HypertensionNCT02214290
Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males
A study testing Caffeine and L-citrulline in people with Hypertension and Healthy, run by Florida State University.
Trial summary
Caffeine is an exceedingly popular and consumed pharmacological agent. Although caffeine is primarily consumed from coffee and tea beverages, it is also available in other forms such as sodas, energy drinks, tablets and capsules. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Healthy
- What is being tested?
- Caffeine and L-citrulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- No sites listed yet
- Study dates
- Sep 2012to Mar 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Young healthy males
- Non smoker
- Non endurance trained athlete
- No previous history of cardiovascular disease
Who cannot join
- Female
- Blood pressure greater than 160/100
- Smoker
About this study
Caffeine is an exceedingly popular and consumed pharmacological agent. Although caffeine is primarily consumed from coffee and tea beverages, it is also available in other forms such as sodas, energy drinks, tablets and capsules. Nevertheless, caffeine acutely increases brachial and aortic systolic blood pressure (BP) and arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular disease (CVD) and assessed through pulse wave velocity (PWV). Interestingly, previous studies have proposed that caffeine may increase aortic BP through increases in aortic PWV and augmentation index (AIx), a measurement of wave reflection. Yet, these effects were seen in middle-aged adults with treated hypertension and a wide age range. Therefore, it is imperative to consider that caffeine may cause different effects in young normotensive individuals than in older adults independently of BP levels. Importantly, oral supplementation of the amino-acid, L-citrulline has been shown to enhance the bioavailability of L-arginine levels and nitric oxide (NO) production and, therefore, improve arterial function. L-citrulline supplementation for 7 days given at 6 g/day has shown to increase NO levels while improving PWV. Previous studies by our group also demonstrated that L-citrulline supplementation reduces the BP response to cold exposure; a condition with an increased vasoconstriction. Therefore, the acute effects of caffeine on central and peripheral PWV and BP in healthy young men are yet to be fully evaluated. We hypothesized that acute caffeine intake would increase peripheral and aortic BP and PWV and that L-citrulline supplementation would attenuate the effects induced by acute caffeine ingestion.
Read the detailed description
The specific aims of this study are:
AIM 1: To examine the effects of the acute ingestion of 200mg caffeine (tablets) on arterial function in young adults. The working hypothesis is that acute caffeine intake would increase brachial, ankle and aortic BP, PWV (aortic and leg), and wave reflection. In order to test this hypothesis, the investigators will perform non-invasive measurements of arterial stiffness (aortic and leg PWV) and pulse wave analysis (aortic BP and AIx) using applanation tonometry of the radial artery 30, 45, and 60 minutes following caffeine ingestion.
AIM 2: To determine the effectiveness of L-citrulline supplementation to attenuate the acute cardiovascular effects of caffeine ingestion. The working hypothesis is that 7 days of L-citrulline supplementation will attenuate the unfavorable arterial responses (increases in BP, PWV, and wave reflection) to acute caffeine ingestion. In order to test this hypothesis, the investigators will perform the same procedures previously specified in AIM 1.
Description of the study:
Sixteen healthy young men 18-40 years of age will be enrolled in this study. Participants with CVD history, resting BP (> 160/100 mmHg), recent history of smoking, or considered competitive athlete will be excluded from the study. All subjects will refrain from food and caffeine for > 8 hours and from exercise for > 24 hours before testing.
Study design:
Following an initial screening, arterial function measurements will be collected. Measurements will be assessed at baseline following 10 minutes of rest in the supine position and then again at 30, 45, and 60 minutes after 200 mg caffeine or placebo ingestion. Participants will receive caffeine or placebo supplementation on two separate visits with a minimum of 48 hours in between sessions. Following the acute phase of the study, subjects will be randomized to consume L-citrulline or placebo for 7 days given at 6 grams/day. Following the same protocol as the acute phase with 200 mg caffeine, measurements will be collected before and after the 7 day supplementation period.
- Conditions
- Hypertension, Healthy
- Being tested
- Caffeine, Placebo, L-citrulline
- Keywords
- Cardiovascular, Caffeine, L-citrulline, Arterial Function, Hemodynamics, Blood Pressure, Pulse Wave Velocity, Pulse Wave Analysis
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDrug
Also called Caffeine tablet (CVS Pharmacy)
A 200 mg caffeine tablet was given to subject to examine the drugs effect on arterial function.
PlaceboDrug
Also called Placebo from NOW FOODS, USA
A 750 mg placebo capsule (maltodextrin) was given to subjects to examine the effect of the drug on arterial function.
L-citrullineDietary supplement
Also called L-citrulline (750 mg/capsule)
L-citrulline was used to examine the effect of the supplement on arterial function.
| Study group | Role | What they receive |
|---|---|---|
| Caffeine | Active comparator | 200 mg caffeine tablet produced by CVS Pharmacy, USA Receives: Drug: Caffeine |
| Placebo | Placebo comparator | Placebo pill produced by NOW FOODS, USA Receives: Drug: Placebo |
| L-citrulline | Experimental | L-citrulline capsule (750 mg) provided by NOW FOODS Receives: Dietary Supplement: L-citrulline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aortic Blood Pressure
Aortic blood pressure at rest and 30 minutes after acute ingestion of 200 mg of caffeine before and after 7 days of either 6g/day of Citrulline or 6 g/day of Placebo.
Measured: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)
Secondary outcomes (2)
Changes in Reflected Wave Pressure (P2)
Reflected wave pressure at rest and 30 minutes after ingestion of 200mg of caffeine after 7 days supplementation of 6g/day of either L-Citrulline or Placebo.
Measured: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)
Changes in Femoral-ankle Pulse Wave Velocity After 7 Days of Either L-Citrulline or Placebo (6g/Day)
Femoral-ankle pulse wave velocity at rest and 30 minutes after ingestion of 200mg of caffeine after 7 days supplementation of 6g/day of either L-Citrulline or Placebo.
Measured: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2014 (estimated)
- Study startSep 2012
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Florida State UniversityThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Florida State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arturo Figueroa, Florida State University
- Investigators
- Arturo Figueroa, M.D. Ph.D, Principal investigator, Florida State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02214290
- Sponsor's protocol ID
- HSC2013.10514
- Status last verified
- Oct 2020
- First submitted
- 4 Aug 2014
- Last updated
- 29 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males
- ClinicalTrials.gov ID
- NCT02214290
- Acronym / sponsor ID
- HSC2013.10514
- Conditions
- Hypertension, Healthy
- Keywords
- Cardiovascular, Caffeine, L-citrulline, Arterial Function, Hemodynamics, Blood Pressure, Pulse Wave Velocity, Pulse Wave Analysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Florida State UniversityUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 12 Aug 2014 (estimated)
- Results
- Posted 29 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Caffeine is an exceedingly popular and consumed pharmacological agent. Although caffeine is primarily consumed from coffee and tea beverages, it is also available in other forms such as sodas, energy drinks, tablets and capsules. Nevertheless, caffeine acutely increases brachial and aortic systolic blood pressure (BP) and arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular disease (CVD) and assessed through pulse wave velocity (PWV). Interestingly, previous studies have proposed that caffeine may increase aortic BP through increases in aortic PWV and augmentation index (AIx), a measurement of wave reflection. Yet, these effects were seen in middle-aged adults with treated hypertension and a wide age range. Therefore, it is imperative to consider that caffeine may cause different effects in young normotensive individuals than in older adults independently of BP levels. Importantly, oral supplementation of the amino-acid, L-citrulline has been shown to enhance the bioavailability of L-arginine levels and nitric oxide (NO) production and, therefore, improve arterial function. L-citrulline supplementation for 7 days given at 6 g/day has shown to increase NO levels while improving PWV. Previous studies by our group also demonstrated that L-citrulline supplementation reduces the BP response to cold exposure; a condition with an increased vasoconstriction. Therefore, the acute effects of caffeine on central and peripheral PWV and BP in healthy young men are yet to be fully evaluated. We hypothesized that acute caffeine intake would increase peripheral and aortic BP and PWV and that L-citrulline supplementation would attenuate the effects induced by acute caffeine ingestion.
Detailed description
The specific aims of this study are:
AIM 1: To examine the effects of the acute ingestion of 200mg caffeine (tablets) on arterial function in young adults. The working hypothesis is that acute caffeine intake would increase brachial, ankle and aortic BP, PWV (aortic and leg), and wave reflection. In order to test this hypothesis, the investigators will perform non-invasive measurements of arterial stiffness (aortic and leg PWV) and pulse wave analysis (aortic BP and AIx) using applanation tonometry of the radial artery 30, 45, and 60 minutes following caffeine ingestion.
AIM 2: To determine the effectiveness of L-citrulline supplementation to attenuate the acute cardiovascular effects of caffeine ingestion. The working hypothesis is that 7 days of L-citrulline supplementation will attenuate the unfavorable arterial responses (increases in BP, PWV, and wave reflection) to acute caffeine ingestion. In order to test this hypothesis, the investigators will perform the same procedures previously specified in AIM 1.
Description of the study:
Sixteen healthy young men 18-40 years of age will be enrolled in this study. Participants with CVD history, resting BP (> 160/100 mmHg), recent history of smoking, or considered competitive athlete will be excluded from the study. All subjects will refrain from food and caffeine for > 8 hours and from exercise for > 24 hours before testing.
Study design:
Following an initial screening, arterial function measurements will be collected. Measurements will be assessed at baseline following 10 minutes of rest in the supine position and then again at 30, 45, and 60 minutes after 200 mg caffeine or placebo ingestion. Participants will receive caffeine or placebo supplementation on two separate visits with a minimum of 48 hours in between sessions. Following the acute phase of the study, subjects will be randomized to consume L-citrulline or placebo for 7 days given at 6 grams/day. Following the same protocol as the acute phase with 200 mg caffeine, measurements will be collected before and after the 7 day supplementation period.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Caffeine | Active comparator | Drug: Caffeine200 mg caffeine tablet produced by CVS Pharmacy, USA |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo pill produced by NOW FOODS, USA |
| L-citrulline | Experimental | Dietary Supplement: L-citrullineL-citrulline capsule (750 mg) provided by NOW FOODS |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Young healthy males
- Non smoker
- Non endurance trained athlete
- No previous history of cardiovascular disease
Key exclusion criteria (3 listed)
- Female
- Blood pressure greater than 160/100
- Smoker
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 |
|---|---|---|
| CaffeineAlso: Caffeine tablet (CVS Pharmacy)A 200 mg caffeine tablet was given to subject to examine the drugs effect on arterial function. | Drug | Caffeine |
| PlaceboAlso: Placebo from NOW FOODS, USAA 750 mg placebo capsule (maltodextrin) was given to subjects to examine the effect of the drug on arterial function. | Drug | Placebo |
| L-citrullineAlso: L-citrulline (750 mg/capsule)L-citrulline was used to examine the effect of the supplement on arterial function. | Dietary supplement | L-citrulline |
Primary outcome
Aortic Blood Pressure
Time frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)
Aortic blood pressure at rest and 30 minutes after acute ingestion of 200 mg of caffeine before and after 7 days of either 6g/day of Citrulline or 6 g/day of Placebo.
2 secondary outcomes
Changes in Reflected Wave Pressure (P2)
Time frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)
Changes in Femoral-ankle Pulse Wave Velocity After 7 Days of Either L-Citrulline or Placebo (6g/Day)
Time frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Arturo Figueroa, M.D. Ph.D principal investigator
Florida State University
Questions about this trial
What is this clinical trial studying?
A study testing Caffeine and L-citrulline in people with Hypertension and Healthy, run by Florida State University.
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 4 inclusion and 3 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 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 29 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Aortic Blood Pressure (time frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points)). 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 29 Dec 2020.