Biomarkers of Increased Free Living Sleep Time

Biomarkers and Altered Metabolic Pathways During Sleep Loss

This protocol will increase sleep duration in participants who maintain less than 6 hours sleep per night, to target the recommended 7 hours of sleep per night. The focus of this study is determine how increasing nightly sleep duration in these individuals who maintain less than 6 hours sleep per night changes their plasma metabolome and insulin sensitivity. The primary outcome will examine changes in branched-chain amino acids and the secondary outcome will examine changes in insulin sensitivity. The investigators will also determine if changes in plasma metabolites can be used as a biomarker to discriminate between adequate versus insufficient sleep.

Study Overview

• Status: Recruiting
• Conditions: Sleep Wake Disorders; Sleep Deprivation; Insufficient Sleep Syndrome
• Intervention / Treatment: Behavioral: Increased sleep duration

Detailed Description

Impaired sleep affects millions of people each year representing an important public health issue. This project will utilize metabolomics approaches to identify potential mechanisms underlying increased cardiometabolic risk associated with insufficient sleep and to identify potential biomarkers in the blood that respond to insufficient sleep. Investigators will conduct a controlled in-laboratory insufficient protocol where participants will sleep in the lab for one night with sleep timing based on their habitual insufficient sleep schedule. In the morning, plasma will be collected for metabolomics analyses and participants will complete an oral glucose tolerance test for insulin sensitivity analyses. Participants will then complete a 4 -week increased sleep duration intervention targeting the recommended 7 hours of sleep per night. Following this intervention participants will again sleep in the lab for one night on their new sleep schedule. In the morning, plasma will be collected for metabolomics analyses and participants will complete an oral glucose tolerance test for insulin sensitivity analyses. Investigators anticipate these findings will be the first step in developing biomarkers of impaired sleep under free-living sleep conditions, and to determine how such biomarkers relate to insulin sensitivity changes associated with sleep loss.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher Depner; Phone Number: 303-735-1923; Email: christopher.depner@utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Recruiting
      • Sleep Wake Center--University of Utah
      • Contact: Christopher Depner; Phone Number: 801-581-2275; Email: sleepstudyparticipant@utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 18-35 years old; men and women

   a. Equal numbers of women and men will be included.

2. Body Mass Index (BMI) of > 18.5 and <24.9.
3. Inactive to habitual moderate physical activity level (<5 days of exercise per week).
4. Sleep/wake history: habitual sleep duration less than 6 hours per night.
5. Altitude history: Potential participants must have lived at Denver altitude or higher for at least 3 months.

Exclusion Criteria:

1. Any clinically significant unstable medical or surgical condition within the last year (treated or untreated).
2. Any clinically significant psychiatric condition, as defined by DSM-IV-TR. I
3. Any clinically significant sleep disorder.
4. Use of prescription medications/supplements within one month or need of these medications at any time during the study.
5. Symptoms of active illness (e.g., fever).
6. Uncorrected visual impairment
7. History of shift work in prior year or travel more than one time zone in three weeks prior to study.
8. Participants must be entirely drug-free of illicit drugs, medications, nicotine and herbal products for one month prior to study.
9. Blood donation in the 30 days prior to inpatient study.
10. Ovulating women will be selected on the basis of a history of regular menstrual cycle ranging in length from 25-32 days with a maximum of three days variation month-to-month. They will have no history of prior gynecological pathology, be at least 1 year post-partum, not breast-feeding and not pregnant (HCG pregnancy test at screening and upon admission to the inpatient protocol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Increased Sleep Duration Intervention; Following baseline assessments, participants will complete a 4-week increased sleep duration intervention followed by one night of sleep in the lab on this increased sleep duration schedule. In the morning, participants will have blood collected for metabolomics analyses and complete oral glucose tolerance testing	Behavioral: Increased sleep duration; Participants will increase their nightly time in bed by 2 hours per night for 4 weeks to target the recommended 7 hours of sleep per night.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics-branched chain amino acids change from baseline	Investigators will measure the abundance of the branched chain amino acids (valine, leucine, isoleucine) in plasma at baseline and at post intervention.	Morning fasted blood will be collected for analyses at baseline and after the four week increased sleep duration intervention.
Insulin Sensitivity change from baseline	Investigators will measure insulin sensitivity using the oral glucose tolerance test in the morning after overnight sleep assessments in the lab, at baseline and after the four week increased sleep duration intervention.	Oral glucose tolerance testing will take about 3 hours to complete, and will be tested at baseline and after the four week increased sleep duration intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Untargeted Metabolomics change from baseline	Investigators can detect relative abundance of ~4,000 plasma metabolites. A combination of metabolites that can discriminate between adequate versus insufficient sleep will be identified as a potential biomarkers of insufficient sleep in free-living adults.	Morning fasted blood will be collected for analyses at baseline and after the four week increased sleep duration intervention.

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: University of Colorado, Boulder
• Investigators: Principal Investigator: Christopher Depner, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2019
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 26, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Neurologic Manifestations; Sleep Wake Disorders; Sleep Deprivation
• Other Study ID Numbers: 133959

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Any data generated from the proposed work that is presented in a peer reviewed journal will be uploaded, de-identified, into the Metabolomics Data Repository and Coordinating Center (DRCC) (U01) through UCSD; http://www.metabolomicsworkbench.org/nihmetabolomics/datasharing.html. In addition, .raw data that is presented in a peer reviewed journal will be archived indefinitely and made available upon request.
• IPD Sharing Time Frame: Data will become available upon publication in peer-reviewed journals and will be made available indefinitely.
• IPD Sharing Access Criteria: Active membership and username are required to access the raw metabolomics data on Metabolomics Workbench.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No