HypertensionPhase 2NITRATE-TODNCT03088514
Investigation of Dietary Nitrate Effects in Hypertension-induced Target Organ Damage
A Phase 2 study testing Beetroot juice in people with Hypertension, run by Queen Mary University of London at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Beetroot juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 149 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Mar 2017to 15 Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Unless specified, a subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 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.
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- 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).
- Subjects with any acute infection, or recent systemic (oral or IV) antibiotics within 1 month of screening, or significant trauma (burns, fractures).
- Subjects who have donated more than 500 mL of blood within 56 days prior to the study medication administration.
- Self reported use of anti-microbial mouthwash or tongue scrapes.
- Concomitant xanthine oxidase inhibitors (such as allopurinol).
- Known history of significant claustrophobia, previous intolerance of CMR imaging or known (or suspected) incompatible metallic implant.
- Pregnancy.
- Allergy to gadolinium-based contrast agents used for CMR.
- Patients with known LVH caused by another established pathology diagnosed prior to or at screening e.g. severe aortic stenosis, hypertrophic cardiomyopathy, amyloidosis and Fabry's disease.
- Exceptions to the exclusion criteria:
- For criteria 18, patients can enter the trial if they discontinue the use of anti-microbial mouthwash for the duration of the clinical trial.
- nCriteria 20 and 22 do not apply to participants who will not have a CMR scan in the NITRATE-CBP arm
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
In hypertension persistent raised blood pressure (BP) is associated with endothelial dysfunction, arterial stiffness and left ventricular (LV) remodeling that are key phenomena associated with the pathogenesis and complications of hypertension.
One of the main substances that the healthy endothelium produces that is responsible for maintaining the patency of blood vessels is nitric oxide (NO). In hypertension, one of the key pathogenic effects is the dysfunction of the endothelium characterized by a decrease in ability to generate nitric oxide (NO). Previous studies have shown that dietary inorganic nitrate supplementation lowers blood pressure (Kapil et al. 2015), however, whether this approach might also improve endothelial function and LV remodeling is unknown. The effects of inorganic nitrate are due to its conversion in the body to inorganic nitrite and thereafter to NO.
This study will assess the effects of dietary inorganic nitrate on LVH using cardiac magnetic resonance imaging (NITRATE-LVH arm). In addition, the effects of dietary inorganic nitrate on central aortic blood pressure, arterial stiffness using pulse wave velocity and endothelial function using flow mediated dilatation will be evaluated (NITRATE-CBP arm).
- Conditions
- Hypertension
- Being tested
- Beetroot juice
- Keywords
- Hypertension, Left Ventricular Hypertrophy, Endothelial Dysfunction, Nitrate
- Medical subject headings
- Hypertension, Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beetroot juiceDietary supplement
Beetroot juice (70ml daily) with or without inorganic nitrate
| Study group | Role | What they receive |
|---|---|---|
| NITRATE-LVH intervention | Experimental | 70ml of beetroot juice (approximately 6-8 mmol of inorganic nitrate) once a day for 4 months Receives: Dietary Supplement: Beetroot juice |
| NITRATE-LVH placebo | Placebo comparator | 70ml of beetroot juice (no inorganic nitrate) once a day for 4 months Receives: 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 Receives: Dietary Supplement: Beetroot juice |
| NITRATE-CBP placebo | Placebo comparator | 70ml of beetroot juice (no inorganic nitrate) once a day for 4 months Receives: Dietary Supplement: Beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular hypertrophy regression
change in LV mass as assessed using cardiac magnetic resonance imaging
Measured: 4 months
Pulse wave velocity
non-invasive measures of arterial stiffness
Measured: 4 months
Central blood pressure
non-invasive measure of central blood pressure
Measured: 4 months
Secondary outcomes (5)
Flow mediated dilatation (FMD)
non-invasive measure of endothelial function using ultrasound
Measured: 4 months
Brachial blood pressure
brachial blood pressure
Measured: 4 months
Change in plasma nitrate levels
assessed by chemiluminescence
Measured: 4 months
Change in plasma nitrite levels
assessed by chemiluminescence
Measured: 4 months
Change in nitric oxide activity (cGMP)
nitric oxide activity measured by determining plasma concentrations of cyclic guanosine monophosphate (cGMP)
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start23 Mar 2017
- Primary completion15 Nov 2023
- Study completion15 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Barts & The London NHS Trust
- Responsible party
- Principal investigator, Amrita Ahluwalia, Queen Mary University of London
- Investigators
- Amrita Ahulwalia, BSc PhD, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03088514
- Sponsor's protocol ID
- 10/H0703/98
- Acronym
- NITRATE-TOD
- Status last verified
- Feb 2024
- First submitted
- 9 Mar 2017
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25421976Lau 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.
PubMed 31969369
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Dietary Nitrate Effects in Hypertension-induced Target Organ Damage
- ClinicalTrials.gov ID
- NCT03088514
- Acronym / sponsor ID
- NITRATE-TOD / 10/H0703/98
- Conditions
- Hypertension
- Keywords
- Hypertension, Left Ventricular Hypertrophy, Endothelial Dysfunction, Nitrate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Barts & The London NHS Trust
- Study start
- 23 Mar 2017 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 23 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In hypertension persistent raised blood pressure (BP) is associated with endothelial dysfunction, arterial stiffness and left ventricular (LV) remodeling that are key phenomena associated with the pathogenesis and complications of hypertension.
One of the main substances that the healthy endothelium produces that is responsible for maintaining the patency of blood vessels is nitric oxide (NO). In hypertension, one of the key pathogenic effects is the dysfunction of the endothelium characterized by a decrease in ability to generate nitric oxide (NO). Previous studies have shown that dietary inorganic nitrate supplementation lowers blood pressure (Kapil et al. 2015), however, whether this approach might also improve endothelial function and LV remodeling is unknown. The effects of inorganic nitrate are due to its conversion in the body to inorganic nitrite and thereafter to NO.
This study will assess the effects of dietary inorganic nitrate on LVH using cardiac magnetic resonance imaging (NITRATE-LVH arm). In addition, the effects of dietary inorganic nitrate on central aortic blood pressure, arterial stiffness using pulse wave velocity and endothelial function using flow mediated dilatation will be evaluated (NITRATE-CBP arm).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NITRATE-LVH intervention | Experimental | Dietary Supplement: Beetroot juice70ml of beetroot juice (approximately 6-8 mmol of inorganic nitrate) once a day for 4 months |
| NITRATE-LVH placebo | Placebo comparator | Dietary Supplement: Beetroot juice70ml of beetroot juice (no inorganic nitrate) once a day for 4 months |
| NITRATE-CBP intervention | Experimental | Dietary Supplement: Beetroot juice70ml of beetroot juice (approximately 6-8 mmol of inorganic nitrate) once a day for 4 month |
| NITRATE-CBP placebo | Placebo comparator | Dietary Supplement: Beetroot juice70ml of beetroot juice (no inorganic nitrate) once a day for 4 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (27 listed)
- Unless specified, a subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beetroot juiceBeetroot juice (70ml daily) with or without inorganic nitrate | Dietary supplement | NITRATE-CBP intervention, NITRATE-CBP placebo, NITRATE-LVH intervention, NITRATE-LVH placebo |
Primary outcome
Left ventricular hypertrophy regression
Time frame: 4 months
change in LV mass as assessed using cardiac magnetic resonance imaging
Pulse wave velocity
Time frame: 4 months
non-invasive measures of arterial stiffness
Central blood pressure
Time frame: 4 months
non-invasive measure of central blood pressure
5 secondary outcomes
Flow mediated dilatation (FMD)
Time frame: 4 months
Brachial blood pressure
Time frame: 4 months
Change in plasma nitrate levels
Time frame: 4 months
Change in plasma nitrite levels
Time frame: 4 months
Change in nitric oxide activity (cGMP)
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Background: PubMed 25421976Kapil 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.
- Derived from this study: PubMed 31969369Lau 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amrita Ahulwalia, BSc PhD principal investigator
Queen Mary University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Beetroot juice in people with Hypertension, run by Queen Mary University of London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular hypertrophy regression (time frame: 4 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03088514, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.