Development of Countermeasures Against Adverse Metabolic Effects of Shift Work

The goal of this application is to determine whether changing the timing of food intake prevents the adverse metabolic effects of circadian misalignment.

Study Overview

• Status: Completed
• Conditions: Circadian Dysregulation
• Intervention / Treatment: Behavioral: Meal schedule

Detailed Description

Shift work is associated with circadian misalignment and an increased risk for the development diabetes, obesity, and cardiovascular disease. This research will determine whether changing the feeding schedule can prevent metabolic alterations that can lead to the abovementioned disorders. This research will provide mechanistic insight and may provide a novel therapeutic approach against the increased risk for diabetes, obesity, and cardiovascular disease among shift workers.

• Study Type: Interventional
• Enrollment (Actual): 20
• 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 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI between 18.5 and 29.9 kgm-2
• Healthy adults with regular sleep-wake timing
• Non-smokers
• Completion of medical and psychological screening tests
• Able to spend 14 consecutive days in the sleep laboratory

Exclusion Criteria:

• BMI <18.5 or > 29.9 kgm-2
• History of neurological or psychiatric disorder
• History of sleep disorder or regular use of sleep-promoting medication
• Current prescription, herbal, or over-the-counter medication use
• Traveling across 2 or more time zones within past 3 months
• Donating blood within past 8 weeks
• Worked night or rotating shift work within past 3 years
• Hearing impairment
• Drug or alcohol dependency

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; During Forced Desynchrony sleep and wake will occur at different circadian phases, while meals are restricted to the biological day.	Behavioral: Meal schedule
Other: Control; During Forced Desynchrony sleep and wake, as well as meals, will occur at different circadian phases.	Behavioral: Meal schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma leptin levels across sleep/wake cycle	Frequent blood samples	During circadian alignment (Day 7) and circadian misalignment (Day 10-11)
Change in circadian profile of plasma leptin	Frequent blood samples	During constant routine before forced desynchrony (Days 3-4) and constant routine after forced desynchrony (Days 12-13)
Change in glucose tolerance	Frequent blood samples before and after standardized meals	During circadian alignment (Day 7) and circadian misalignment (Day 10-11)
Change in circadian profile of plasma glucose levels	Frequent blood samples	During circadian alignment (Day 7) and circadian misalignment (Day 10-11)
Change in plasma insulin levels after standardized test meal	Frequent blood samples before and after standardized meals	During circadian alignment (Day 7) and circadian misalignment (Day 10-11)
Change in circadian profile of plasma insulin levels	Frequent blood samples	During circadian alignment (Day 7) and circadian misalignment (Day 10-11)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
o Change in circadian phase markers, such as from core body temperature, melatonin, and cortisol	Core temperature sensor throughout protocol, days 1-14. Frequent blood samples during constant routine before forced desynchrony (Days 3-4) and constant routine after forced desynchrony (Days 12-13)	Core temperature and frequent blood samples
Changes circadian rhythm in resting energy expenditure	Indirect calorimetry	During constant routine before forced desynchrony (Days 3-4) and constant routine after forced desynchrony (Days 12-13)
Change in hunger and appetite, mood, and cognitive performance	Subjective hunger ratings and cognitive tests performed via computer interface	Tests taken throughout the protocol, days 1-14
Changes in microbiota, gene expression, epigenetic or proteomic markers	Frequent blood samples and saliva samples	samples taken during forced desychrony (days 7-11) and the constant routine protocols (days 3-4 and 11-13)
Changes in sleep	Polysomnography	sleep periods following day 1, days 6-7 and days 10-11

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Frank A Scheer, PhD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Chellappa SL, Engen PA, Naqib A, Qian J, Vujovic N, Rahman N, Green SJ, Garaulet M, Keshavarzian A, Scheer FAJL. Proof-of-principle demonstration of endogenous circadian system and circadian misalignment effects on human oral microbiota. FASEB J. 2022 Jan;36(1):e22043. doi: 10.1096/fj.202101153R.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2015
• Primary Completion (Actual): August 29, 2018
• Study Completion (Actual): August 29, 2018

Study Registration Dates

• First Submitted: November 12, 2014
• First Submitted That Met QC Criteria: November 12, 2014
• First Posted (Estimate): November 17, 2014

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Circadian Misalignment, Forced Desynchrony, Metabolism, Meal-timing, Circadian
• Additional Relevant MeSH Terms: Nervous System Diseases; Chronobiology Disorders
• Other Study ID Numbers: R01HL118601 (U.S. NIH Grant/Contract)