Biomarkers for Peripheral Circadian Clocks in Humans

The purpose of this project is to improve our understanding of peripheral circadian rhythms in humans. Circadian clocks are present in most tissues of the body with importance for optimal physiological function, health, and behavior. This project will utilize simulated jetlag protocols to systematically test novel hypotheses about the regulation of peripheral circadian rhythms in humans. Specifically, we will examine how changes in the time of when we are exposed to light and the timing of when we eat impacts proteins in the blood and saliva that represent rhythms from clocks in the brain (e.g., rhythms of the hormones melatonin and cortisol coordinated by the brain) and rhythms from clocks in body tissues (e.g., proteins made by immune and bone cells, and cells in the stomach and liver). We also aim to discover new blood-based biomarkers of peripheral rhythms in humans. We anticipate our findings will be the first step in developing novel circadian based treatments for aligning peripheral clocks under conditions such as jetlag, and for developing novel circadian biomarkers that will advance our scientific understanding of circadian rhythms.

Study Overview

• Status: Recruiting
• Conditions: Circadian Rhythms
• Intervention / Treatment: Behavioral: Simulated jetlag protocol

Detailed Description

Visit 1: Participants who meet pre-screen/initial inclusion criteria will be consented at Visit 1, complete additional questionnaires and interviews to assess inclusion/exclusion criteria, and we will collect descriptive data as well as have our clinical psychologist perform a clinical interview.

Visit 2: Participants will undergo medical screening at the Clinical Translational Research Center at the University of Colorado Boulder (UCB-CTRC) to determine health status.

Visits 3 & 6: Participants will be asked to maintain a regular ~8h sleep-wake schedule for two weeks prior to Visits 5 and 8. Participants will wear a wrist activity, skin temperature, and light exposure recorder. Participants will be asked to remain in the local time zone during ambulatory recording procedures and be asked to keep their typical schedules (e.g., not stay up all night for work or social events and not reside in a new place different from their place of residence).

Visit 4 & 7: Participants will come to the laboratory on days 11 and 39, where qualified staff will apply a Continuous Glucose Monitoring (CGM) sensor to be worn for ~3 days at home and will continue in the laboratory. For the three days leading up to the study isocaloric meals including breakfast, lunch, and dinner will be provided. Participants will be asked to consume these energy balanced research diets (no caffeine) and meal timing will be scheduled (breakfast ~30 min, lunch ~5h, and dinner ~10h after awakening,). Exercise will be proscribed for these 3-days prior to the in-lab study.

Visits 5 & 8: Participants will be randomized to condition order using an ABBA design (i.e., randomized into one of the two experimental conditions first in a crossover design: 3-days bright light exposure or 3-days of earlier timed meals). Both conditions are tested under an advanced sleep-wake schedule equivalent to traveling 5 time zones east. All participants will complete both conditions. On the second visit, participants will be tested in the other condition. Participants will live in the laboratory for 7.7 days each visit.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kenneth Wright, PhD; Phone Number: 303-735-1923; Email: sleep.study@colorado.edu

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80303
      • Recruiting
      • Sleep and Chronobiology Laboratory
      • Contact: Kenneth Wright; Phone Number: 303-735-1923; Email: sleep.study@colorado.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1) 17-35 years old 2) English speaking 3) Healthy 5) Altitude history: Currently residing at Denver altitude or higher

Exclusion Criteria:

1. Any medical, psychiatric, or sleep disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Meal timing; Three days of meals, bedtimes and wake times scheduled to occur 5h earlier.	Behavioral: Simulated jetlag protocol; 16 hours of wakefulness and an 8 hour scheduled sleep opportunity in a simulated jetlag protocol where you will go to bed and awaken earlier than usual.
Experimental: Bright light; Three days of exposure to bright light of ~3,000 lux, which is less than one-third the brightness of a sunrise or sunset (timed to start earlier by 1h each day) with scheduled bed and wake times timed 5h earlier.	Behavioral: Simulated jetlag protocol; 16 hours of wakefulness and an 8 hour scheduled sleep opportunity in a simulated jetlag protocol where you will go to bed and awaken earlier than usual.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PYY	Appetitive hormone-promotes satiety	hourly for up to 25 hours on two occasions
Ghrelin	Appetitive hormone-promotes food intake	hourly for up to 25 hours on two occasions
Leptin	Appetitive hormone-promotes satiety	hourly for up to 25 hours on two occasions
CRP	Acute phase response/also marker of inflammation	hourly for up to 25 hours on two occasions
OMD	Biomineralization	hourly for up to 25 hours on two occasions
PAI-1	Inhibitor of fibrinolysis	hourly for up to 25 hours on two occasions
IgE	Immune responses to parasites and allergens	hourly for up to 25 hours on two occasions
CCL18	Chemotaxis / immune cell trafficking	hourly for up to 25 hours on two occasions
PTH	Serum calcium homeostasis	hourly for up to 25 hours on two occasions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose	Blood sugar	continuously for up to 35 hours on two occasions
Insulin	hormone that helps regulated blood glucose levels	hourly for up to 25 hours on two occasions
Proteomics	proteins	hourly for up to 25 hours on two occasions

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Melatonin	Primary marker of the SCN master clock - high levels represent biological night	hourly for up to 25 hours on two occasions
Cortisol	Secondary marker of the SCN master clock - rising/high levels represent biological night	hourly for up to 25 hours on two occasions
Core body temperature	Secondary marker of the SCN master clock - low levels represent biological night	continuously for up to 35 hours on two occasions
Skin temperature	Secondary marker of the SCN master clock - high levels represent biological night	continuously for up to 35 hours on two occasions
Cognition	Measures of performance	hourly for up to 35 hours on two occasions
Blood pressure	systolic and diastolic pressures	hourly for up to 35 hours on two occasions
Metabolomics (grant application planned to analyze not currently funded)	small molecules in the plasma	hourly for up to 25 hours on two occasions
Oral microbiome (grant application planned to analyze not currently funded)	oral bacteria	hourly for up to 25 hours on two occasions
Skin microbiome (grant application planned to analyze not currently funded)	skin bacteria	hourly for up to 25 hours on two occasions

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Estimated): March 6, 2024

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 22-0466

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 de-identified.

Other data that is presented in a peer reviewed journal will be archived indefinitely and made available upon request.

Microbiome data will be deposited in the International Nucleotide Sequence Database Collaboration www.insdc.org/ and is already deposited in Qiita http://qiita.microbio.me

Metabolomics data will be deposited in Global Natural Products Social (GNPS) molecular networking http://gnps.ucsd.edu

• IPD Sharing Time Frame: Upon publication, microbiome data to be deposited permanently in International Nucleotide Sequence Database Collaboration www.insdc.org/ Data deposited in Qiita http://qiita.microbio.me Upon publication, proteomics and metabolomics data to be deposited and made freely available (e.g., https://figshare.com, http://gnps.ucsd.edu)
• IPD Sharing Access Criteria: microbiome, proteomics and metabolomics data will be freely available at www.insdc.org/, https://figshare.com, and http://gnps.ucsd.edu

Drug and device information, study documents

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