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

Heart Failure Clinical Trial

— UNTRAP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03658174
• Other study ID #: 0675
• Secondary ID: Edge ID 108647
• Status: Completed
• Phase: N/A
• Start date: August 30, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2021
• Source: University of Leicester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arrhythmia
• Heart Failure

Intervention

Dietary Supplement:
• Nitrate-rich beetroot juice
70mls of concentrated beetroot juice containing approximately 5-6 mmol of inorganic nitrate
• Nitrate-free beetroot juice
70mls of concentrated beetroot juice that has been nitrate-depleted

Locations

Country	Name	City	State
United Kingdom	Glenfield Hospital, University Hospitals of Leicester NHS Trust	Leicester	Leicestershire

Sponsors (4)

Lead Sponsor	Collaborator
University of Leicester	Loughborough University, National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK, University Hospitals, Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in heart rate variability (HRV) from baseline	Measure of autonomic function	4 weeks and 8 weeks
Primary	Change in QT variability index (QTVI) from baseline	Marker of arrhythmia risk	4 weeks and 8 weeks
Primary	Change in Regional Restitution Instability Index (R2I2) from baseline	Marker of ventricular arrhythmia and sudden cardiac death risk	4 weeks and 8 weeks
Primary	Change in Peak Electrocardiogram Restitution Slope (PERS) from baseline	Marker of ventricular arrhythmia and sudden cardiac death risk	4 weeks and 8 weeks
Secondary	Change in left ventricular function from baseline	LVEF, volumes and filling pressure (E/e ratio)	4 weeks and 8 weeks
Secondary	Change in peak oxygen uptake (VO2max) on cardiopulmonary exercise test from baseline	Maximum oxygen uptake	4 weeks and 8 weeks
Secondary	Change in total exercise time on cardiopulmonary exercise test from baseline	Time to exhaustion on exercise test	4 weeks and 8 weeks
Secondary	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	4 weeks and 8 weeks
Secondary	Participant compliance with dietary supplement	Compliance as measured using supplement and food diary	4 weeks and 8 weeks
Secondary	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	4 weeks