This study aims to investigate the impairing effects of known central nervous system (CNS) stressors in a controlled environment in order to predict and mitigate analogous risks in spaceflight. Up to 56 healthy individuals aged 25-60 will spend approx. 110 hours in a laboratory, where they will be exposed to 27 hours of sleep deprivation and will consume alcohol to reach a BAC of 0.08 on a separate day. They will perform cognitive and sensorimotor tasks and undergo MRIs and blood draws.
This study aims to investigate the impairing effects of known central nervous system (CNS) stressors in a controlled environment in order to predict and mitigate analogous risks in spaceflight. Up to 56 healthy individuals aged 25-60 will spend six days and five nights (24 hours a day) in a laboratory, where they will be exposed to 27 hours of sleep deprivation and will consume alcohol to reach a BAC of 0.08 on a separate day. They will also have an adaptation night, a control condition with no daytime or nighttime interventions, and a recovery night following the sleep deprivation condition. All subjects in a group will receive the three conditions (sleep deprivation, alcohol administration and control) in the same order, but this order will vary between study runs. Subjects will perform cognitive tests and sensorimotor tasks throughout the waking periods. They will undergo one MRI and two blood draws for each of the three conditions, for a total of three MRIs and six blood draws per subject. The scans and blood draws are timed to occur near the highest predicted level of impairment in order to capture the dose-response relationship between the stressor and performance. Combined with research from parallel rodent studies performed at a partner institution where rodents are exposed to alcohol administration, sleep deprivation and radiation, these data may allow us to estimate the performance decrements associated with exposure to radiation in humans to assess the radiation risks of spaceflight.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
56
For the alcohol administration condition (ALC), subjects will consume alcohol within a window of approximately fifteen minutes in the morning in order to induce a blood alcohol content (BAC) level of 0.08%, in the form of 80-proof vodka mixed with fruit juice or clear, noncaffeinated soda at a 1:3 ratio. The specific dosage is determined by the Widmark formula, factoring in each individual's body weight and sex. BAC will be measured by a NHTSA-approved evidential breath testing (EBT) device, which measures breath alcohol content (BrAC, in grams per 210 liters of breath) and converts it to BAC (in g/100ml or g/dl). BAC will be measured before and after every task until subjects go to bed at 11 PM, at which point their BAC is expected to be at or close to 0.00%. Subjects will undergo an MRI (shortly after alcohol consumption at what is anticipated to be their highest level of intoxication to capture the impairing effects) and two blood draws (in the morning and afternoon).
For the sleep deprivation condition (SD1\&2), subjects will remain awake for 27 hours from 8 AM until 11 AM the following morning (SD1). They will perform testing at regular intervals throughout the day and overnight, and they have two blood draws during the extended wake period. Subjects will undergo an MRI after approximately 25 hours of wakefulness, followed by a three-hour nap opportunity from 11 AM until 2 PM. They will then remain awake from 2 PM until 11 PM for testing and meals before returning to the standard sleep period of 11 PM to 8 AM (SD2). Caffeine will not be available to subjects during this period nor will it be available at any other time during the study.
During the control condition (CTRL), subjects will have no stressor intervention. They will not consume alcohol and they will sleep during the standard period of 11 PM to 8 AM. They will perform testing at regular intervals throughout the day. They will undergo an MRI in the morning, and have two blood draws (in the morning and afternoon).
Psychomotor Vigilance Task (PVT) lapses
The number of lapses in the Psychomotor Vigilance Task (PVT) in the Cognition battery, a 3-minute task that records reaction times to visual stimuli and has been validated as a sensitive measure of vigilant attention. Subjects are instructed to monitor a blank box on the screen, and to hit the space bar once a millisecond counter appears in the box and starts incrementing. The box displays the reaction time for one second then resets, with random interstimulus intervals between 2-5 seconds. Lapses are defined as response times greater than or equal to 355 milliseconds. The results are reported as the number of lapses with a standard deviation for the impaired condition and the non-impaired control state. More lapses suggest greater impairment.
Time frame: From Study Day 2 through Study Day 6 (to include each of the three conditions: ALC, CTRL, SD1&2).
Cognition Test Battery Speed
A single variable representing response time across 10 Cognitive tasks that cover a range of cognitive domains with known cerebral representation. Subjects complete this approximately every three hours during wake. Test scores are adjusted for practice and stimulus set effects, and z-transformed based on average and standard deviation across all tests taken. Speed across cognitive domains is calculated by averaging z-scores across the 10 tests. Higher scores reflect faster speed. The final measure is reported as the least square means of the z-score. Scores between -0.2 and +0.2 suggest no effect on speed (0=population mean). More negative scores suggest larger negative effects (i.e. scores between -0.2 to -0.5 mean slightly slower; -0.5 to -0.8 moderately slower; scores beyond -0.8 significantly slower). Greater positive scores suggest larger positive effects (i.e. scores between +0.2 to +0.5 mean slightly faster; +0.5 to +0.8 moderately faster; above +0.8 significantly faster).
Time frame: From Study Day 2 through Study Day 6 (to include each of the three conditions: ALC, CTRL, SD1&2).
Cognition Test Battery Accuracy
A single variable representing accuracy across 10 Cognitive tasks that cover a range of cognitive domains with known cerebral representation. Test scores are adjusted for practice and stimulus set effects, and z-transformed based on average and standard deviation across all tests taken. Accuracy across cognitive domains is calculated by averaging z-scores across the 10 tests. Higher scores reflect better accuracy. The final measure is reported as the least square means of the z-score. Scores between -0.2 and +0.2 suggest no effect on accuracy (0=population mean). More negative scores suggest larger negative effects (i.e. scores between -0.2 to -0.5 mean slightly less accurate; -0.5 to -0.8 moderately less accurate; scores beyond -0.8 significantly less accurate). Greater positive scores suggest larger positive effects (i.e. scores between +0.2 to +0.5 mean slightly more accurate; +0.5 to +0.8 moderately more accurate; above +0.8 significantly more accurate).
Time frame: From Study Day 2 through Study Day 6 (to include each of the three conditions: ALC, CTRL, SD1&2).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.