Caffeine and Cerebrovascular Reactivity
Condition: Caffeine
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Caffeine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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; Placebo pill will be formulated with a non active ingredient such as rice flour powder
Other intervention name(s): Trimethylxanthine
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
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
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: caffeine; Cerebrovascular reactivity; Retinal reactivity