Countermeasures to Circadian Misalignment

Metabolic Disease Clinical Trial

— C2CM  

Official title:

Time-restricted Feeding to Mitigate Metabolic Impairments During Circadian Misalignment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04966351
• Other study ID #: 19-9666H
• Secondary ID: R01DK125653
• Status: Recruiting
• Phase: N/A
• Start date: July 7, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2023
• Source: Colorado State University
• Contact: Josiane L Broussard, PhD
• Phone: 9704913103
• Email: josiane.broussard[@]colostate.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Insufficient sleep and circadian misalignment are independent risk factors for the development of obesity and diabetes, yet few strategies exist to counter metabolic impairments when these behaviors are unavoidable.

This project will examine whether avoiding food intake during the biological night can mitigate the impact of circadian misalignment on metabolic homeostasis in adults during simulated night shift work. Findings from this study could identify a translatable strategy to minimize metabolic diseases in populations that include anyone working nonstandard hours such as police, paramedics, firefighters, military personnel, pilots, doctors and nurses, truck drivers, and individuals with sleep disorders.

Description:

People who work evening, night or rotating shifts (i.e. "nonstandard" work hours) represent one in five U.S. employees and are alarmingly 44% more likely to develop Type 2 diabetes (T2D) compared to people who work standard day shifts. Circadian misalignment is one mechanism suggested to increases the risk of obesity and diabetes in people who work non-standard hours, and is highly prevalent and often unavoidable in modern, 24-hour society (e.g. shift work, long work hours, jet lag, medical residency, emergency responders, military personnel, Daylight Savings Time changes, etc). Disruptions in sleep and circadian rhythms have been linked to insulin resistance, increased energy intake, weight gain, and increased total body, abdominal and intrahepatic fat content, yet there have been limited attempts at identifying strategies or countermeasures to prevent the impact of such disruption on T2D risk in a sizeable proportion of the population.

Therefore, the long-term goal is to identify and develop effective, behavioral countermeasures to combat the increased risk for metabolic diseases associated with sleep and circadian disruption when these behaviors are unavoidable. The overall objective for this project is to test the impact of time-restricted feeding to a 7h period in the day as a noninvasive countermeasure to the metabolic impairments associated with circadian misalignment. The central hypothesis is that time-restricted feeding to the daytime period will prevent metabolic impairments during circadian misalignment compared to a condition where energy is consumed throughout the day and night. The rationale for the proposed project is that defining a non-invasive, scalable and feasible countermeasure to circadian misalignment could mitigate the risk of obesity and T2D.

To test the overall hypothesis, a randomized crossover study will be used with a rigorous inpatient diet, activity and light-controlled protocol in healthy men and women. The impact of time restricted feeding during circadian misalignment on metabolic homeostasis will be determined.

Findings from this study represent a critical advancement in the fields of translational circadian and metabolic physiology by identifying and testing a countermeasure to circadian misalignment. Achievement of the proposed aims could lead to the development of new intervention strategies for chronic disease prevention and management. The knowledge to be gained offers the potential to support cost-effective programs that may inform healthcare approach to metabolic disease prevention in populations at risk for these diseases such as shift workers, individuals with sleep disorders and anyone who eats outside of daytime hours.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: June 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

1. 18-35 old; men and women; equal numbers of women and men will be included.

2. Body Mass Index (BMI) between 20.0 and 24.9 ("normal" weight).

3. Physical activity history: inactive to habitual moderate physical activity level

4. Sleep/wake history: habitual sleep duration between 7-9.25 hours.

5. Altitude history: Potential subjects must have lived at Denver altitude or higher for at least 3 months prior to inpatient stay.

Exclusion Criteria:

1. Any clinically significant medical, psychiatric, or sleep disorder

2. Use of prescribed medications/supplements/illicit drugs within one month prior to study

3. History of shift work in year prior to study, or travel more than one time zone in three weeks prior to study. [NOTE: Subjects can be studied at a later date.]

4. Women with history of prior gynecological pathology, <1 year post-partum, breast-feeding and/or pregnant.

5. Non-English speakers will be excluded, as we do not have access to a translator who could rely accurate information to the participant for the consent or throughout the study.

Related Conditions & MeSH terms

• Insulin Resistance
• Insulin Sensitivity
• Metabolic Disease
• Metabolic Diseases
• Sleep Disorders, Circadian Rhythm
• Sleep Wake Disorders

Intervention

Behavioral:
• Time-restricted feeding
Each subject will participate in both conditions (CM and CM+TRF)--one in which food is allowed during the nighttime period and one in which food will be restricted to the daytime only. Food intake will be matched across conditions and designed to keep participants weight stable.
• Circadian Misalignment
Healthy lean subjects will undergo circadian misalignment induced using a simulated night shift-work protocol in both conditions of the study. Each condition will last approximately 6 days.

Locations

Country	Name	City	State
United States	Colorado State University	Fort Collins	Colorado

Sponsors (4)

Lead Sponsor	Collaborator
Colorado State University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Salk Institute for Biological Studies, University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognitive assessments-Karolinska Sleepiness Scale	subjective sleepiness measurement 1-9, 1=Very Alert, 9=Very sleepy, great effort to keep awake, fighting sleep	Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Other	Cognitive assessments-Positive and Negative Affect Schedule	subjective emotions & feelings, Scores range from 10-50 with higher scores represent higher levels of positive affect of 20 emotions & feelings items, and lower scores represent lower levels of negative affect of 20 emotions & feelings items.	Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Other	Cognitive assessments- Psychomotor Vigilance Task	reaction time	Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Other	Cognitive assessments- Conjunction Visual Search Task	reaction time & error rate	Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Other	Sleep staging-assessed by polysomnography	Electrical activity across the scalp will be measured using polysomnography and sleep will be staged as Wake, Stage 1, Stage 2, Stage 3 and REM.	Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Other	Sleep quality assessments-assessed by Actiwatch	movement and light sensor equipment	Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Other	Sleep quality assessments-assessed by Maintenance of Wakefulness Test	onset of sleep latency	Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Other	Sleep quality assessments-assessed by Leeds Sleep Evaluation Questionnaire	subjective feelings of last night's sleep compared to usual of (1) getting to sleep- (easier, harder), (quicker, slower), (more drowsy, less drowsy); (2) quality of sleep- (more restful, less restful), (few periods of wakefulness, more periods of wakefulness); (3) awakening pattern-(easier, more difficult), (took shorter, took longer); (4) balance and coordination- (less clumsy, more clumsy)	Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Other	Functional grip strength-measured by hand dynamometer	average force	Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Other	Functional balance-assessed by multi-sensor recorder	gyroscope, accelerometer, attitude	Change to be assessed at Day 1, Day 3, Day 29, Day 31.
Other	Systolic and diastolic blood pressure	automatic vitals machine	Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Primary	Insulin sensitivity-derived from glucose tolerance test		Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Primary	Muscle tissue lipids-assessed by lipidomic analyses		Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Secondary	24-hour circulating blood glucose levels-assessed by assay		Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Secondary	24-hour circulating blood insulin levels-assessed by assay		Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Secondary	24-hour circulating blood free fatty acid levels-assessed by assay		Change to be assessed at Day 3, Day 5, Day 31, Day 33.

External Links

•   Josiane Broussard's Bibliography