COVID-19 studies are our top priority.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Date results information initially provided
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of dietary nitrate supplementation on brain blood vessel health
Scientific title
Effect of dietary nitrate supplementation on cerebrovascular health in high risk transient ischaemic attack (TIA) patients
Secondary ID [1] 288381 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transient ischaemic attack 297386 0
Condition category
Condition code
Stroke 297575 297575 0 0

Study type
Description of intervention(s) / exposure
7 day dietary sodium nitrate supplementation, 0.1mmol/kg/day (rounded to the nearest 60mg), administered in oral capsules (sodium nitrate, 60mg/capsule) across the meals (3 times daily). Adherence will be monitored by self-report, empty drug packet and assessment of pre and post blood plasma nitrate concentration.
Intervention code [1] 293687 0
Treatment: Other
Comparator / control treatment
TIA patients with 7 day placebo treatment containing sugar
healthy subjects with 7 day dietary nitrate supplementation and 7 day placebo treatment with a minimum 5 day washout period.
Control group

Primary outcome [1] 297122 0
Cerebral blood flow regulation using transcranial Doppler ultrasound.
Timepoint [1] 297122 0
Post 7 days of treatment
Primary outcome [2] 297132 0
cerebral tissue oxygenation using Near-infrared spectroscopy
Timepoint [2] 297132 0
Post 7 days of treatment
Secondary outcome [1] 320083 0
blood pressure control using finger plethysmography.
Timepoint [1] 320083 0
Post 7 days of treatment
Secondary outcome [2] 320118 0
Peripheral arterial stiffness using flow-mediated dilatation. Assessing using Duplex Doppler ultrasound.
Timepoint [2] 320118 0
post 7 days of treatment

Key inclusion criteria
Patient group
1) Those individuals aged 40-85 diagnosed as high risk TIA (with ABCD2 score greater than or equal to 4), after review by a specialist stroke physician
2) Those individuals living within Wellington City and the Greater Wellington region
Healthy group
1) Healthy individuals (age 20-85 years) of both sex, specifically:
2) Free of history of long-term disease
3) Not currently taking any medication that may influence measures in this study.
4) Those individuals living within Wellington City and the Greater Wellington region

Minimum age
20 Years
Maximum age
85 Years
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
Patient group
1) Those individuals requiring supplementary oxygen
2) Individuals with allergy to nitrates
3) Unstable cardiac conditions or angina
4) Uncontrolled diabetes mellitus
5) Major medical conditions
6) Significant cognitive impairment
7) Immobility

Healthy group
1) Very high (greater than 140/90) or very low (lower than 100/60) resting blood pressure
2) Previous history of stroke, brain surgery, or severe head trauma
3) Pregnancy

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
The TIA patient group will undergo a parallel design, whilst the healthy control group will be crossover design
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
One of the primary dependent variables of interest is cerebral blood flow regulation. The sample size estimate was based on published (Aamand et al 2013; 2014; Presley et al 2011) and unpublished pilot data, which has assessed the effects of dietary nitrate on cerebrovascular function. These were used to estimate a physiologically relevant improvement in cerebrovascular function of 16% between the two randomized groups. Assuming that dietary nitrate supplementation can improve cerebrovascular function by a similar extent, 17 TIA patients per group (34 TIA patients total) and 17 healthy controls would provide > 80% power to detect a moderate effect size that corresponds to a ~100% difference between treatment and placebo interventions, assuming a standard deviation of 0.65%/mmHg at a two-tailed significance level of 0.05.

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment outside Australia
Country [1] 7544 0
New Zealand
State/province [1] 7544 0
Wellington region

Funding & Sponsors
Funding source category [1] 292739 0
Name [1] 292739 0
New Zealand Heart Foundation
Address [1] 292739 0
PO Box 17-160 Greenlane, Auckland 1546
Country [1] 292739 0
New Zealand
Primary sponsor type
Mickey Fan
University of Otago
23A Mein Street
Wellington 6021
New Zealand
Secondary sponsor category [1] 291466 0
Name [1] 291466 0
University of Otago
Address [1] 291466 0
362 Leith St, North Dunedin, Dunedin 9016
Country [1] 291466 0
New Zealand

Ethics approval
Ethics application status
Ethics committee name [1] 294223 0
Health and Disability Ethics Committees
Ethics committee address [1] 294223 0
Ministry of Health
Freyberg building
20 Aitken Street
PO Box 5013
Wellington 6145
Ethics committee country [1] 294223 0
New Zealand
Date submitted for ethics approval [1] 294223 0
Approval date [1] 294223 0
Ethics approval number [1] 294223 0

Brief summary
Stroke is a leading cause of long-term disability in many countries, causing both physical and cognitive problems. Patients who have recently suffered a transient ischaemic attack (TIA) event are particularly at risk of stroke. This study will investigate if a nitrate supplement can improve cerebrovascular health and enhance recovery from a TIA event, possibly lower risk factors which may lead to a later stroke. In human studies, dietary nitrate supplementation has been shown to lower blood pressure. Since high blood pressure is one of the main causes of stroke, dietary nitrate supplementation may reduce the risk of stroke in patients with TIA. Improving our understanding of the impact of the dietary supplementation on the cerebrovascular health of TIA patients would be an important step towards finding better treatments for TIA patients in New Zealand and elsewhere.
We will test the hypothesis that dietary nitrate supplementation improves cerebrovascular health and blood pressure regulation in patients with TIA.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 62942 0
Dr Mickey Fan
Address 62942 0
University of Otago
23A Mein Street
Wellington 6021
Country 62942 0
New Zealand
Phone 62942 0
+64 4 918 5395
Fax 62942 0
Email 62942 0
Contact person for public queries
Name 62943 0
Dr Mickey Fan
Address 62943 0
Mickey Fan
University of Otago
23A Mein Street
Wellington 6021
Country 62943 0
New Zealand
Phone 62943 0
+64 4 918 5395
Fax 62943 0
Email 62943 0
Contact person for scientific queries
Name 62944 0
Dr Mickey Fan
Address 62944 0
Mickey Fan
University of Otago
23A Mein Street
Wellington 6021
Country 62944 0
New Zealand
Phone 62944 0
+64 4 918 5395
Fax 62944 0
Email 62944 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Journal publication details
Publication date and citation/details [1] 10113 0
Dietary nitrate reduces blood pressure and cerebral artery velocity fluctuations and improve cerebral autoregulation in transient ischemic attack patients. August 2020. Journal of Applied Physiology. DOI: 10.1152/japplphysiol.00160.2020
Attachments [1] 10113 0
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary
We found dietary nitrate supplementation reduced blood pressure and brain blood flow fluctuations and improved the relationship between blood pressure and brain blood flow in transient ischemic attack patients. Meanwhile, dietary nitrate had no effects on the brain blood vessels’ response to CO2. We attribute the improved brain blood flow stability to the improved myogenic control of blood pressure with dietary nitrate. Our findings indicate that dietary nitrate could be an effective strategy for stabilizing blood pressure and brain blood flow following transient ischemic attack.