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Completed

NCT Number: NCT04730193

Caffeine and Cerebrovascular Reactivity

Caffeine is the most commonly used stimulant drug with well documented effects on cerebral vascula-ture. Caffeine is known to non-specifically bind to adenosine receptors in the brain and to reduce resting blood flow while improving attention and cognitive function, which suggests that it may allow a more efficient dynamic blood flow regulation through neurovascular coupling. This study will use standardized dose of caffeine to test its effect on NVC responses in cerebral and retinal arterioles.

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Key information

Conditions

Caffeine

Age range

21 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Translational GeroScience Laboratory

Oklahoma City, Oklahoma, 73117, United States

About this study

Normal brain function is critically dependent on moment-to-moment adjustment of cerebral blood flow to match demands of activated neurons. This process is known as neurovascular coupling (NVC) and recent in vivo studies demonstrate that impairment of NVC responses is associated with worse cognitive performance. Several methods are available to measure NVC responses in human subjects, including transcranial Doppler (TCD), functional near infrared spectroscopy (fNIRS), and dynamic retinal vessel analysis (DVA). Although all these methodologies aim to measure hemodynamic changes in the brain vasculature in response to cognitive, motor, or visual stimulation, the responses are evaluated on the different levels of cerebral vasculature including microvasculature (fNIRS), large cerebral vessels such as middle cerebral artery (TCD), or in the arterioles and venules of the retina (DVA). Currently, there are limited data available on the simultaneous assessment of NVC responses using these methodologies.

Caffeine is the most commonly used stimulant drug with well documented effects on cerebral vasculature. Caffeine is known to non-specifically bind to adenosine receptors in the brain and to reduce resting blood flow while improving attention and cognitive function, which suggests that it may allow a more efficient dynamic blood flow regulation through neurovascular coupling. This study will use standardized dose of caffeine to test its effect on NVC responses in cerebral and retinal arterioles.

This study is designed to establish the direct link between reactivity in the cerebral and retinal micro- and macrovasculature. To achieve this goal, a prospective, single-blinded, placebo controlled, cross-over study will be employed to evaluate changes in the NVC responses measured simultaneously with DVA and TCD, or DVA and fNIRS before and after administration of 100mg of incapsulated caffeine or placebo pill.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • English speaking
  • Ability to read and write in English
  • Competence to provide informed consent
  • Non-occludable angle and with no optic neuropathy
  • Subjects will be asked to refrain from caffeine consumption for at least 8 hours before participating in the study

Exclusion criteria

  • The history of photosensitive epilepsy
  • Intraocular pressure 21 Hgmm or higher
  • Eyes with a visual acuity 20/30 or lower or the inability to fixate on fixation markers
  • Previous symptoms of glaucoma attack (severe ocular pain and redness, decreased vision, colored halos in combination with headache, nausea and vomiting).
  • Known allergies to study drugs
  • Pregnancy and breast feeding
  • Significant cardiac disease (e.g. heart failure), chest pain in the last 6 months
  • Stage-2 high blood pressure not controlled by medication (>160/100 mm Hg)
  • Uncontrolled diabetes mellitus; History of stroke; Multiple sclerosis; Chronic obstructive pulmonary disease; Active cancer; Abnormal liver function
  • Diagnosis of dementia; Anxiety Disorder
  • Absent temporal acoustic windows, intracranial stenosis (for TCD-related studies)
  • History of arrhythmias
  • Prisoners

Treatment and study plan

Caffeine

Drug

Caffeine, also known as Trimethylxanthine, will be purchased through the University of Oklahoma Health Sciences Pharmacy and formulated into capsule pills containing 100mg of active ingredient

Other names: Trimethylxanthine

Placebo

Drug

Placebo pill will be formulated with a non active ingredient such as rice flour powder

Primary outcomes

  1. Modified Caffeine Research Visual Analogue Scales

    Time frame: Change from baseline measurements 1 hour after treatment

    Caffeine Research Visual Analogue Scales consists of seven visual analogue scales ("relaxed", "alert", "jittery", "tired", "tense", "headache", overall mood") are measured from 1 to 10 and have previously been used in research to evaluate the effects of caffeine. A single "mentally fatigued" visual analogue scale (scored from 1 to 10) will be included, as previous research has shown it to be sensitive to a caffeine-glucose drink.

  2. Static retinal vessel assessment

    Time frame: Change from baseline measurements 1 hour after treatment

    Static analysis of retinal vasculature will be performed to evaluate averaged retinal arteriole and venule calibers. A ratio of these two measurements will be used to calculate arteriole-venule ratio.

  3. Dynamic retinal vessel assessment

    Time frame: Change from baseline measurements 1 hour after treatment

    Flicker light-induced dilation of the retinal vessels (percentage increase over baseline diameter) will be measured in the right eye of each subject using the Dynamic Vessel Analyzer (DVA, IMEDOS Systems, Jena, Germany). The change in retinal vessel diameters is tracked and reported as a %change from baseline.

  4. Cerebrovascular reactivity using transcranial Doppler

    Time frame: Change from baseline measurements 1 hour after treatment

    Transcranial Doppler sonography will be assessed simultaneously with the dynamic retinal vessel analysis and the blood flow velocity will be measured in the posterior cerebral artery. Change in the blood flow velocities from baseline will be measured.

  5. Cerebrovascular reactivity using functional near infrared spectroscopy (fNIRS)

    Time frame: Change from baseline measurements 1 hour after treatment

    Functional near infrared spectroscopy (fNIRS) will be performed during the finger tapping task or go-no-go cognitive task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Cerebrovascular reactivity will be evaluated as a change in oxy- and deoxy-hemoglobin between "during" and "before" task.

Sponsors and collaborators

Lead sponsor

University of Oklahoma

Other

Registry information

Official study title

The Effect of Caffeine on Cerebrovascular and Retinal Microvessel Reactivity

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Jan 29, 2021
Registry last updated
Aug 9, 2022

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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