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Completed

NCT Number: NCT05722860

L-Citrulline and Endothelial Function

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.

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Key information

Conditions

Aging

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Andriy Yabluchanskiy

Oklahoma City, Oklahoma, 73117, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

L-Citrulline, capsule

Drug

5g/daily dose for the duration of 1 week intervention

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. Change in microvascular endothelial function

    Time frame: 1 week

    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.

  2. Change in macrovascular endothelial function

    Time frame: 1 week

    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.

  3. Change in Glycocalyx - perfused boundary region

    Time frame: 1 week

    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.

  4. Change in capillary density

    Time frame: 1 week

    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.

  5. Change in red blood cell velocity

    Time frame: 1 week

    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.

  6. Change in grip strength

    Time frame: 1 week

    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

  7. Change in Attention

    Time frame: 1 week

    CANTAB research attention test.Reported as a %change from baseline, before and after treatment.

  8. Change in Working Memory

    Time frame: 1 week

    CANTAB research working memory test.Reported as a %change from baseline, before and after treatment.

  9. Change in Executive Function

    Time frame: 1 week

    CANTAB research executive function test.Reported as a %change from baseline, before and after treatment.

  10. Change in Processing Speed

    Time frame: 1 week

    CANTAB research processing speed test.Reported as a %change from baseline, before and after treatment.

  11. Blood collection

    Time frame: 1 week

    Blood samples will be collected to measure L-Citrullin related metabolites.

Sponsors and collaborators

Lead sponsor

University of Oklahoma

Other

Registry information

Official study title

Effect of Oral L-Citrulline on the Peripheral and Central Endothelial Function in Young and Older Adults

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Feb 10, 2023
Registry last updated
Mar 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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