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

NCT ID: NCT03658174

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-30
• Study Completion Date: 2020-12-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nitrate-rich beetroot juice

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

Group Type: ACTIVE_COMPARATOR

Nitrate-rich beetroot juice

Intervention Type: DIETARY_SUPPLEMENT

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

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.

Group Type: PLACEBO_COMPARATOR

Nitrate-free beetroot juice

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Nitrate-rich beetroot juice

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

Intervention Type: DIETARY_SUPPLEMENT

Nitrate-free beetroot juice

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

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

placebo

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK

OTHER

Sponsor Role: collaborator

Loughborough University

OTHER

Sponsor Role: collaborator

University Hospitals, Leicester

OTHER

Sponsor Role: collaborator

University of Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andre Ng, MBChB, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

Glenfield Hospital, University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, United Kingdom

Countries

United Kingdom

Other Identifiers

Edge ID 108647

Identifier Type: OTHER

Identifier Source: secondary_id

0675

Identifier Type: -

Identifier Source: org_study_id