Clinical trial NCT04966351: Countermeasures to Circadian Misalignment
Official title: Time-restricted Feeding to Mitigate Metabolic Impairments During Circadian Misalignment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Circadian Rhythm Sleep Disorder of Shift Work Type
Metabolic Disease
Insulin Sensitivity
Keywords: Shift work
Sleep
Blood sugar
Metabolism
Lead sponsor: Colorado State University
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
name: Salk Institute for Biological Studies
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-07-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Insulin sensitivity-derived from glucose tolerance test
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: Muscle tissue lipids-assessed by lipidomic analyses
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Secondary outcomes:
measure: 24-hour circulating blood glucose levels-assessed by assay
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: 24-hour circulating blood insulin levels-assessed by assay
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: 24-hour circulating blood free fatty acid levels-assessed by assay
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
Other outcomes:
measure: Cognitive assessments-Karolinska Sleepiness Scale
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: Cognitive assessments-Positive and Negative Affect Schedule
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: Cognitive assessments- Psychomotor Vigilance Task
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: Cognitive assessments- Conjunction Visual Search Task
timeFrame: Change to be assessed at Day 3, Day 5, Day 31, Day 33.
measure: Sleep staging-assessed by polysomnography
timeFrame: Change to be assessed at Day 2, Day 4, Day 30, Day 32.
measure: Sleep quality assessments-assessed by Actiwatch
timeFrame: Change to be assessed at Day 2, Day 4, Day 30, Day 32.
measure: Sleep quality assessments-assessed by Maintenance of Wakefulness Test
timeFrame: Change to be assessed at Day 2, Day 4, Day 30, Day 32.
measure: Sleep quality assessments-assessed by Leeds Sleep Evaluation Questionnaire
timeFrame: Change to be assessed at Day 2, Day 4, Day 30, Day 32.
measure: Functional grip strength-measured by hand dynamometer
timeFrame: Change to be assessed at Day 2, Day 4, Day 30, Day 32.
measure: Functional balance-assessed by multi-sensor recorder
timeFrame: Change to be assessed at Day 1, Day 3, Day 29, Day 31.
measure: Systolic and diastolic blood pressure
timeFrame: Change to be assessed at Day 2, Day 4, Day 30, Day 32.
Locations:
city: Fort Collins
country: United States
facility: Colorado State University
state: Colorado
Study officials:
References: