AgingPhase 1NCT05722860
L-Citrulline and Endothelial Function
A Phase 1 study testing L-Citrulline, capsule in people with Aging, run by University of Oklahoma at 1 site in United States.
Trial summary
The effect of L-Citrulline is well studied in relation to muscle strength, exhaustion, exercise performance, and endothelial function in health and disease. This study will extend current body of knowledge and will investigate the effect of L-Citrulline on brain vascular function. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- L-Citrulline, capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2024to 28 Dec 2024
- Phase
- Phase 1
- 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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 21-45 and ≥55-90 years of age
- Adequate hearing and visual acuity to participate in the examinations
- Ability to read and write in English
- Competence to provide informed consent
Who cannot join
- Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer
- Cerebrovascular accident other than TIA within 60 days prior to Visit 0
- Major psychiatric disease, including major depression not currently controlled on medications, alcohol or drug abuse
- Treatment with other Citrulline enhancers (L-Arginine, L-Citrulline Malate) within 4 weeks prior to Visit 0
- Any other medical condition which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Oral L-Citrulline on the Peripheral and Central Endothelial Function in Young and Older Adults
The effect of L-Citrulline is well studied in relation to muscle strength, exhaustion, exercise performance, and endothelial function in health and disease. This study will extend current body of knowledge and will investigate the effect of L-Citrulline on brain vascular function.
Read the detailed description
Endothelial function is associated with nitric oxide (NO) availability for vasodilation, blood pressure and blood flow regulation, and vascular health. A large body of evidence demonstrates that aging is associated with a decrease in bioavailability of NO, with more pronounced decrease in sedentary individuals. NO can be produced via the NO synthase (NOS) enzymes, which catalyze the conversion of L-Arginine - a semi-essential amino acid found in fish, nuts and legumes amongst others - to L-Citrulline and produce NO as an endproduct. While the effect of L-Citrulline is extensively studied in relation to muscle strength, exhaustion, exercise performance, as well as on endothelial function in healthy and diseased individuals (including obese and those with heart failure), the effect of L-Citrulline on brain vascular function is not well studied.
- Conditions
- Aging
- Being tested
- L-Citrulline, capsule
- Keywords
- L-Citrulline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-Citrulline, capsuleDrug
5g/daily dose for the duration of 1 week intervention
| Study group | Role | What they receive |
|---|---|---|
| L-Citrulline | Experimental | L-Citrulline 50 g/day per os for 1 week Receives: Drug: L-Citrulline, capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in neurovascular coupling using functional near infrared spectroscopy (fNIRS)
Functional near infrared spectroscopy (fNIRS) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment. Units of measure - beta. Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Change in neurovascular coupling using the dynamic retinal vessel analysis
Flicker light-induced dilation of the retinal vessels (percentage increase over baseline diameter) will be measured in the right or left eye of each study participant using the Dynamic Vessel Analyzer (DVA, IMEDOS Systems, Jena, Germany). Units of measure mm, reported as a %change from baseline, before and after treatment.
Measured: 1 week
Change in neuronal activity
EEG signal will be collected to generate spectral data. These data will be used for comparison of EEG activity between before and after treatment. Units of measure - power spectral density. Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Secondary outcomes (11)
Change in microvascular endothelial function
Changes in microvascular endothelial function will be assessed using laser speckle contrast imaging (LSCI) in the hand using the flow mediated dilation approach. The change in skin perfusion is calculated and reported as a %change from baseline, between before and after treatment. Units of measure - perfusion index (arbitrary units). Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Change in macrovascular endothelial function
Changes in macrovascular endothelial function will be assessed using sonography during flow mediated dilation approach. The change in brachial artery diameter (mm) is calculated and reported as a %change from baseline, between before and after treatment.
Measured: 1 week
Change in Glycocalyx - perfused boundary region
Video recordings of the sublingual vasculature will be performed using the high definition video camera GlycoCheck (Microvascular health solutions). Data collected will include perfused boundary region (um), and will be used for comparison before and after treatment.
Measured: 1 week
Change in capillary density
Video recordings of the sublingual vasculature will be performed using the high definition video camera GlycoCheck (Microvascular health solutions). Data collected will include capillary density (mm/mm^2), and will be used for comparison before and after treatment.
Measured: 1 week
Change in red blood cell velocity
Video recordings of the sublingual vasculature will be performed using the high definition video camera GlycoCheck (Microvascular health solutions). Data collected will include red blood cell velocity (um/sec), and will be used for comparison before and after treatment.
Measured: 1 week
Change in grip strength
The change in hand grip strength will be measured before and after intervention. Data collected will include measurements of power in kg for left and right hand respectively
Measured: 1 week
Change in Attention
CANTAB research attention test.Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Change in Working Memory
CANTAB research working memory test.Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Change in Executive Function
CANTAB research executive function test.Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Change in Processing Speed
CANTAB research processing speed test.Reported as a %change from baseline, before and after treatment.
Measured: 1 week
Blood collection
Blood samples will be collected to measure L-Citrullin related metabolites.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start3 Jan 2024
- Primary completion28 Nov 2024
- Study completion28 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies 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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label single arm study
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andriy Yabluchanskiy, MD, PhD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05722860
- Sponsor's protocol ID
- 15485
- Status last verified
- Mar 2026
- First submitted
- 1 Feb 2023
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: PhysioNet
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral L-Citrulline on the Peripheral and Central Endothelial Function in Young and Older Adults
- ClinicalTrials.gov ID
- NCT05722860
- Acronym / sponsor ID
- 15485
- Conditions
- Aging
- Keywords
- L-Citrulline
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 3 Jan 2024 (actual)
- Primary completion
- 28 Nov 2024 (actual)
- Study completion
- 28 Dec 2024 (actual)
- First posted
- 10 Feb 2023 (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.
The effect of L-Citrulline is well studied in relation to muscle strength, exhaustion, exercise performance, and endothelial function in health and disease. This study will extend current body of knowledge and will investigate the effect of L-Citrulline on brain vascular function.
Detailed description
Endothelial function is associated with nitric oxide (NO) availability for vasodilation, blood pressure and blood flow regulation, and vascular health. A large body of evidence demonstrates that aging is associated with a decrease in bioavailability of NO, with more pronounced decrease in sedentary individuals. NO can be produced via the NO synthase (NOS) enzymes, which catalyze the conversion of L-Arginine - a semi-essential amino acid found in fish, nuts and legumes amongst others - to L-Citrulline and produce NO as an endproduct. While the effect of L-Citrulline is extensively studied in relation to muscle strength, exhaustion, exercise performance, as well as on endothelial function in healthy and diseased individuals (including obese and those with heart failure), the effect of L-Citrulline on brain vascular function is not well studied.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label single arm study
| Arm | Type | Receives |
|---|---|---|
| L-Citrulline | Experimental | Drug: L-Citrulline, capsuleL-Citrulline 50 g/day per os for 1 week |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 21-45 and ≥55-90 years of age
- Adequate hearing and visual acuity to participate in the examinations
- Ability to read and write in English
- Competence to provide informed consent
Key exclusion criteria (5 listed)
- Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer
- Cerebrovascular accident other than TIA within 60 days prior to Visit 0
- Major psychiatric disease, including major depression not currently controlled on medications, alcohol or drug abuse
- Treatment with other Citrulline enhancers (L-Arginine, L-Citrulline Malate) within 4 weeks prior to Visit 0
- Any other medical condition which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol
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 |
|---|---|---|
| L-Citrulline, capsule5g/daily dose for the duration of 1 week intervention | Drug | L-Citrulline |
Primary outcome
Change in neurovascular coupling using functional near infrared spectroscopy (fNIRS)
Time frame: 1 week
Functional near infrared spectroscopy (fNIRS) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment. Units of measure - beta. Reported as a %change from baseline, before and after treatment.
Change in neurovascular coupling using the dynamic retinal vessel analysis
Time frame: 1 week
Flicker light-induced dilation of the retinal vessels (percentage increase over baseline diameter) will be measured in the right or left eye of each study participant using the Dynamic Vessel Analyzer (DVA, IMEDOS Systems, Jena, Germany). Units of measure mm, reported as a %change from baseline, before and after treatment.
Change in neuronal activity
Time frame: 1 week
EEG signal will be collected to generate spectral data. These data will be used for comparison of EEG activity between before and after treatment. Units of measure - power spectral density. Reported as a %change from baseline, before and after treatment.
11 secondary outcomes
Change in microvascular endothelial function
Time frame: 1 week
Change in macrovascular endothelial function
Time frame: 1 week
Change in Glycocalyx - perfused boundary region
Time frame: 1 week
Change in capillary density
Time frame: 1 week
Change in red blood cell velocity
Time frame: 1 week
Change in grip strength
Time frame: 1 week
Change in Attention
Time frame: 1 week
Change in Working Memory
Time frame: 1 week
Change in Executive Function
Time frame: 1 week
Change in Processing Speed
Time frame: 1 week
Blood collection
Time frame: 1 week
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 Mar 2026.
- Individual participant dataSharing planned: No. PhysioNet
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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.
Andriy Yabluchanskiy, MD, PhD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing L-Citrulline, capsule in people with Aging, run by University of Oklahoma at 1 site in United States.
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 5 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 Mar 2026. 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 States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Change in neurovascular coupling using functional near infrared spectroscopy (fNIRS) (time frame: 1 week). 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 Mar 2026.