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Trial record 9 of 528 for:    NITRATE ION

Effect of Dietary Nitrate Ingestion in Heart Failure (DiNOmo-HF)

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ClinicalTrials.gov Identifier: NCT03511248
Recruitment Status : Recruiting
First Posted : April 27, 2018
Last Update Posted : June 18, 2018
Sponsor:
Information provided by (Responsible Party):
Queen Mary University of London

Brief Summary:
This study evaluates the addition of inorganic dietary nitrate to the optimal treatment of patients diagnosed with heart failure with reduced ejection fraction. Some vegetables contain large amounts of inorganic nitrate, and research suggests that this nitrate has beneficial effects on the heart and blood vessels. We have shown in lab experiments that nitrate has positive effects on the heart. We wish to test whether dietary nitrate might be useful in halting deterioration and/or improving heart function in patients with heart failure, with a specific focus on a marker of poor outcome in heart failure: high uric acid levels. Half of the patients will receive nitrate-rich beetroot juice, and the other half a nitrate-deplete placebo beetroot juice.

Condition or disease Intervention/treatment Phase
Heart Failure Heart Failure, Systolic Dietary Supplement: Nitrate-rich Beetroot Juice Dietary Supplement: Nitrate-deplete Beetroot Juice Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised double-blind placebo-controlled parallel two-limb study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind study, with randomisation undertaken by Barts Cardiovascular Clinical Trials Unit
Primary Purpose: Treatment
Official Title: Investigation of Dietary Nitrate Optimisation by Hyperuricaemia Stratification in Heart Failure
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Nitrate-rich Beetroot Juice
Individuals will receive a once daily dose of dietary nitrate in the form of a beetroot juice concentrate (70mL) containing ~5-6mmol inorganic nitrate (James White Drinks, UK) for 12 +/- 2 weeks. This dose has been chosen due to several reports demonstrating efficacy in patients with cardiovascular disease.
Dietary Supplement: Nitrate-rich Beetroot Juice
The beetroot juice contains approximately 100kcal per 100mL of juice, equivalent to a glass of orange juice; the volume of juice per day for the study is 70mL. Volunteers will be informed that an average woman weighing 65kg should not consume more than 2000kcal per day, and an average man of 75kg not more than 2500kcal per day.

Placebo Comparator: Nitrate-deplete Beetroot Juice
The placebo control is an identical juice from which the nitrate anion has been removed using a standard anion exchange resin. Visually there is no detectable difference between the juices and previous spectral, ion concentration, sugar levels, ascorbate analysis and taste testing has confirmed no differences in colour and constituents. The process to extract nitrate from the juice is the same technique used to remove inorganic nitrate from general drinking water supplies, and has been approved for use by Ethics Committees. The nitrate-free juice is not considered a drug or medicine, and is classified as a foodstuff.
Dietary Supplement: Nitrate-deplete Beetroot Juice
The beetroot juice contains approximately 100kcal per 100mL of juice, equivalent to a glass of orange juice; the volume of juice per day for the study is 70mL. Volunteers will be informed that an average woman weighing 65kg should not consume more than 2000kcal per day, and an average man of 75kg not more than 2500kcal per day.
Other Name: Placebo




Primary Outcome Measures :
  1. Change in serum uric acid levels [ Time Frame: 12 +/- 2 weeks ]
    Uric acid is a prognostic marker in patients with heart failure. The intervention proposed acts on the enzyme, xanthine oxidoreductase (XOR), that produces uric acid. We will therefore measure the change in serum uric acid level from baseline to assess whether dietary nitrate treatment decreases hyperuricaemia. We will stratify uric acid levels and undertake analysis between strata.


Secondary Outcome Measures :
  1. Changes in plasma nitrate [ Time Frame: 12 +/- 2 weeks ]
    We will measure the change in nitrate levels in plasma using ozone chemiluminescence, which measures the consumed dose of inorganic nitrate consumed, as the first step in the enterosalivary circuit.

  2. Changes in plasma nitrite [ Time Frame: 12 +/- 2 weeks ]
    We will measure the change in nitrite levels in plasma using ozone chemiluminescence, measuring the conversion of nitrate to nitrite which the enzyme XOR uses to form the biologically active metabolite, nitric oxide.

  3. Changes in cGMP as a marker for Nitric Oxide [ Time Frame: 12 +/- 2 weeks ]
    We will measure the change in cGMP levels using an ELISA assay, as a stable and measurable surrogate of the biologically active product, nitric oxide.

  4. Changes in cardiac pump function [ Time Frame: 12 +/- 2 weeks ]
    Using cardiac magnetic resonance imaging (cardiac MRI), we will measure the change in left ventricular ejection fraction from baseline following intervention.


Other Outcome Measures:
  1. Changes in markers of oxidative stress: MDA [ Time Frame: 12 +/- 2 weeks ]
    Measured using ELISA and used collectively with oxidised LDL and TBAR assays to determine oxidative stress

  2. Changes in markers of oxidative stress: oxidised LDL [ Time Frame: 12 +/- 2 weeks ]
    Measured using ELISA and used collectively with MDA and TBAR assays to determine oxidative stress

  3. Changes in markers of oxidative stress: TBAR [ Time Frame: 12 +/- 2 weeks ]
    Measured using ELISA and used collectively with oxidised LDL and MDA assays to determine oxidative stress

  4. Measure of red blood cell XOR activity [ Time Frame: 12 +/- 2 weeks ]
    We will measure expression and activity of XOR by red blood cells, as a marker of both nitrite reductase capacity as well as hyperuricaemia.

  5. Changes in blood pressure [ Time Frame: 12 +/- 2 weeks ]
    Analysis of 24-hour blood pressure monitoring

  6. Change in NT-proBNP [ Time Frame: 12 +/- 2 weeks ]
    Analysis of this important natriuretic peptide

  7. Change in BNP [ Time Frame: 12 +/- 2 weeks ]
    Analysis of this important natriuretic peptide

  8. Change in high sensitivity C-Reactive Protein [ Time Frame: 12 +/- 2 weeks ]
    Analysis of the highly sensitive marker of inflammation

  9. Change in lipid levels (LDL, triglycerides, HDL, total cholesterol) [ Time Frame: 12 +/- 2 weeks ]
    Analysis of lipids

  10. Cardiac MRI analysis: ventricular function [ Time Frame: 12 +/- 2 weeks ]
    Measurement of cardiac ventricular function using cardiac MRI (ejection fraction)

  11. Cardiac MRI analysis: ventricular volumes [ Time Frame: 12 +/- 2 weeks ]
    Measurement of cardiac ventricular volumes using cardiac MRI

  12. Cardiac MRI analysis: pattern of scarring [ Time Frame: 12 +/- 2 weeks ]
    Assessment of heart failure aetiology as measured by late gadolinium enhancement on cardiac MRI

  13. Changes in resting cardiac electrical activity [ Time Frame: 12 +/- 2 weeks ]
    As determined by electrocardiogram analysis

  14. 6-minute Walk Test [ Time Frame: 12 +/- 2 weeks ]
    Functional assessment of exercise capacity

  15. Minnesota Living with Heart Failure Quality of Life Questionnaire [ Time Frame: 12 +/- 2 weeks ]
    Qualitative analysis of quality of life

  16. Stratification by Type II Diabetes Mellitus [ Time Frame: 12 +/- 2 weeks ]
    All results will be stratified by the pre-existing diagnosis of Type II Diabetes Mellitus to determine whether this additional cause of oxidative stress impacts on the ability of inorganic nitrate to recover function in patients with heart failure

  17. Evidence of active dental caries [ Time Frame: 12 +/- 2 weeks ]
    Pre-specified sub-group analyses by dental disease

  18. Measurement of methaemaglobinaemia [ Time Frame: 12 +/- 2 weeks ]
    Safety measure



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years
  2. Diagnosed with heart failure with reduced ejection fraction on the basis of:

    1. LVEF ≤40% as assessed by Echocardiography (or cardiac MRI)
    2. raised BNP and/or NT-proBNP levels placing patients in the "high risk" category, to ensure heart failure is the cause of symptoms (as per NICE Guidance and inclusion crieteria of the PARADIGM-HF Trial):

      • stable heart failure: NT-proBNP >600pg/mL and BNP >150pg/mL
      • hospitalisation within 12 months: NT-proBNP >400pg/mL and BNP >100pg/mL
  3. NYHA Class II-III symptoms
  4. On optimally-tolerated, stable (>12 weeks) prognostic medical therapy (beta-blocker, ACE-inhibitor or ARB, mineralocorticoid therapy if deemed necessary)
  5. No heart failure-related hospitalisation for >12 weeks
  6. Clinic systolic blood pressure ≥110mmHg
  7. Able and willing to give written informed consent

The intervention with dietary nitrate is intentionally designed to be in addition to the patient's own lifestyle. There will be no restrictions placed on diet, anti-oxidant supplements or prescription medications, other than those listed in the exclusion criteria below.

Exclusion Criteria:

  1. Use of anti-bacterial mouthwash or tongue scrapes (current or unwillingness to cease such mouthcare for at least one month prior to entering the study, and for the duration of the trial) as this interrupts the enterosalivary circuit and thus prevents the bioactivity of nitrate
  2. History of recurrent symptomatic gout or current treatment with xanthine oxidase inhibitors for hyperuricaemia
  3. Concomitant use of long acting organic nitrates or phosphodiesterase inhibitors (not including on an as required basis)
  4. Angina at CCS Class III/IV, requiring regular use of sublingual GTN (considered >twice/week), or awaiting revascularisation
  5. Renal failure with eGFR<30 at screening
  6. History of symptomatic renal stone disease
  7. Current life-threatening condition that might prevent a patient-subject completing the study
  8. Medical devices (including non-MRI conditional pacemakers and implantable cardiac defibrillators) or other conditions that preclude imaging with cardiac MRI
  9. Pregnancy
  10. Anaemia, defined as Haemaglobin <80g/L
  11. Subjects with any acute infection, or recent systemic antibiotics (oral or intravenous) within 3 months of screening, or significant trauma (burns, fractures)
  12. The subject has a three-month prior history of regular alcohol consumption exceeding an average weekly intake of > 28 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 21 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine
  13. Mobility thought to be restricted significantly by other illnesses apart from heart failure
  14. Any other subject whom the Investigator deems unsuitable for the study (e.g. due to other medical reasons, laboratory abnormalities, expected study medication noncompliance, or subject's unwillingness to comply with all study-related study procedures)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03511248


Contacts
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Contact: Prof Amrita Ahluwalia, BSc PhD 020 7882 8377 a.ahluwalia@qmul.ac.uk
Contact: Dr Christopher P Primus, MBBS BSc MRCP 020 7882 5720 c.primus@qmul.ac.uk

Locations
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United Kingdom
Queen Mary University of London Recruiting
London, United Kingdom
Contact: Prof Amrita Ahluwalia, BSc PhD       a.ahluwalia@qmul.ac.uk   
Contact: Dr Christopher P Primus, MBBS BSc MRCP       c.primus@qmul.ac.uk   
Principal Investigator: Amrita Ahulwalia, BSc PhD         
Sub-Investigator: Christopher P Primus, MBBS BSc MRCP         
Principal Investigator: Simon Woldman, MD FESC FRCP         
Principal Investigator: Ceri Davies, MD FRCP FESC         
Sub-Investigator: Charlotte Manisty, MBBS PhD MRCP         
Sub-Investigator: Shanti Velmurugan, MBBS PhD MRCP         
Sub-Investigator: Clement Lau, MBChB BMedSci MRCP         
Sub-Investigator: Krishnaraj Rathod, MBBS BMedSci MRCP         
Sponsors and Collaborators
Queen Mary University of London
Investigators
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Principal Investigator: Dr Simon Woldman, MD FRCP FESC Fellow of the Royal College of Physicians and Fellow of the European Society of Cardiology
Principal Investigator: Dr Ceri Davies, MD FRCP FESC Fellow of the Royal College of Physicians and Fellow of the European Society of Cardiology
Study Chair: Prof Amrita Ahluwalia, BSc PhD William Harvey Research Institute, Queen Mary University of London

Publications:

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Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT03511248     History of Changes
Other Study ID Numbers: 17/LO/1624
First Posted: April 27, 2018    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Not applicable - no plans to share IPD

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Queen Mary University of London:
Heart Failure
Heart Failure with Reduced Ejection Fraction
Nitric Oxide
Inorganic Nitrate
Additional relevant MeSH terms:
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Heart Failure
Heart Failure, Systolic
Heart Diseases
Cardiovascular Diseases