Caffeine and Cerebrovascular Reactivity

NCT04730193 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 12731
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Caffeine

Keywords

caffeine; Cerebrovascular reactivity; Retinal reactivity

Outcome Measures

Primary Outcomes (5)

• Modified Caffeine Research Visual Analogue Scales

  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.

  Change from baseline measurements 1 hour after treatment

• Static retinal vessel assessment

  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.

  Change from baseline measurements 1 hour after treatment

• Dynamic retinal vessel assessment

  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.

  Change from baseline measurements 1 hour after treatment

• Cerebrovascular reactivity using transcranial Doppler

  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.

  Change from baseline measurements 1 hour after treatment

• Cerebrovascular reactivity using functional near infrared spectroscopy (fNIRS)

  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.

  Change from baseline measurements 1 hour after treatment

Study Arms (2)

Control

PLACEBO COMPARATOR

Participants randomized to placebo group will receive placebo capsule

Drug: Placebo

Caffeine

EXPERIMENTAL

Participants randomized to caffeine group will receive 100mg caffeine capsule

Drug: Caffeine

Interventions

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

Also known as: Trimethylxanthine

Caffeine

Placebo DRUG

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

Control

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

Translational GeroScience Laboratory

Oklahoma City, Oklahoma, 73117, United States

Location

MeSH Terms

Interventions

Caffeine

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andriy Yabluchanskiy, MD, PhD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigator, and outcomes assessors are blinded
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 29, 2021
• Study Start: February 1, 2021
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2022
• Last Updated: August 9, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)