Role of Photic and Non-photic Time Cues in Resetting Circadian Rhythms (LipidPRC)

Determining the Role of Photic and Non-photic Time Cues in Resetting Circadian Rhythms in Humans

The aim of this study is to determine the principal time cue (light or meals) for resetting circadian rhythms in melatonin and metabolic outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Light Exposure; Meal Timing
• Intervention / Treatment: Behavioral: Bright Light; Behavioral: 12-h meal window; Behavioral: Time-restricted eating; Behavioral: Dim light

Detailed Description

The objective of this proposal is to construct and compare PRCs describing the relationship between the timing of light exposure and meals across the 24-hour day and the size and direction of shift in circadian rhythms of circulating lipids and melatonin in humans. Completion of the work will provide mechanistic insight on the role of photic and non-photic cues mediating entrainment of circadian rhythms in humans besides that of melatonin. In this proposal, we will use the same experimental paradigm that we have successfully used previously to characterize and compare PRCs for shifts in melatonin in response to light exposure of different durations and spectra, and as used in our pilot trials demonstrating a robust PRC of lipid circadian rhythms in response to combined photic and non-photic stimuli across the day. We will achieve our objective using a randomized controlled trial in young healthy adults (n=48, 18-30 years) that systematically manipulates the timing of 6.5-hour bright light exposure and 6.5-hour time restricted eating across the 24-hour circadian cycle to specifically:

Aim 1: Determine if light is the primary time cue for resetting melatonin but not lipid circadian rhythms. Hypothesis: The resetting response of circadian rhythms in melatonin but not cholesterol and triglycerides is dependent upon the circadian phase at which a 6.5-hour bright light exposure occurs.

Aim 2: Determine if meal timing is the primary time cue for resetting lipid but not melatonin circadian rhythms. Hypothesis: The resetting response of circadian rhythms in cholesterol and triglycerides but not melatonin is dependent upon the circadian phase at which a 6.5-hour time restricted eating occurs.

Aim 3 (Exploratory): Evaluate the acute effects of eating across the 24-hour day on circulating lipid levels. Hypothesis: The acute effects of 6.5-hour time restricted eating on circulating cholesterol and triglycerides levels are dependent on the circadian phase at which meals are eaten.

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

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged between 18-30 years
• Healthy (no medical, psychiatric or sleep disorders;
• Non-smoking for at least 6 months;
• Body Mass Index of >18 or <30 kg/m2;
• Able to maintain 8-hour consistent sleep schedule during the study
• Able to refrain from caffeine, alcohol, medication and supplements during the study

Exclusion Criteria:

• History of alcohol or substance abuse;
• Positive result on drugs of abuse urine toxicology;
• Current or past history of sleep disorders, including but not limited to obstructive sleep apnea, narcolepsy, insomnia, or any significant sleep complaint
• Psychiatric disorder, or first degree relative with a psychiatric disorder
• Recent acute or chronic medical disorder
• Use of drugs or medication (birth control OK) likely to affect sleep, alertness or light sensitivity, as determined by the investigators
• Visual disorder, including but not limited to color blindness, or family history of glaucoma
• Pregnancy or lactation
• Shift work (past 3 years)
• Transmeridian travel (2 or more time zones) in the past 3 months
• Any other reason as determine by the Principal Investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bright light; Participants will receive a 6.5-hour 10,000 lux light pulse (4100K fluorescent light) centered within the 16-hour wake episode (start 4.75 hour after wake and end 11.25 hour after wake). Participants will receive 4 identical meals (equal calories and macronutrient content), over a 12-hour interval (meals at 2, 6, 10, and 14 hours after waking) centered within the 16-hour wake episode.	Behavioral: Bright Light; 6.5-hour 10,000 lux light pulse (4100K fluorescent light) centered within the 16-hour wake episode (start 4.75 hour after wake and end 11.25 hour after wake).; Behavioral: 12-h meal window; 12-hour restricted meal window (4 meals at 2, 6, 10, and 14 hours after waking) centered within the 16-hour wake episode.
Experimental: Time-restricted eating; Participants will consume 4 identical meals, as in the other groups, except that the meal window will be restricted to 6.5 hours instead of 12 hours (meals at 4.75, 6.9, 9.1, 11.25 hours after waking) centered within the 16-hour wake episode. Participants will remain in dim light (<3 lux) throughout the 16-hour wake episode.	Behavioral: Time-restricted eating; 6.5-hour restricted meal window (4 meals at 4.75, 6.9, 9.1, 11.25 hours after waking) centered within the 16-hour wake episode.; Behavioral: Dim light; dim light (<3 lux) throughout the 16-hour wake episode
Sham Comparator: Control; Participants will receive 4 identical meals (equal calories and macronutrient content), over a 12-hour interval (meals at 2, 6, 10, and 14 hours after waking) centered within the 16-hour wake episode. Participants will remain in dim light (<3 lux) throughout the 16-hour wake episode.	Behavioral: 12-h meal window; 12-hour restricted meal window (4 meals at 2, 6, 10, and 14 hours after waking) centered within the 16-hour wake episode.; Behavioral: Dim light; dim light (<3 lux) throughout the 16-hour wake episode

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amplitude of Phase Response Curve of melatonin	Amplitude of phase response curve of melatonin derived by fitting a sinusoidal regression to the individual phase shift data across ~24 hours	24 hours
Amplitude of Phase Response Curve of triglyceride	Amplitude of phase response curve of triglyceride derived by fitting a sinusoidal regression to the individual phase shift data across ~24 hours	24 hours
Amplitude of Phase Response Curve of cholesterol	Amplitude of phase response curve of cholesterol derived by fitting a sinusoidal regression to the individual phase shift data across ~24 hours	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of melatonin	AUC of melatonin	6.5 hours during intervention
Area under the curve (AUC) of triglyceride	AUC of triglyceride	6.5 hours during intervention
Area under the curve (AUC) of cholesterol	AUC of cholesterol	6.5 hours during intervention

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2022
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 11, 2022

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

• Other Study ID Numbers: 2021P000757

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
• product manufactured in and exported from the U.S.: No