NitrateNCT06602921
The Effects of Nitrate, Caffeine, and Cold Exposure on Cardiovascular Function.
A study testing TruBeet inorganic beetroot juice, Caffeine and Cold pressor test in people with Nitrate and Caffeine, run by Loughborough University at 1 site in United Kingdom.
Trial summary
Dietary inorganic nitrate supplementation may have positive implications on cardiovascular function. The aim of this project is to determine if nitrate supplementation can attenuate the effects that caffeine and cold exposure have on the cardiovascular system. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Nitrate, Caffeine, Cold Exposure
- What is being tested?
- TruBeet inorganic beetroot juice, Caffeine and Cold pressor test
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Dec 2023to 1 Apr 2025
- Phase
- Interventional
- 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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Blood pressure < 130 mmHg systolic and < 85 mmHg diastolic. BMI between 18.5 and 29.9 kg/m2. Females must be naturally menstruating (regular length cycle and menses) or using a form of combined hormonal contraception (for at least 6 months).
Who cannot join
- Existing cardiovascular or metabolic conditions. Experience any adverse reactions to experimental procedures or supplements. Allergies to supplements or breakfast items. Involved in any other studies. Blood pressure > 130 mmHg systolic and > 85 mmHg diastolic.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Dietary Nitrate Supplementation Attenuate the Cardiovascular Strain Elicited by Caffeine and Cold Exposure in Healthy Individuals?
Dietary inorganic nitrate supplementation may have positive implications on cardiovascular function. The aim of this project is to determine if nitrate supplementation can attenuate the effects that caffeine and cold exposure have on the cardiovascular system.
Read the detailed description
Acute caffeine consumption and cold exposure elicit negative effects on the cardiovascular system. Humans are regularly exposed to such conditions of increased cardiovascular strain, which may lead to elevated chronic cardiovascular risk. On the other hand, dietary inorganic nitrate supplementation is well established to improve cardiovascular function in healthy individuals. Thus, acute nitrate supplementation may compensate for the negative effects that caffeine and the cold place on the cardiovascular system. These effects will be measured using peripheral blood pressure, pulse wave analysis, heart rate variability, forearm blood flow, flow mediated dilation, and blood and saliva markers.
- Conditions
- Nitrate, Caffeine, Cold Exposure
- Being tested
- TruBeet inorganic beetroot juice, Caffeine, Cold pressor test
- Keywords
- Cardiovascular Function, Flow mediated dilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TruBeet inorganic beetroot juiceDietary supplement
400 mg nitrate-rich beetroot powder, mixed with 300 mL water.
CaffeineDietary supplement
6 mg/kg caffeine powder in capsule form.
Cold pressor testOther
3 min cold pressor test using the left foot in cold water (0-2 degree).
| Study group | Role | What they receive |
|---|---|---|
| Nitrate, caffeine, and cold pressor test (CPT) | Experimental | All outcome variables will be measured for 24 participants in a trial where they receive 400 mg nitrate in the form of beetroot extract, 6 mg/kg caffeine powder, and undergo a 3 min cold pressor test. Receives: Dietary Supplement: TruBeet inorganic beetroot juice; Dietary Supplement: Caffeine; Other: Cold pressor test |
| Nitrate, placebo caffeine, and CPT | Placebo comparator | All outcome variables will be measured for 24 participants in a trial where they receive 400 mg nitrate in the form of beetroot extract, 6 mg/kg cornflour (caffeine placebo), and undergo a 3 min cold pressor test. Receives: Dietary Supplement: TruBeet inorganic beetroot juice; Other: Cold pressor test |
| Placebo nitrate, caffeine, and CPT | Placebo comparator | All outcome variables will be measured for 24 participants in a trial where they receive nitrate-depleted beetroot extract (placebo), 6 mg/kg caffeine powder, and undergo a 3 min cold pressor test. Receives: Dietary Supplement: Caffeine; Other: Cold pressor test |
| Placebo nitrate, placebo caffeine, and CPT | Placebo comparator | All outcome variables will be measured for 24 participants in a trial where they receive nitrate-depleted beetroot extract (placebo), 6 mg/kg cornflour (caffeine placebo), and undergo a 3 min cold pressor test. Receives: Other: Cold pressor test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial blood pressure
Brachial blood pressure was collected using an automatic sphygmomanometer.
Measured: Mean of 5 readings taken pre-supplementation (0 hours) and post-supplementation (2.5 hours). 1 reading was taken pre- cold pressor test (3.5 hours). All measures were recorded on every experimental trial (4 trials with at least 48 h washout between).
Flow mediated dilation
Baseline diameter, peak diameter, change in diameter, and shear stimulus following flow mediated dilation procedure of the brachial artery with post-occlusion reactive hyperaemia.
Measured: Measured pre-supplementation (at 0 hours) and post-supplementation (at 2.5 hours) for every experimental trial (4 trials with at least 48 h washout between).
Central blood pressure and pulse wave variables
Mean of 2-3 readings for aortic systolic BP, aortic diastolic BP, HR, Augmentation index, augmentation index corrected to HR of 75 bpm, pulse pressure, and augmentation pressure.
Measured: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and during the cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
Secondary outcomes (6)
Forearm blood flow
Forearm blood flow pre- and post-PORH (post occlusion reactive hyperaemia) via strain gauge plethysmography.
Measured: Measured pre-supplementation (at 0 hours) and post-supplementation (at 2.5 hours) for every experimental trial (4 trials with at least 48 h washout between).
Salivary nitrate and nitrite
Salivary concentration of nitrate and nitrite
Measured: Measured pre-supplementation (at 0 hours) and post-supplementation (at 2.5 hours) for every experimental trial (4 trials with at least 48 h washout between).
Heart rate variability
Time and frequency domains for heart rate variability collected for 3-5min.
Measured: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and during the cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
NIBP continuous blood pressure
SBP, DBP, MAP, HR collected continuously for 3-5 min.
Measured: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and during the cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
Whole blood RSNO
S--nitrosothiols concentration from treated whole blood (NEM, EDTA, potassium ferricyanide).
Measured: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and immediately post- cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
Plasma nitrate, nitrite, cGMP
Plasma concentrations of nitrate, nitrite, and cGMP.
Measured: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and immediately post- cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start5 Dec 2023
- Primary completion1 Nov 2024
- Study completion1 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NitrateStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 24 participants will complete 4 experimental conditions in a randomized order.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loughborough University
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen Extracts Pvt Ltd
- Responsible party
- Principal investigator, Stephen Bailey, Loughborough University
- Investigators
- Stephen Bailey, Principal investigator, Loughborough University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06602921
- Sponsor's protocol ID
- LoughboroughUAM
- Status last verified
- Aug 2024
- First submitted
- 12 Sep 2024
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Dietary Nitrate Supplementation Attenuate the Cardiovascular Strain Elicited by Caffeine and Cold Exposure in Healthy Individuals?
- ClinicalTrials.gov ID
- NCT06602921
- Acronym / sponsor ID
- LoughboroughUAM
- Conditions
- Nitrate, Caffeine, Cold Exposure
- Keywords
- Cardiovascular Function, Flow mediated dilation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Loughborough UniversityUniversity, hospital or other
- Collaborators
- Biogen Extracts Pvt Ltd
- Study start
- 5 Dec 2023 (actual)
- Primary completion
- 1 Nov 2024 (actual)
- Study completion
- 1 Apr 2025 (actual)
- First posted
- 19 Sep 2024 (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.
Dietary inorganic nitrate supplementation may have positive implications on cardiovascular function. The aim of this project is to determine if nitrate supplementation can attenuate the effects that caffeine and cold exposure have on the cardiovascular system.
Detailed description
Acute caffeine consumption and cold exposure elicit negative effects on the cardiovascular system. Humans are regularly exposed to such conditions of increased cardiovascular strain, which may lead to elevated chronic cardiovascular risk. On the other hand, dietary inorganic nitrate supplementation is well established to improve cardiovascular function in healthy individuals. Thus, acute nitrate supplementation may compensate for the negative effects that caffeine and the cold place on the cardiovascular system. These effects will be measured using peripheral blood pressure, pulse wave analysis, heart rate variability, forearm blood flow, flow mediated dilation, and blood and saliva markers.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- 24 participants will complete 4 experimental conditions in a randomized order.
| Arm | Type | Receives |
|---|---|---|
| Nitrate, caffeine, and cold pressor test (CPT) | Experimental | Dietary Supplement: TruBeet inorganic beetroot juice, Dietary Supplement: Caffeine, Other: Cold pressor testAll outcome variables will be measured for 24 participants in a trial where they receive 400 mg nitrate in the form of beetroot extract, 6 mg/kg caffeine powder, and undergo a 3 min cold pressor test. |
| Nitrate, placebo caffeine, and CPT | Placebo comparator | Dietary Supplement: TruBeet inorganic beetroot juice, Other: Cold pressor testAll outcome variables will be measured for 24 participants in a trial where they receive 400 mg nitrate in the form of beetroot extract, 6 mg/kg cornflour (caffeine placebo), and undergo a 3 min cold pressor test. |
| Placebo nitrate, caffeine, and CPT | Placebo comparator | Dietary Supplement: Caffeine, Other: Cold pressor testAll outcome variables will be measured for 24 participants in a trial where they receive nitrate-depleted beetroot extract (placebo), 6 mg/kg caffeine powder, and undergo a 3 min cold pressor test. |
| Placebo nitrate, placebo caffeine, and CPT | Placebo comparator | Other: Cold pressor testAll outcome variables will be measured for 24 participants in a trial where they receive nitrate-depleted beetroot extract (placebo), 6 mg/kg cornflour (caffeine placebo), and undergo a 3 min cold pressor test. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Blood pressure < 130 mmHg systolic and < 85 mmHg diastolic. BMI between 18.5 and 29.9 kg/m2. Females must be naturally menstruating (regular length cycle and menses) or using a form of combined hormonal contraception (for at least 6 months).
Key exclusion criteria (1 listed)
- Existing cardiovascular or metabolic conditions. Experience any adverse reactions to experimental procedures or supplements. Allergies to supplements or breakfast items. Involved in any other studies. Blood pressure > 130 mmHg systolic and > 85 mmHg diastolic.
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 |
|---|---|---|
| TruBeet inorganic beetroot juice400 mg nitrate-rich beetroot powder, mixed with 300 mL water. | Dietary supplement | Nitrate, caffeine, and cold pressor test (CPT), Nitrate, placebo caffeine, and CPT |
| Caffeine6 mg/kg caffeine powder in capsule form. | Dietary supplement | Nitrate, caffeine, and cold pressor test (CPT), Placebo nitrate, caffeine, and CPT |
| Cold pressor test3 min cold pressor test using the left foot in cold water (0-2 degree). | Other | Nitrate, caffeine, and cold pressor test (CPT), Nitrate, placebo caffeine, and CPT, Placebo nitrate, caffeine, and CPT, Placebo nitrate, placebo caffeine, and CPT |
Primary outcome
Brachial blood pressure
Time frame: Mean of 5 readings taken pre-supplementation (0 hours) and post-supplementation (2.5 hours). 1 reading was taken pre- cold pressor test (3.5 hours). All measures were recorded on every experimental trial (4 trials with at least 48 h washout between).
Brachial blood pressure was collected using an automatic sphygmomanometer.
Flow mediated dilation
Time frame: Measured pre-supplementation (at 0 hours) and post-supplementation (at 2.5 hours) for every experimental trial (4 trials with at least 48 h washout between).
Baseline diameter, peak diameter, change in diameter, and shear stimulus following flow mediated dilation procedure of the brachial artery with post-occlusion reactive hyperaemia.
Central blood pressure and pulse wave variables
Time frame: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and during the cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
Mean of 2-3 readings for aortic systolic BP, aortic diastolic BP, HR, Augmentation index, augmentation index corrected to HR of 75 bpm, pulse pressure, and augmentation pressure.
6 secondary outcomes
Forearm blood flow
Time frame: Measured pre-supplementation (at 0 hours) and post-supplementation (at 2.5 hours) for every experimental trial (4 trials with at least 48 h washout between).
Salivary nitrate and nitrite
Time frame: Measured pre-supplementation (at 0 hours) and post-supplementation (at 2.5 hours) for every experimental trial (4 trials with at least 48 h washout between).
Heart rate variability
Time frame: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and during the cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
NIBP continuous blood pressure
Time frame: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and during the cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
Whole blood RSNO
Time frame: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and immediately post- cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between).
Plasma nitrate, nitrite, cGMP
Time frame: Collected pre-supplementation (0 hours), post-supplementation (2.5 hours), and immediately post- cold pressor test (3.5 h) for 4 experimental trials (4 trials with at least 48 hours washout in between)
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 12 Sep 2025.
- Individual participant dataSharing planned: No
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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.
Stephen Bailey principal investigator
Loughborough University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TruBeet inorganic beetroot juice, Caffeine and Cold pressor test in people with Nitrate and Caffeine, run by Loughborough University 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 1 inclusion and 1 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 12 Sep 2025. 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.
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?
Brachial blood pressure (time frame: Mean of 5 readings taken pre-supplementation (0 hours) and post-supplementation (2.5 hours). 1 reading was taken pre- cold pressor test (3.5 hours). All measures were recorded on every experimental trial (4 trials with at least 48 h washout between).). 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?
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 12 Sep 2025.