NCT07625358

Brief Summary

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. 1.How does caffeine change pupil responses, eye movements, and other ocular and physiological measurements?
  2. 2.How does alcohol change these same ocular and physiological responses?
  3. 3.Are the effects of caffeine and alcohol different from each other?
  4. 4.Can these changes be used to accurately identify whether someone has consumed caffeine or alcohol?
  5. 5.Attend three separate sessions where they will consume caffeine, alcohol, or a placebo (in random order)
  6. 6.Undergo pupillary response evaluation using a handheld device that measures responses to different colored light stimuli
  7. 7.Have their eye movements analyzed
  8. 8.Have retinal and choroidal thickness, blood perfusion, and ocular oxygen levels measured
  9. 9.Have basic body measurements recorded (such as pulse rate and blood pressure)
  10. 10.Complete tests at multiple time points over 2 hours after consumption

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for not_applicable

Timeline
17mo left

Started Jun 2026

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress3%
Jun 2026Nov 2027

First Submitted

Initial submission to the registry

May 18, 2026

Completed
14 days until next milestone

Study Start

First participant enrolled

June 1, 2026

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 4, 2026

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 5, 2027

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 5, 2027

Last Updated

June 4, 2026

Status Verified

May 1, 2026

Enrollment Period

11 months

First QC Date

May 18, 2026

Last Update Submit

May 28, 2026

Conditions

CaffeineAlcoholPupillary ResponseEye MovementsOptical Coherence TomographyPhysiological ResponsesOptical Coherence Tomography Angiography

Keywords

CaffeineAlcoholPupillary light reflexPupillometryChromatic pupillometryEye movementsOculomotor functionOptical coherence tomographyOptical coherence tomography angiographyPhysiological responsesMachine learningNon-invasive monitoring

Outcome Measures

Primary Outcomes (24)

  • Baseline Pupil Size

    Baseline pupil size will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Baseline pupil size refers to the resting pupil diameter measured prior to light stimulation. It is measured in pixels.

    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

    Phasic pupil constriction to blue light will be quantified using handheld chromatic pupillometry. Phasic pupil constriction to blue light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a blue light stimulus. It is calculated as a percentage change from baseline.

    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

    Maximum pupil constriction to blue light will be quantified using handheld chromatic pupillometry. Maximum pupil constriction to blue light refers to the greatest reduction in pupil diameter observed following the onset of a blue light stimulus. It is calculated as a percentage change from baseline.

    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

    Pupil constriction latency to blue light will be quantified using handheld chromatic pupillometry. Constriction latency is defined as the time from blue light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds or milliseconds.

    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

    Phasic pupil constriction to red light will be quantified using handheld chromatic pupillometry. Phasic pupil constriction to red light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a red light stimulus. It is calculated as a percentage change from baseline.

    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

    Maximum pupil constriction to red light will be quantified using handheld chromatic pupillometry. Maximum pupil constriction to red light refers to the greatest reduction in pupil diameter observed following the onset of a red light stimulus. It is calculated as a percentage change from baseline.

    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

    Pupil constriction latency to red light will be quantified using handheld chromatic pupillometry. Constriction latency is defined as the time from red light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds or milliseconds.

    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

    Phasic pupil constriction to continuous white light will be quantified using handheld chromatic pupillometry. Phasic pupil constriction to white light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a white light stimulus. It is calculated as a percentage change from baseline.

    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

    Maximum pupil constriction to continuous white light will be quantified using handheld chromatic pupillometry. Maximum pupil constriction to white light refers to the greatest reduction in pupil diameter observed following the onset of a white light stimulus. It is calculated as a percentage change from baseline.

    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

    Pupil constriction latency to continuous white light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Constriction latency is defined as the time from white light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds.

    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 White Light Flash

    Maximum pupil constriction to white light flash will be quantified using using handheld chromatic pupillometry. Maximum pupil constriction to white light refers to the greatest reduction in pupil diameter observed following the onset of a white light stimulus. It is calculated as a percentage change from baseline.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Post-Stimulus Pupil Recovery Slope to Blue Light

    Post-stimulus pupil recovery slope to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a blue light stimulus. It is calculated as percentage change per second.

    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 Slope to Blue Light 1.7s before Blue Light Offset

    Pupil slope to blue light 1.7s before blue light offset will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Pupil slope to blue light within the last 1.7s refers to the rate of pupil re-dilation just before the offset of a blue light stimulus. It is calculated as percentage change per second.

    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 Slope to Blue Light 1.7s after Blue Light Offset

    Pupil slope to blue light in the 1.7s after blue light offset will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Pupil slope to blue light in the 1.7s after blue light offset refers to the rate of pupil re-dilation just after the offset of a blue light stimulus. It is calculated as percentage change per second.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Post-Stimulus Pupil Recovery Slope to Red Light

    Post-stimulus pupil recovery slope to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a red light stimulus. It is calculated as percentage change per second.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Post-Stimulus Pupil Recovery Slope to White Light Flash

    Post-stimulus pupil recovery slope to white light flash will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a white light stimulus. It is calculated as percentage change per second.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Post-Stimulus Pupil Recovery Slope to Continuous White Light

    Post-stimulus pupil recovery slope to continuous white light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Post-stimulus pupil recovery slope refers to the rate of pupil re-dilation following the offset of a white light stimulus. It is calculated as percentage change per second.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR at 6 s - Blue Light

    Post-illumination pupillary responses (PIPR) to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after blue light offset. It is calculated as a percentage of baseline pupil size.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR at 12 s - Blue Light

    Post-illumination pupillary responses (PIPR) to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 12 s is measured as pupil size at 12 seconds after blue light offset. It is calculated as a percentage of baseline pupil size.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR Area Under the Curve (0-12 s) - Blue Light

    Post-illumination pupillary responses (PIPR) to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR area under the curve (AUC) from 0 to 12 seconds captures the total magnitude and duration of the sustained post-illumination response. It is calculated as the integrated area in %.s.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR at 6 s - Red Light

    Post-illumination pupillary responses (PIPR) to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after red light offset. It is calculated as a percentage of baseline pupil size.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR Area Under the Curve - Red Light

    Post-illumination pupillary responses (PIPR) to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR area under the curve (AUC) from 0 to end of recording captures the total magnitude and duration of the sustained post-illumination response. It is calculated as the integrated area in %.s.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR at 6 s - Flash White Light

    Post-illumination pupillary responses (PIPR) to white light flash will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after white light offset. It is calculated as a percentage of baseline pupil size.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • PIPR at 6 s - Continuous White Light

    Post-illumination pupillary responses (PIPR) to continuous white light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. PIPR at 6 s is measured as pupil size at 6 seconds after white light offset. It is calculated as a percentage of baseline pupil size.

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

Secondary Outcomes (17)

  • Retinal Thickness

    Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Choroidal Thickness

    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

    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

    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

    Baseline (pre-intervention), 60 and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • +12 more secondary outcomes

Other Outcomes (8)

  • Breath Alcohol Concentration

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Peripheral Oxygen Saturation (SpO₂)

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • Pulse Rate

    Baseline (pre-intervention), 30, 60, 90, and 120 minutes post-intervention - during each of the 3 study visits (up to 3 study days total)

  • +5 more other outcomes

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants receive placebo tablets and non-active beverage under double-masked crossover conditions.

Other: Placebo Comparator: Placebo

Caffeine

EXPERIMENTAL

Participants receive caffeine administration under double-masked crossover conditions.

Other: Caffeine administration

Alcohol

EXPERIMENTAL

Participants receive alcohol administration under double-masked crossover conditions.

Other: Alcohol (Ethanol)

Interventions

Placebo Comparator: PlaceboOTHER

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.

Placebo
Caffeine administrationOTHER

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.

Caffeine
Alcohol (Ethanol)OTHER

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.

Alcohol

Eligibility Criteria

Age30 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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
  • \*CCQ: Caffeine Consumption Questionnaire
  • \*\*AUDIT-C: Alcohol Use Disorders Identification Test-C

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Singapore, 119276, Singapore

RECRUITING

Related Publications (6)

  • 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: 29023550BACKGROUND

  • 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: 27437402BACKGROUND

  • 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: 24325436BACKGROUND

  • 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: 32011181BACKGROUND

  • 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: 27983733BACKGROUND

  • 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: 30809186BACKGROUND

MeSH Terms

Interventions

Ethanol

Intervention Hierarchy (Ancestors)

AlcoholsOrganic Chemicals

Study Officials

  • Raymond P. Najjar, PhD

    Department of Ophthalmology, National University of Singapore (NUS)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Vicknaswari T, Bsc Optometry

CONTACT

+6565165459tv96@nus.edu.sg

Najiya S.K Meethal, PhD

CONTACT

+6591183642najiyaskmeethal@nus.edu.sg

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Masking is maintained through separation of study roles. The study team member responsible for preparing the intervention (caffeine, alcohol, or placebo) is not involved in participant assessments or data collection. Outcome assessors and investigators performing pupillometry, imaging, and physiological measurements remain blinded to the assigned condition. Participants are also masked to the intervention received, as all conditions are administered in identical-appearing tablet and beverage forms. The allocation sequence is held by an independent staff member not involved in outcome assessments.
Purpose
DIAGNOSTIC
Intervention Model
CROSSOVER
Model Details: In this study, the cross-over model refers to the way each participant experiences all three experimental conditions: caffeine, alcohol, and placebo. Each participant completes three separate study visits, with one condition administered per visit. The order of conditions is randomized. Some participants will start with caffeine, followed by alcohol and a placebo, while others will receive a different sequence. This randomization helps prevent order effects, such as changes in physiological responses due to learning, adaptation, or fatigue across repeated sessions on the observed results. Because each participant receives all three conditions, they act as their own control, allowing direct comparison of ocular and physiological responses across caffeine, alcohol, and placebo conditions.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

May 18, 2026

First Posted

June 4, 2026

Study Start

June 1, 2026

Primary Completion (Estimated)

May 5, 2027

Study Completion (Estimated)

November 5, 2027

Last Updated

June 4, 2026

Record last verified: 2026-05

Locations

SG(1)