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

Sponsor
University of Leicester (Other)
Overall Status
Completed
CT.gov ID
NCT03658174
Collaborator
National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK (Other), Loughborough University (Other), University Hospitals, Leicester (Other)
20
Enrollment
1
Location
2
Arms
28.1
Actual Duration (Months)
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Nitrate-rich beetroot juice
  • Dietary Supplement: Nitrate-free beetroot juice
 N/A

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

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Double blind placebo controlled crossover studyDouble blind placebo controlled crossover study
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 30, 2018
Actual Primary Completion Date :
Dec 31, 2020
Actual Study Completion Date :
Dec 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Nitrate-rich beetroot juice

70mls of concentrated beetroot juice to be taken twice a day. This contains 5-6 mmol of inorganic nitrate.

Dietary Supplement: Nitrate-rich beetroot juice
70mls of concentrated beetroot juice containing approximately 5-6 mmol of inorganic nitrate
Placebo Comparator: Nitrate-free beetroot juice

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.

Dietary Supplement: Nitrate-free beetroot juice
70mls of concentrated beetroot juice that has been nitrate-depleted
Other Names:
  • placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in heart rate variability (HRV) from baseline [4 weeks and 8 weeks]

      Measure of autonomic function

    2. Change in QT variability index (QTVI) from baseline [4 weeks and 8 weeks]

      Marker of arrhythmia risk

    3. Change in Regional Restitution Instability Index (R2I2) from baseline [4 weeks and 8 weeks]

      Marker of ventricular arrhythmia and sudden cardiac death risk

    4. Change in Peak Electrocardiogram Restitution Slope (PERS) from baseline [4 weeks and 8 weeks]

      Marker of ventricular arrhythmia and sudden cardiac death risk

    Secondary Outcome Measures

    1. Change in left ventricular function from baseline [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 [4 weeks and 8 weeks]

      Maximum oxygen uptake

    3. Change in total exercise time on cardiopulmonary exercise test from baseline [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 [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 [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 [4 weeks]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Glenfield Hospital, University Hospitals of Leicester NHS Trust Leicester Leicestershire United Kingdom LE3 9QP

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Andre Ng, MBChB, PhD, University of Leicester

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Leicester
    ClinicalTrials.gov Identifier:
    NCT03658174
    Other Study ID Numbers:
    • 0675
    • Edge ID 108647
    First Posted:
    Sep 5, 2018
    Last Update Posted:
    May 3, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University of Leicester
    Nitrate
    Additional relevant MeSH terms:
    Heart Failure

    Study Results

    No Results Posted as of May 3, 2021