Investigating the Effect of Caffeine and Alcohol on Pupil Dynamics

Официальное название

Investigating the Effect of Caffeine and Alcohol on Pupil Dynamics (PAC)

Обзор

The goal of this study is to understand how caffeine and alcohol affect the ocular and physiological systems, especially how the pupil (the aperture in the colored part of the eye) responds to light. It will also test whether these changes can be used to detect recent caffeine or alcohol intake using a portable eye device. The main questions it aims to answer are: 1. How does caffeine change pupil responses, eye movements, and other ocular and physiological measurements? 2. How does alcohol change these same ocular and physiological responses? 3. Are the effects of caffeine and alcohol different from each other? 4. Can these changes be used to accurately identify whether someone has consumed caffeine or alcohol? Researchers will compare caffeine, alcohol, and a placebo (a look-alike drink with no active substance) to see how each affects the ocular and physiological outcomes. Participants will: 1. Attend three separate sessions where they will consume caffeine, alcohol, or a placebo (in random order) 2. Undergo pupillary response evaluation using a handheld device that measures responses to different colored light stimuli 3. Have their eye movements analyzed 4. Have retinal and choroidal thickness, blood perfusion, and ocular oxygen levels measured 5. Have basic body measurements recorded (such as pulse rate and blood pressure) 6. Complete tests at multiple time points over 2 hours after consumption The results of this study may help develop a quick and non-invasive way to detect recent caffeine or alcohol use for clinical and safety purposes.

Подробное описание

Caffeine and alcohol are widely consumed psychoactive substances that affect the central and autonomic nervous systems. These effects can influence ocular function, including pupil responses to light, eye movements, and retinal physiology. However, objective and non-invasive methods to detect and differentiate these effects remain limited.

The pupillary light reflex is a sensitive indicator of autonomic nervous system activity. Chromatic pupillometry, which uses different colored light stimuli, allows assessment of specific retinal pathways and provides detailed information about pupil function. This study aims to determine whether changes in pupillary responses and other ocular measurements can be used to detect recent caffeine or alcohol consumption.

Study Design and Procedures A total of 100 healthy adults aged 30-50 years will participate in this study.

Each participant will attend three study visits, corresponding to the following conditions:

1. Caffeine condition (\~3 mg/kg) 2. Alcohol condition (target blood alcohol concentration \~0.05%) 3. Placebo condition The order of conditions will be randomized. This is a double-masked, within-subject crossover study, where each participant undergoes all three conditions.

Study Visit Procedures

At each visit, participants will receive one tablet and one beverage according to the assigned condition:

1. Placebo condition: placebo tablet with a non-alcoholic beverage 2. Alcohol condition: placebo tablet with an alcohol-containing beverage 3. Caffeine condition: caffeine tablet with a non-alcoholic beverage Procedures will be standardized to maintain masking, and study personnel performing assessments will remain unaware of the assigned condition.

Assessments All measurements will be performed at baseline (before consumption) and at 30, 60, 90, and 120 minutes after consumption, unless otherwise specified.

1. Pupillary Assessment: Pupillary responses will be measured using a handheld chromatic pupillometry device in a controlled dark environment. Different colored light stimuli will be used to assess pupil function. 2. Eye Movement Analysis: Eye movements will be recorded to evaluate oculomotor function, including tracking, fixation, and gaze behavior at baseline, 60 minutes, and 120 minutes. 3. Retinal and Choroidal Imaging: Retinal and choroidal thickness and blood perfusion will be measured using optical coherence tomography (OCT) and OCT angiography at baseline, 60 minutes, and 120 minutes. 4. Breath Alcohol Measurement: Breath alcohol concentration will be measured using a breathalyzer at all time points to monitor alcohol levels. 5. Physiological Measurements: Basic physiological parameters will be recorded, including: Pulse rate, Blood pressure, Blood Oxygen saturation

Data Analysis Data from pupillary responses, eye movements, retinal imaging, and physiological measurements will be combined to identify patterns associated with caffeine and alcohol intake.

Expected Outcomes This study aims to identify measurable changes in pupil responses and other ocular parameters following caffeine and alcohol consumption. It will also evaluate whether a portable, non-invasive system can be used to detect alcohol and caffeine consumption.

The findings may support the development of rapid and objective screening tools for clinical, occupational, and public safety applications.

Вмешательства

• Другое Placebo Comparator: Placebo
  Participants receive a matched placebo tablet together with a non-alcoholic beverage identical in appearance and volume to the active conditions. A cornstarch-based formulation may be used for the placebo tablet. Beverage presentation is standardized to maintain blinding across study conditions. No active caffeine or alcohol is administered.
• Другое Caffeine administration
  Participants receive a single oral dose of caffeine (\~3 mg/kg body weight) administered in tablet form. The caffeine is given with a non-alcoholic beverage matched to study conditions. All procedures are performed under randomized, double-masked crossover design conditions.
• Другое Alcohol (Ethanol)
  Participants consume a standardized alcoholic beverage designed to achieve a target blood alcohol concentration of approximately 0.05%. A placebo tablet is administered alongside the beverage to maintain masking. All procedures are performed under randomized, double-masked crossover design conditions.

Первичные конечные точки

• Baseline Pupil Size [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Phasic Pupil Constriction to Blue Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Maximum Pupil Constriction to Blue Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Pupil Constriction Latency to Blue Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Phasic Pupil Constriction to Red Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Maximum Pupil Constriction to Red Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Pupil Constriction Latency to Red Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Phasic Pupil Constriction to Continuous White Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Maximum Pupil Constriction to Continuous White Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Pupil Constriction Latency to Continuous White Light [Срок оценки: Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]

Вторичные конечные точки (12)

• Retinal Thickness [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Choroidal Thickness [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Superficial Capillary Plexus Vessel Density [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Deep Capillary Plexus Vessel Density [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Choriocapillaris Vessel Density [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Foveal Avascular Zone Area [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Choroidal Vascularity Index [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Prosaccade Latency [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Prosaccade Peak Velocity [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Prosaccade Amplitude [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Smooth Pursuit Gain [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]
• Catch-Up Saccade Frequency During Smooth Pursuit [Срок оценки: Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)]

Критерии участия

Participants must meet the inclusion criteria, as shown below, to participate in this study

Критерии включения

• Age: 30 to 50 years of age
• Visual Acuity: Best Corrected Visual Acuity (BCVA) of 0.20 LogMAR or better in both eyes
• Ability to provide informed consent: Participants must be able to understand and sign the informed consent form
• Ability to consume both caffeine and alcohol: Participants must be willing and able to consume caffeine and alcohol as part of the study

Participants meeting any of the exclusion criteria, as shown in the table below, will be excluded from participation.

Критерии исключения

• Diagnosed ocular conditions: Participants with ocular or ocular movement diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, amblyopia, severe ptosis, or conditions relating to pupils: anisocoria, irregular pupil, Adie tonic, Horner's syndrome, Argyll Robertson pupil, etc. These exclude cataracts, refractive errors, and any ocular condition not affecting vision or ocular movement or obstructing the pupil.
• Diagnosed and unresolved neurological conditions:Stroke, unresolved traumatic brain injury, space-occupying lesions in the brain, neuropathies, demyelinating conditions, nerve palsies, etc.
• Diagnosed systemic conditions that may restrict the participant from drinking caffeine or alcohol: Hypertension, cardiovascular disease, liver disease, kidney disease, etc.
• Medications: Participants taking any medications that may interact with caffeine or alcohol, affect alertness, or cause drowsiness
• Previous complex intraocular eye surgery: Participants who have undergone any eye surgery other than uncomplicated refractive surgery.
• Pregnancy or breastfeeding: Pregnant or breastfeeding women will be excluded from the study, as caffeine and alcohol can affect the fetus or baby
• History of substance abuse: Participants with a history of substance abuse
• Allergies or sensitivities: Participants with allergies or sensitivities to caffeine or alcohol
• Shift work or having travelled across 2 time zones over the past 2 weeks: This is essential to avoid any impact of sleep deprivation on our outcome measures
• Non-consumers or light-consumers of caffeine and alcohol Participants who are light consumers of caffeine or alcohol will be excluded due to higher sensitivity to side effects.

Caffeine: If less than 100 mg of caffeine per week from all sources (including coffee, soft drinks, energy drinks, chocolate, and medications) based on the CCQ\* Alcohol: If AUDIT-C\*\* score less than 1

11- Extremely frequent consumers Participants who are extremely frequent consumers of caffeine or alcohol will be excluded due to potential withdrawal symptoms during the required 18-hour abstinence and possible reduced sensitivity to administered doses.

Caffeine: If more than 400mg of caffeine (e.g., 5 espressos) per day from all sources (including coffee, soft drinks, energy drinks, chocolate, and medications) based on the CCQ\* Alcohol: If AUDIT-C\*\* scores more than 4 for men and more than 3 for women

Note: Participants will complete a history update questionnaire at each laboratory visit to report any changes relevant to the exclusion criteria. If a participant no longer meets the eligibility criteria at any visit after the baseline assessment, the visit will either be rescheduled, if appropriate, or the participant will be withdrawn from the study. Reimbursement will be provided on a prorated basis.

\*CCQ: Caffeine Consumption Questionnaire

\*\*AUDIT-C: Alcohol Use Disorders Identification Test-C

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Диагностика

Центры проведения

Сингапур · 1 центр

• National University of Singapore, E7 Building, Level 7, 15 Kent Ridge Cres — Singapore

Публикации

• Silva JBS, Cristino ED, Almeida NL, Medeiros PCB, Santos NAD. Effects of acute alcohol ingestion on eye movements and cognition: A double-blind, placebo-controlled study. PLoS One. 2017 Oct 12;12(10):e0186061. doi: 10.1371/journal.pone.0186061. eCollection 2017. PMID 29023550
• Bardak H, Gunay M, Mumcu U, Bardak Y. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects. Biomed Res Int. 2016;2016:9578308. doi: 10.1155/2016/9578308. Epub 2016 Jun 29. PMID 27437402
• Wilhelm B, Stuiber G, Ludtke H, Wilhelm H. The effect of caffeine on spontaneous pupillary oscillations. Ophthalmic Physiol Opt. 2014 Jan;34(1):73-81. doi: 10.1111/opo.12094. PMID 24325436
• Redondo B, Vera J, Carreno-Rodriguez C, Molina-Romero R, Jimenez R. Acute Effects of Caffeine on Dynamic Accommodative Response and Pupil Size: A Placebo-controlled, Double-blind, Balanced Crossover Study. Curr Eye Res. 2020 Sep;45(9):1074-1081. doi: 10.1080/02713683.2020.1725060. Epub 2020 Feb 11. PMID 32011181
• Abokyi S, Owusu-Mensah J, Osei KA. Caffeine intake is associated with pupil dilation and enhanced accommodation. Eye (Lond). 2017 Apr;31(4):615-619. doi: 10.1038/eye.2016.288. Epub 2016 Dec 16. PMID 27983733
• Rukmini AV, Milea D, Gooley JJ. Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases. Front Neurol. 2019 Feb 12;10:76. doi: 10.3389/fneur.2019.00076. eCollection 2019. PMID 30809186

Идентификаторы

NCT: NCT07625358 · NUS-IRB-2025-1150

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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