Sleep, Light, Circadian, Central Oxidative Stress

Role of Ambien Lighting in Circadian Misalignment in a Chronic Variable Sleep Deficiency Paradigm: Impact on Sleep, Cognition, and Central Oxidative Stress

Irregular sleep timing and sleep deficiency are pervasive in society despite evidence that sleep deficiency impairs cognition and is linked to neurodegenerative disease. Potential pathways underlying the adverse cognitive function and brain health associated with irregular insufficient sleep include misalignment of sleep from the internal ~24-hour body clock and brain oxidative stress. This research will investigate these putative pathways and inform future interventions to mitigate the impact of sleep loss on cognition and brain health.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-visual Effects of Light; Chronic Variable Sleep Deficiency
• Intervention / Treatment: Behavioral: Dim Light; Behavioral: Control sleep; Behavioral: Chronic Variable Sleep Deficiency; Behavioral: Room light; Behavioral: Sleep- and Circadian-Informed Lighting

Detailed Description

Millions of adults in the US vary their day-to-day sleep timing to accommodate social and work demands. These irregular sleep schedules promote poor and insufficient sleep. Chronic insufficient sleep increases the risk of errors, accidents and developing various health disorders including neurodegenerative disease. The underlying mechanistic pathways by which irregular sleep schedules promote cognitive impairment and neurodegenerative disease remains poorly understood, and the proposed work will address this critical knowledge gap. Our preliminary data indicate that irregular sleep schedules induce circadian misalignment which we hypothesize is caused by irregular patterns of light exposure. Supporting this hypothesis, our pilot data show that implementing sleep- and circadian-informed lighting (SCIL) attenuated circadian misalignment and improved cognitive function, even in the presence of irregular sleep timing. Additionally, our pilot studies show that more sleep disturbance correlated with more oxidative stress (OS) in brain regions that are associated with cognitive function in humans, and consequently more OS in these regions correlated with poorer cognitive performance. Taken together, our results suggest that circadian misalignment and OS associated with insufficient sleep may be in the causal pathway for cognitive impairment due to irregular sleep schedules and SCIL may be a potential countermeasure. Therefore, the objective of this project is to determine the impact of chronic variable sleep deficiency (CVSD), as a model of irregular sleep schedules, on circadian misalignment, OS and cognition. Additionally, we will explore the role of ambient light exposure and the impact of SCIL conditions in a CVSD paradigm (2 cycles of two consecutive nights of 3 h of sleep followed by one 8-h recovery sleep) on neurophysiologic and neurocognitive outcomes. In a 7-night inpatient study, young healthy adults will be randomized to one of four conditions: dim-light control (8 h sleep each night), dim-light CVSD, room-light CVSD, and SCIL CVSD. The primary outcomes include circadian phase resetting, OS via central glutathione measured by magnetic resonance spectroscopy, and cognitive performance. The aims of the study are to: (1) Determine the causal role of light exposure in circadian phase resetting in CVSD, (2) evaluate the impact of SCIL in CVSD on circadian phase resetting, sleep and cognition, (3) evaluate the impact of sleep deficiency and circadian phase resetting in CVSD on OS, and (4) evaluate the association between cognition and central OS in CVSD. Our work will be a comprehensive evaluation of two mechanistic pathways - circadian misalignment and OS -that can contribute to cognitive impairment associated with irregular sleep schedules. We expect our experimental and analytic paradigm to be a foundational resource that can be extended to future studies examining mechanisms of cognitive impairment and neurodegenerative diseases associated with sleep loss and irregular sleep schedules, and have a positive public health impact by guiding therapeutic strategies for patients with sleep disorders and the general population at large who experience chronic variable sleep deficiency.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Leilah K Grant, PhD; Phone Number: 617-525-7118; Email: lgrant@bwh.harvard.edu
• Study Contact Backup: Name: Shadab A Rahman, PhD; Phone Number: 617-525-8830; Email: srahman@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy participants 18-40 years old.

Exclusion Criteria:

1. Volunteers must be drug-free (including caffeine, nicotine, and alcohol) for the entire duration of the study, with no history of drug or alcohol dependency.
2. Subjects must be free from any significant impairments of the visual system, including color blindness.
3. Subjects must be ambulatory, have no major visual or auditory handicaps, and be free from any major acute, chronic or debilitating medical conditions.
4. history of psychiatric illnesses or psychiatric disorders
5. History of consistent work during the overnight hours for the one year prior to study.
6. History of transmeridian travel >2 times zones, will require a 1 week wash out per hour of time difference from the Eastern Standard/Daylight Time zone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dim light control	Behavioral: Dim Light; <3 lux dim ambient lighting while awake; Behavioral: Control sleep; Nightly 8-h sleep opportunity
Experimental: Dim-light CVSD	Behavioral: Dim Light; <3 lux dim ambient lighting while awake; Behavioral: Chronic Variable Sleep Deficiency; Repeated cycles of sleep restriction followed by recovery sleep.
Experimental: Room-light CVSD	Behavioral: Chronic Variable Sleep Deficiency; Repeated cycles of sleep restriction followed by recovery sleep.; Behavioral: Room light; ~90 lux ambient lighting while awake
Experimental: SCIL CVSD	Behavioral: Chronic Variable Sleep Deficiency; Repeated cycles of sleep restriction followed by recovery sleep.; Behavioral: Sleep- and Circadian-Informed Lighting; Ambient visible light exposure with modulated intensity and spectrum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
circadian phase shifts in melatonin sulfate rhythm	Baseline: Day 1 of study, Final: Day 8 of study
Accuracy on the matrix reasoning task	Daily over 8 days throughout study intervention
WASO on the PSG	Baseline sleep, first short sleep, second short sleep.
MRS-derived GSH in the mPFC	Baseline: Day 1 of study, Final: Day 8 of study

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Sleep; Oxidative Stress; Light exposure; Circadian
• Additional Relevant MeSH Terms: Musculoskeletal and Neural Physiological Phenomena; Nervous System Physiological Phenomena; Sleep
• Other Study ID Numbers: 2025-P-001806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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