Investigation of Dietary Nitrate Effects in Hypertension-induced Target Organ Damage

NCT03088514 | Completed Phase 2 DMC

• 1 other identifier: 10/H0703/98
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine whether dietary inorganic nitrate (in beetroot juice) is able to reduce overall thickening of the heart (left ventricular hypertrophy or LVH) and stiffness of the arteries when given to patients with persistently raised blood pressure (hypertension). Half the patients will receive the beetroot juice containing inorganic nitrate and half will receive beetroot juice from which the inorganic nitrate has been removed. The volunteers will take the juice every day for 4 months.

Conditions

Hypertension

Keywords

Hypertension; Left Ventricular Hypertrophy; Endothelial Dysfunction; Nitrate

Outcome Measures

Primary Outcomes (3)

• Left ventricular hypertrophy regression

  change in LV mass as assessed using cardiac magnetic resonance imaging

  4 months

• Pulse wave velocity

  non-invasive measures of arterial stiffness

  4 months

• Central blood pressure

  non-invasive measure of central blood pressure

  4 months

Secondary Outcomes (5)

• Flow mediated dilatation (FMD)

  4 months

• Brachial blood pressure

  4 months

• Change in plasma nitrate levels

  4 months

• Change in plasma nitrite levels

  4 months

• Change in nitric oxide activity (cGMP)

  4 months

Study Arms (4)

NITRATE-LVH intervention

EXPERIMENTAL

70ml of beetroot juice (approximately 6-8 mmol of inorganic nitrate) once a day for 4 months

Dietary Supplement: Beetroot juice

NITRATE-LVH placebo

PLACEBO COMPARATOR

70ml of beetroot juice (no inorganic nitrate) once a day for 4 months

Dietary Supplement: Beetroot juice

NITRATE-CBP intervention

EXPERIMENTAL

70ml of beetroot juice (approximately 6-8 mmol of inorganic nitrate) once a day for 4 month

Dietary Supplement: Beetroot juice

NITRATE-CBP placebo

PLACEBO COMPARATOR

70ml of beetroot juice (no inorganic nitrate) once a day for 4 months

Dietary Supplement: Beetroot juice

Interventions

Beetroot juice DIETARY_SUPPLEMENT

Beetroot juice (70ml daily) with or without inorganic nitrate

NITRATE-CBP intervention; NITRATE-CBP placebo; NITRATE-LVH intervention; NITRATE-LVH placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be enrolled following an informed consent. The subject will be able to understand and comply with protocol requirements, instructions and protocol restrictions.
• Aged 18-80 years.
• The study subjects will be hypertensives with evidence of difficulty treating to target BP (daytime ABPM 135-170/85-105 mmHg) on 1 or more antihypertensive agents, with insufficient efficacy or intolerance of medications.
• For NITRATE LVH, echocardiographic evidence of LV hypertrophy (LV mass indexed to body surface area (BSA); males \>115g/m2; females \>95 g/m2).
• Patients will have been established on an antihypertensive treatment regime for at least 1 month by the time of participation in the study and will not require changes in pharmacological intervention for the duration of the trial.

You may not qualify if:

• History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders.
• History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, 3x above the upper limit of normal or bilirubin 1.5x above the upper limit of normal at screening.
• Renal impairment with creatinine clearance (eGFR) of \<50 ml/min at screening.
• Patients with diabetes mellitus, defined by previous history of diabetes or HbA1c \>6.5% (\>48 mmol/mol) at screening.
• Subjects with LDLc, \>7.5 mmol/l. TG level \>10mmol/l.
• History of heart failure defined as NYHA class II - IV or those with known LV dysfunction (EF\<40%) regardless of symptomatic status
• History of malignancy within the past 5 years, other than non-melanoma skin cancer.
• Current life-threatening condition other than vascular disease (e.g. very severe chronic airways disease, HIV positive, life-threatening arrhythmias) that may prevent a subject from completing the study.
• Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• Subjects who will commence or who are likely to commence regular treatment with non-steroidal anti-inflammatory drugs (NSAIDs) (other than aspirin), from screening until study completion.
• Any non-stable dosing of ongoing medication regimens throughout the study trial.
• Drug abuse within the past 6 months.
• 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.
• 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).
• Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).

Sponsors & Collaborators

• Queen Mary University of London: lead
• Barts & The London NHS Trust: collaborator

Study Sites (1)

Queen Mary University of London

London, United Kingdom

Location

Related Publications (2)

• Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension. 2015 Feb;65(2):320-7. doi: 10.1161/HYPERTENSIONAHA.114.04675. Epub 2014 Nov 24.

  PMID: 25421976 BACKGROUND

• Lau CWZ, Hamers AJP, Rathod KS, Shabbir A, Cooper J, Primus CP, Davies C, Mathur A, Moon JC, Kapil V, Ahluwalia A. Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK. BMJ Open. 2020 Jan 21;10(1):e034399. doi: 10.1136/bmjopen-2019-034399.

  PMID: 31969369 DERIVED

MeSH Terms

Conditions

Hypertension; Hypertrophy, Left Ventricular

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cardiomegaly; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Amrita Ahulwalia, BSc PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Vascular Pharmacology

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 23, 2017
• Study Start: March 23, 2017
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

GB (1)