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

NCT03658174 | Completed

• 2 other identifiers: 0675Edge ID 108647
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Arrhythmia

Keywords

Nitrate

Outcome Measures

Primary Outcomes (4)

• Change in heart rate variability (HRV) from baseline

  Measure of autonomic function

  4 weeks and 8 weeks

• Change in QT variability index (QTVI) from baseline

  Marker of arrhythmia risk

  4 weeks and 8 weeks

• Change in Regional Restitution Instability Index (R2I2) from baseline

  Marker of ventricular arrhythmia and sudden cardiac death risk

  4 weeks and 8 weeks

• Change in Peak Electrocardiogram Restitution Slope (PERS) from baseline

  Marker of ventricular arrhythmia and sudden cardiac death risk

  4 weeks and 8 weeks

Secondary Outcomes (6)

• Change in left ventricular function from baseline

  4 weeks and 8 weeks

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

  4 weeks and 8 weeks

• Change in total exercise time on cardiopulmonary exercise test from baseline

  4 weeks and 8 weeks

• Change in the total score on the Minnesota Living With Heart Failure Quality of Life Questionnaire from baseline

  4 weeks and 8 weeks

• Participant compliance with dietary supplement

  4 weeks and 8 weeks

Study Arms (2)

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.

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.

Dietary Supplement: Nitrate-free beetroot juice

Interventions

Nitrate-rich beetroot juice DIETARY_SUPPLEMENT

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

Nitrate-rich beetroot juice

Nitrate-free beetroot juice DIETARY_SUPPLEMENT

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

Also known as: placebo

Nitrate-free beetroot juice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Glenfield Hospital, University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andre Ng, MBChB, PhD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blind placebo controlled crossover study

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 5, 2018
• Study Start: August 30, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: May 3, 2021

Record last verified: 2021-04

Locations

GB (1)