The Microbiome and Resilience to Sleep and Circadian Disruption

Stress Clinical Trial

Official title:

The Microbiome and Responsiveness to Stress: Countermeasure Strategies for Improving Resilience to Sleep and Circadian Disruption (Experiments 1 & 2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03747367
• Other study ID #: 15-0282
• Status: Recruiting
• Phase: N/A
• Start date: October 21, 2015
• Est. completion date: September 2021

Study information

• Verified date: October 2020
• Source: University of Colorado, Boulder
• Contact: Sleep and Chronobiology Laboratory
• Phone: 303 735 1923
• Email: sleep.study[@]colorado.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is about how sleep loss and being awake at night impacts the ability to think, changes molecules in the blood, and alters the bacteria that live in the gut that typically help keep people healthy. This work will have important implications for the development of treatments and countermeasures for people who do not sleep enough and need to be active at different times of the day and night (e.g., emergency workers and military personnel).

Description:

Experiment 1: Consistency of microbiota-gut-brain axis responses

Prior to the start of this study, there are screening procedures to ensure participants meet the criteria for the study. At the first consent screening appointment, participants will learn more about the study, answer questionnaires, and complete a psychological interview. At the second medical screening appointment, participants will have a physical exam, blood work, drug screen, pregnancy test, electrocardiogram (a measurement of heart activity), and a resting metabolic rate assessment (a measurement of how much energy the body uses at rest). Participants will also meet with a nutritionist to discuss their food preferences for the study. Although participants are not financially compensated for the screening procedures, the expense of the screening tests is covered and copies are provided to the participant upon request. All of the results of the screening procedures are confidential and will only be used by the study staff to determine eligibility for the study.

Following the screening procedures, participants will complete two laboratory visits, both visits preceded by two weeks of home activity monitoring. During the home monitoring, participants wear a special watch that records activity levels. Participants also keep a sleep/wake log and use a website to log their daily sleep/wake times (if participants cannot access this website, they can call into an answering machine to inform investigators when they go to bed and wake up each day). The investigators will provide participants with a pre-study diet prepared by study dieticians for participants to eat for the three days prior to the laboratory visit. During the two weeks between the first and second laboratory visit participants will continue to wear the special watch, keep a sleep/wake log, and use a website to log their daily sleep/wake times (or call them into the answering machine). Participants will again be given a pre-study diet for the three days prior to their second visit.

During the laboratory visits, participants will live in the Sleep and Chronobiology Lab at the University of Colorado at Boulder for 3.7 days on two different occasions. The day before the inpatient visit begins, participants will spend the night in the laboratory, sleeping their normal 8 hours. This will be used as a pre-study screening for problems with sleep. In the morning participants will complete some pre-study tests and samples which will take approximately 60 minutes. Participants will then be permitted to leave the laboratory and in the evening they will return to begin the study. During the study participants sleep schedule will be changed to simulate the sleep loss that emergency workers in medical and military situations experience. Participants will be given an initial 3 hour sleep opportunity and then kept awake overnight. Throughout the study participants will be given a 3 hour sleep opportunity for every 24 hours of the laboratory visit. While participants are awake, they will be asked to perform a number of computer tasks, including a driving simulator. Blood and saliva samples will be taken to test for circadian and metabolic markers. Participants will also be asked to collect samples of the bacteria that live in their gastrointestinal tract from used bathroom tissue after they use the bathroom in the study. Finally, investigators will test how the heart and nervous system respond to stress by having participants place their hand in an ice water bath. At the end of the laboratory visit participants will be given an 11 hour sleep opportunity to recover from their sleep loss. After 3 more days of recovery sleep and another 2 weeks of home monitoring (identical to the first two weeks of the study), these procedures will be repeated in a second laboratory visit.

Experiment 2: Pre-biotic

Methods for experiment 2 are exactly the same as experiment 1 with the following addition:

During the two weeks prior to laboratory visits, half of the study participants will be randomized (e.g., flip of a coin) to receive the prebiotic combination of polydextrose (PDX) and galacto-oligosaccharides (GOS) daily for 2 weeks and then tested in the first in-laboratory visit. These participants will then receive a maltodextrin placebo (a starch-derived food additive commonly used as a filling agent in a range of commercial foods and beverages) the two weeks prior to the second in-laboratory visit. The other half of participants will first receive maltodextrin and then the prebiotic diet. Investigators will provide participants the prebiotics and maltodextrin powders to be mixed in water and consumed each morning. The order in which participants receive the prebiotic diet will be maintained by the Clinical and Translational Research Center pharmacist. Neither the investigators nor participants will know what is in the powder provided.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Healthy

• Currently residing at Denver altitude or higher

Exclusion Criteria:

• Current major medical disorder

Related Conditions & MeSH terms

• Chronobiology Disorders
• Circadian Dysregulation
• Sleep Deprivation
• Stress

Intervention

Behavioral:
• Insufficient Sleep

Locations

Country	Name	City	State
United States	Sleep and Chronobiology Laboratory	Boulder	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
University of Colorado, Boulder	Office of Naval Research (ONR), University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in fecal microbiome	Fecal "beta diversity" (unit=weighted UniFrac)	Daily fecal samples while living in laboratory (3 samples per visit, 2 laboratory visits as part of a 39 day protocol)
Primary	Change in fecal metabolome	Fecal small molecules (Mass spect metabolite abundance)	Daily fecal samples while living in laboratory (3 samples per visit, 2 laboratory visits as part of a 39 day protocol)
Secondary	Visual Search Performance	Cognitive Throughput (items/minute)	Assessed every 3 hours daily while living in the laboratory (17 times per visit, 2 laboratory visits as part of a 39 day protocol)
Secondary	Maintenance of wakefulness test	Average latency to falling asleep (minutes)	Assessed every 3 hours daily while living in the laboratory (17 times per visit, 2 laboratory visits as part of a 39 day protocol)
Secondary	Karolinska Sleepiness Scale	Single question likert scale: Total score reported with a range of 1-9; min score=1[very alert], maximum score=9[very sleepy, great effort to keep awake, fighting sleep]. A higher score representing higher sleepiness. A lower score represents less sleepiness and a better outcome.	Assessed every 3 hours daily while living in the laboratory (17 times per visit, 2 laboratory visits as part of a 39 day protocol)
Secondary	Changes in plasma metabolome	Plasma small molecules (Mass spect metabolite abundance)	Assessed ~every 6 hours while living in the laboratory (10 times per visit, 2 laboratory visits as part of a 39 day protocol)