Caffeine
Conditions
Keywords
caffeine, Cerebrovascular reactivity, Retinal reactivity
Brief summary
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.
Detailed description
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.
Interventions
DRUGCaffeine
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
DRUGPlacebo
Placebo pill will be formulated with a non active ingredient such as rice flour powder
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants, investigator, and outcomes assessors are blinded
Intervention model description
subject will take drug A on first session and measurements will be performed at baseline and 1 hour after treatment; subject will come for second visit in 5-7 days and take drug B, measurements will be performed at baseline and 1 hour after treatment
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Caffeine Research Visual Analogue Scales | 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. |
| Static retinal vessel assessment | 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. |
| Dynamic retinal vessel assessment | 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. |
| Cerebrovascular reactivity using transcranial Doppler | 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. |
| Cerebrovascular reactivity using functional near infrared spectroscopy (fNIRS) | 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. |
Countries
United States
Outcome results
None listed