4 weeks and 8 weeks

    Measure of autonomic function

  2. Change in QT variability index (QTVI) from baseline

    Time frame: 4 weeks and 8 weeks

    Marker of arrhythmia risk

  3. 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

  4. 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

Secondary outcomes

  1. Change in left ventricular function from baseline

    Time frame: 4 weeks and 8 weeks

    LVEF, volumes and filling pressure (E/e ratio)

  2. Change in peak oxygen uptake (VO2max) on cardiopulmonary exercise test from baseline

    Time frame: 4 weeks and 8 weeks

    Maximum oxygen uptake

  3. Change in total exercise time on cardiopulmonary exercise test from baseline

    Time frame: 4 weeks and 8 weeks

    Time to exhaustion on exercise test

  4. 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

    Measured using Minnesota Living With Heart Failure Quality of Life Questionnaire, with total score ranging from 0 to 105

  5. Participant compliance with dietary supplement

    Time frame: 4 weeks and 8 weeks

    Compliance as measured using supplement and food diary

  6. Correlation between Non-Invasive Programmed Stimulation (NIPS) derived and exercise ECG derived R2I2 and PERS values

    Time frame: 4 weeks

    Assessment of the correlation between R2I2 and PERS values recorded using NIPS and exercise ECG

Sponsors and collaborators

Lead sponsor

University of Leicester

Other

Collaborators

  • Loughborough University
  • National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK
  • University Hospitals, Leicester

Registry information

Official study 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

Acronym: UNTRAP

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Sep 5, 2018
Registry last updated
May 3, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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