NCT02202811

Brief Summary

The purpose of this study is to understand how behaviors and the effects of the body's internal clock (called the circadian pacemaker) affect the control of the heart and blood pressure. People with Obstructive Sleep Apnea (OSA) are hypothesized to have altered circadian amplitudes in certain key indices of cardiovascular (CV) and an abnormally advanced circadian phase in some of the same key indices of CV risk. The investigators hypothesize that such changes, taken together, may explain the different timing of heart attack and sudden cardiac death in OSA.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
39

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Aug 2014

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 17, 2014

Completed
12 days until next milestone

First Posted

Study publicly available on registry

July 29, 2014

Completed
3 days until next milestone

Study Start

First participant enrolled

August 1, 2014

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 9, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 9, 2020

Completed
Last Updated

July 2, 2025

Status Verified

June 1, 2025

Enrollment Period

5.6 years

First QC Date

July 17, 2014

Last Update Submit

June 27, 2025

Conditions

Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (30)

  • Primary dependent variable: Circadian rhythm amplitude of plasma epinephrine concentration

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of plasma epinephrine concentration during resting baseline conditions. Circadian rhythm amplitude will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of plasma epinephrine concentration

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian phase of plasma epinephrine concentration during resting baseline conditions. Circadian rhythm phase will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases and stated in relation to the reported habitual sleep time.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of plasma epinephrine reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma epinephrine concentration from resting baseline to end of 15 minutes of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of plasma epinephrine reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma epinephrine concentration from resting baseline to end of 15 minute of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of plasma epinephrine reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma epinephrine concentration from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of plasma epinephrine reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma epinephrine concentration from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of blood pressure (BP)

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of systolic and diastolic BP during resting baseline conditions. Circadian rhythm amplitude will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of blood pressure (BP)

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian phase of systolic and diastolic BP during resting baseline conditions. Circadian rhythm phase will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases and stated in relation to the reported habitual sleep time.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of blood pressure (BP) reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in systolic and diastolic BP from resting baseline to end of 15 minutes of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of blood pressure (BP) reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in systolic and diastolic BP from resting baseline to end of 15 minute of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of blood pressure (BP) reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in systolic and diastolic BP from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of blood pressure (BP) reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in systolic and diastolic BP from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of plasma cortisol concentration

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of plasma cortisol concentration during resting baseline conditions. Circadian rhythm amplitude will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of plasma cortisol concentration

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian phase of plasma cortisol concentration during resting baseline conditions. Circadian rhythm phase will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases and stated in relation to the reported habitual sleep time.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of plasma cortisol reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma cortisol concentration from resting baseline to end of 15 minutes of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of plasma cortisol reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma cortisol concentration from resting baseline to end of 15 minute of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of plasma cortisol reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma cortisol concentration from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of plasma cortisol reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in plasma cortisol concentration from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of heart rate

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of heart rate during resting baseline conditions. Circadian rhythm amplitude will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of heart rate

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian phase of heart rate during resting baseline conditions. Circadian rhythm phase will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases and stated in relation to the reported habitual sleep time.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of heart rate reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in heart rate from resting baseline to end of 15 minutes of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of heart rate reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in heart rate from resting baseline to end of 15 minute of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of heart rate reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in heart rate from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of heart rate reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in heart rate from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of cardiac vagal tone

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of cardiac vagal tone during resting baseline conditions. Circadian rhythm amplitude will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of cardiac vagal tone

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian phase of cardiac vagal tone during resting baseline conditions. Circadian rhythm phase will be assessed by cosinor analysis of all resting measurements obtained throughout the protocol assessed under constant conditions but at varied circadian phases and stated in relation to the reported habitual sleep time.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of cardiac vagal tone reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in cardiac vagal tone from resting baseline to end of 15 minutes of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of cardiac vagal tone reactivity to exercise

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in cardiac vagal tone from resting baseline to end of 15 minute of steady-state bicycle exercise. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by exercise obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm amplitude of cardiac vagal tone reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in cardiac vagal tone from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

  • Primary dependent variable: Circadian rhythm phase of cardiac vagal tone reactivity to change in posture

    Comparisons will be made between participants with obstructive sleep apnea (OSA) and healthy controls of the circadian amplitude of change in cardiac vagal tone from resting supine to end of 5 minutes of standing. Circadian rhythm amplitude of reactivity will be assessed by cosinor analysis of all changes induced by change in posture obtained throughout the protocol assessed under constant conditions but at varied circadian phases.

    Over 5 days

Secondary Outcomes (30)

  • Secondary dependent variable: Circadian rhythm amplitude of plasma tissue plasminogen activator inhibitor (tPA) concentration

    Over 5 days

  • Secondary dependent variable: Circadian rhythm phase of plasma tPA concentration

    Over 5 days

  • Secondary dependent variable: Circadian rhythm amplitude of plasma tPA reactivity to exercise

    Over 5 days

  • Secondary dependent variable: Circadian rhythm phase of plasma tPA reactivity to exercise

    Over 5 days

  • Secondary dependent variable: Circadian rhythm amplitude of plasma tPA reactivity to change in posture

    Over 5 days

  • +25 more secondary outcomes

Study Arms (2)

Obstructive Sleep Apnea

EXPERIMENTAL

Forced Desynchrony, OSA

Behavioral: Forced Desynchrony

Control

PLACEBO COMPARATOR

Forced Desynchrony, Control

Behavioral: Forced Desynchrony

Interventions

Forced DesynchronyBEHAVIORAL

all sleep opportunities and other activities will be scheduled by the experimenter so that by the end of the study these activities are spread evenly across all phases of the internal body clock.

ControlObstructive Sleep Apnea

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
* BMI less than 40 * Moderate to severe OSA (AHI)\>15 * No current or previous pharmacological treatment for hypertension

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (2)

  • Thosar SS, Bowles NP, Butler MP, McHill AW, Rice SPM, Emens JS, Shea SA. Endogenous Circadian System Attenuates Nighttime Vascular Endothelial Function in People With Untreated Obstructive Sleep Apnea. J Am Heart Assoc. 2025 Nov 18;14(22):e043596. doi: 10.1161/JAHA.125.043596. Epub 2025 Nov 6.

    PMID: 41195783DERIVED

  • Thosar SS, Berman AM, Herzig MX, McHill AW, Bowles NP, Swanson CM, Clemons NA, Butler MP, Clemons AA, Emens JS, Shea SA. Circadian Rhythm of Vascular Function in Midlife Adults. Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1203-1211. doi: 10.1161/ATVBAHA.119.312682.

    PMID: 31070470DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Condition Hierarchy (Ancestors)

Sleep Apnea SyndromesApneaRespiration DisordersRespiratory Tract DiseasesSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System Diseases

Study Officials

  • Steven A Shea, PhD

    Oregon Health and Science University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Saurabh S. Thosar, PhD

Study Record Dates

First Submitted

July 17, 2014

First Posted

July 29, 2014

Study Start

August 1, 2014

Primary Completion

March 9, 2020

Study Completion

March 9, 2020

Last Updated

July 2, 2025

Record last verified: 2025-06

Locations

US(1)