Phenotypic and Genotypic Markers of Performance Vulnerability to Sleep Loss

Insufficient sleep is common, affecting 20-40% of adults, and resulting from sleep disorders, medical conditions, work demands, stress/emotional distress, and social/domestic responsibilities. It produces significant social, financial and health-related costs, and it has increasingly become a major public health concern as population studies worldwide have found that reduced sleep duration is associated with increased risks of obesity, morbidity, and mortality. It is well established that sleep loss causes fatigue and sleepiness, as well as errors and accidents that are due to its adverse neurobehavioral effects on alertness, mood, and cognitive functions. However, there are substantial, trait-like differences among people in the extent to which they experience such neurobehavioral deficits when sleep deprived. Common genetic variations involved in sleep-wake, circadian, and cognitive regulation may underlie these large inter-individual differences in neurobehavioral vulnerability to sleep deprivation, though it remains unclear whether different types of sleep deprivation involve the same phenotypic responses and same genotypic contributors. This project will be the first large-scale investigation of markers of differential cognitive vulnerability to both acute total sleep loss and chronic partial sleep loss. It will identify individuals who are at significant risk for fatigue and severe impairments from sleep loss. A total of 110 healthy adults will undergo a 13-day laboratory protocol to thoroughly characterize their cognitive, psychological and physiological responses to two of the most common forms of sleep loss--acute total sleep deprivation (1 night of sleep loss) and chronic partial sleep deprivation (5 nights of sleep limited to 4 hr). The findings from this study will represent a critical first step toward tailoring appropriate follow-up interventions for sleep loss and its symptomatic relief by finding predictors of at-risk individuals who should avoid sleep loss whenever possible, and/or seek effective countermeasures. Whether or not markers of neurobehavioral vulnerability to sleep loss are identified, the results of the project will help inform public policies pertaining to the need for adequate sleep and for countermeasures for sleep loss, and also will further our understanding and management of vulnerability to excessive sleepiness due to common sleep and medical disorders.

Study Overview

• Status: Completed
• Conditions: Sleep Restriction Then Total Sleep Deprivation; Total Sleep Deprivation Then Sleep Restriction
• Intervention / Treatment: Behavioral: Sleep

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Unit for Experimental Psychiatry, Sleep and Chronobiology Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A total of N=110 adult subjects (aged 21-50 yr), N=55 females and N=55 males of all ethnicities, will be randomized to the 2 different experimental conditions. Subjects must also be comparable in terms of their homeostatic and circadian sleep-wake regulation parameters. In order to be eligible to participate, subjects must meet the following inclusion criteria:

  1. Age between 21 and 50 years (average age of our current protocols is 31 years)
  2. Body mass index (BMI) within 20.5% of normal
  3. Stable, normally-timed sleep-wake cycle as determined by interview, 2-week daily sleep log, and 2-week wrist actigraphic evidence, and defined by:
  4. Habitual nocturnal sleep duration between 6.5h and 8.5h
  5. Habitual morning awakening between 0600h and 0930h

Exclusion Criteria:

• 1. No evidence of habitual napping 2. No shift work, transmeridian travel or irregular sleep/wake routine in the past 60 days 3. No sleep disorder, determined by history, actigraph, pulse oximetry and PSG 4. No history of mania or psychosis 5. No current depression as determined by the Beck Depression Inventory 6. No alcohol or drug abuse in the past year based upon history and urine toxicology screen

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PSD then TSD; baseline sleep, five nights sleep restriction, four nights recovery sleep, one night total sleep deprivation, one night recovery sleep	Behavioral: Sleep
Experimental: TSD then PSD; baseline sleep, one night total sleep deprivation, four nights recovery sleep, five nights sleep restriction, one night recovery sleep	Behavioral: Sleep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychomotor Vigilance Test	3, 10, or 20 minute simple, high-signal-load reaction time (RT)-based test invented by our group and designed to evaluate the ability to sustain attention and respond in a timely manner to salient signals	Completed every two hours during waking hours during each day of the study (14 days total) which includes days following baseline sleep, sleep restriction or sleep deprivation and recovery sleep

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Namni Goel, PhD, University of Pennsylvania

Publications and helpful links

General Publications

• Spaeth AM, Dinges DF, Goel N. Objective Measurements of Energy Balance Are Associated With Sleep Architecture in Healthy Adults. Sleep. 2017 Jan 1;40(1):zsw018. doi: 10.1093/sleep/zsw018.
• Spaeth AM, Dinges DF, Goel N. Sex and race differences in caloric intake during sleep restriction in healthy adults. Am J Clin Nutr. 2014 Aug;100(2):559-66. doi: 10.3945/ajcn.114.086579. Epub 2014 Jun 25.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: May 1, 2014
• First Posted (Estimate): May 5, 2014

Study Record Updates

• Last Update Posted (Estimate): December 2, 2015
• Last Update Submitted That Met QC Criteria: December 1, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Sleep Deprivation
• Other Study ID Numbers: 812523

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No