Impact of Sex and Age on Non-visual Light Input That Affects Sleep and Circadian Rhythms

The goal of this clinical trial is to learn how the pupil responds to different light stimuli and how that relates to sleep and daily rhythms in healthy people of different ages.

The main questions it aims to answer are:

• Does the eye's pupil response to light stimuli differ by the sex and age of the participant?
• Is the eye's pupil response to light stimuli related to each participant's sleep timing, their body clock timing, and their hormone responses to light.

Participants will have a special eye exam and complete questionnaires before starting the study to see if they can participate. If they can participate, they will wear a special watch that monitors their activity and light levels for one week. Then they will live in a research room at the Mass General Hospital for 3 days/2 nights during which we will test their pupil response to light, their body clock timing, and their hormone responses to light.

Study Overview

• Status: Recruiting
• Conditions: Normal Physiology
• Intervention / Treatment: Device: Pupillometry; Device: Light box exposure

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth B Klerman, MD PhD; Phone Number: 617-643-2424; Email: ebklerman@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Elizabeth Klerman, MD PhD; Phone Number: 617-726-5199; Email: mgh_pulsar_study@mgb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• (i) 18-85 years old.
• (ii) Habitual sleep onset 10 pm- 1 am;
• (iii) Habitual wake onset 5:30 am- 8:30 am;
• (iv) vision correctable to 20/30;
• (v) stable medically.
• (vi) ability to speak, understand, and read English at a high school level

Exclusion Criteria:

• (i) Color blind by Ishihara Color Blindness Test;
• (ii) any history of eye trauma, surgery or abnormality (e.g., retinopathy, glaucoma, cataracts, amblyopia, macular degeneration, congenital color vision deficiencies, or any type of blindness) besides correctable vision abnormalities (e.g., with glasses); any abnormalities on clinical eye exam (e.g., neuritis, Neuromyelitis optica, treated or untreated glaucoma) such that the ophthalmologist recommends the participant not be studied; Limited cataracts (e.g., Lens Opacities Classification (LOCS) III grade <2) will be allowed and documented during the eye exam. Eye drops that affect pupil size or contractility (e.g. mydriatics, miotics); drops to treat glaucoma (e.g., pilocarpine, brimonidine, other drops like artificial tear drops, or anti-inflammatory drops would not be exclusionary)
• (iii) current or history of neurologic or psychiatric disease including autonomic function disorder or migraines; psychiatric disorder requiring medications in a first degree relative; limited-duration counseling without prescription medications will not be exclusionary; (iv) current or history of circadian rhythm sleep-wake disorder;
• (v) prescription or non-prescription drugs affecting the pupil (e.g., affecting autonomic function), sleep, melatonin (e.g., lithium, alpha- and beta-adrenergic antagonists), and/or circadian rhythms (e.g., beta blockers, non-steroidal anti-inflammatory drugs, tricyclics);
• (vi) Other disorders that can affect or may be affected by intrinsically photosensitive Retinal Ganglion Cell (ipRGC) function, including diabetes mellitus, multiple sclerosis, Parkinson's disease, seasonal affective disorder;
• (vii) shift- or night-work in past three months; history of night work in preceding 3 year period
• (viii) crossing more than 2 time zones in past three months;
• (ix) presence of depression as assessed by a Beck Depression Inventory (BDI) score >14.
• (x) pregnant or less than 6 weeks post-partum or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Testing non-visual light impacts on pupil response, circadian timing, and hormones; Pupillometry on day 1 in afternoon and evening and on day 2 in morning and evening. Participants will be randomized to one of 8 different light stimuli within the pupillometry; Red light exposure on night 1 to determine circadian timing; Blue/green light exposure on night 2 to compare hormone response during blue/green light to that during red light on night 1

Device: Pupillometry; Pupillometer measurement of pupil size in response to different light stimuli; Device: Light box exposure; Using a light box to produce different wavelengths and intensities of light. Exposure to red light on Night 1 and blue/green light on Night 2 to determine circadian timing and suppression of hormone (melatonin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil size	Pupil size as measured by pupillometry	During pupillometry testing on Day 1 afternoon, Day 1 evening, Day 2 morning, Day 2 evening
Melatonin levels for circadian timing assessment	Melatonin levels from saliva collection during Night 1 light box red light exposure	Night 1
Melatonin levels for hormone response	Melatonin levels from saliva collection during Night 2 light box blue/green light exposure compared to those during Night 1 light box red light exposure	Night 1 and Night 2

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Elizabeth B Klerman, MD PhD, Mass. General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 2, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: melatonin; light; circadian rhythms; eye pupil response
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 2023P000904

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing will be conducted per National Institutes of Health (NIH) and MassGeneralBrigham (MGB) policies and regulations. Only de-identified data will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No