Countermeasures to Reduce Sensorimotor Impairment and Space Motion Sickness Resulting From Altered Gravity Levels

Study Overview
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Brief Summary
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The investigators will study adaptation of motion perception and manual control in altered gravity, including the effects of a drug (promethazine). The investigators will also study whether promethazine affects motion perceptual thresholds.

Detailed Description
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Adaptation to altered gravity has been of concern from the earliest reports of space motion sickness, through the Apollo exploration era, and into current planning of exploration missions. The proposed research program takes a new approach which could lead to an effective, practical and acceptable protocol for preadapting astronauts to space flight. By using the gravito-inertial alterations possible with centrifugation in different body orientations the investigators will quantify an individual's sensory adaptation capability and use it to predict and to minimize the consequences of movement in any other gravity environment - eventually including weightlessness. The investigators will also study whether a drug (promethazine) affects motion perception and motion sickness.

Official Title
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Countermeasures to Reduce Sensorimotor Impairment and Space Motion Sickness Resulting From Altered Gravity Levels

Conditions
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Vestibular

Intervention / Treatment
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* Drug: Promethazine
* Behavioral: Hyper gravity training
* Drug: Placebo
* Behavioral: No hypergravity training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be in general good health Exclusion Criteria: Anyone who is not generally in good general health does not qualify Cardiovascular disease Severe diabetes Respiratory condition (e.g. asthma or emphysema) Narrow angle glaucoma Prostatic hypertrophy Gastrointestinal disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The design includes three separate studies: Arm 9&10 follows a crossover design. These results were reported in Diaz-Artiles et al 2017. Arms 1-4 are a separate study which follow a factorial design, with arm 2 serving as the placebo, arms 1 and 3 assessing the effects of two separate interventions and arm 4 assessing the effect of two combined interventions. Arms 5-8 are a separate study which follow a factorial design, with arm 6 serving as the placebo, arms 5 and 7 assessing the effects of two separate interventions and arm 8 assessing the effect of two combined interventions.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tilt perception, Training, placebo<br>placebo | Behavioral: Hyper gravity training<br>* Subject receives hypergravity training before testing<br>Drug: Placebo<br>* Placebo<br>* Other names: corn starch;|
| Placebo Comparator: Tilt perception, No training, placebo<br>subject does test with no hypergravity training and placebo drug only | Drug: Placebo<br>* Placebo<br>* Other names: corn starch;Behavioral: No hypergravity training<br>* Subjects do not receive normal Earth gravity<br>|
| Experimental: Tilt perception, Training, promethazine<br>promethazine 25 mg, one time 120 minutes prior to experiment | Drug: Promethazine<br>* Subject receives promethazine<br>* Other names: Phenergan;Behavioral: Hyper gravity training<br>* Subject receives hypergravity training before testing<br>|
| Experimental: Tilt perception,No training,promethazine<br>promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training | Drug: Promethazine<br>* Subject receives promethazine<br>* Other names: Phenergan;Behavioral: No hypergravity training<br>* Subjects do not receive normal Earth gravity<br>|
| Experimental: Manual Control, Training, placebo<br>placebo | Behavioral: Hyper gravity training<br>* Subject receives hypergravity training before testing<br>Drug: Placebo<br>* Placebo<br>* Other names: corn starch;|
| Placebo Comparator: Manual Control, No training, placebo<br>subject does test with no hyper gravity training and placebo drug only | Drug: Placebo<br>* Placebo<br>* Other names: corn starch;Behavioral: No hypergravity training<br>* Subjects do not receive normal Earth gravity<br>|
| Experimental: Manual Control, Training, promethazine<br>promethazine 25 mg, one time 120 minutes prior to experiment | Drug: Promethazine<br>* Subject receives promethazine<br>* Other names: Phenergan;Behavioral: Hyper gravity training<br>* Subject receives hypergravity training before testing<br>|
| Experimental: Manual Control,No training,promethazine<br>promethazine 25 mg, one time 120 minutes prior to experiment | Drug: Promethazine<br>* Subject receives promethazine<br>* Other names: Phenergan;Behavioral: No hypergravity training<br>* Subjects do not receive normal Earth gravity<br>|
| Experimental: Perceptual thresholds,drug then placebo<br>Subjects undergo perceptual motion threshold tests to determine the smallest motion they can reliably sense for yaw rotation, interaural translation and roll tilt. Each subject is tested twice, once with promethazine then once with placebo, separated by >4 days. This arm corresponds to results published in Diaz-Artiles et al 2017. | Drug: Promethazine<br>* Subject receives promethazine<br>* Other names: Phenergan;Drug: Placebo<br>* Placebo<br>* Other names: corn starch;|
| Experimental: Perceptual thresholds,placebo then drug<br>Subjects undergo perceptual motion threshold tests to determine the smallest motion they can reliably sense for yaw rotation, interaural translation and roll tilt. Each subject is tested twice, once with placebo then once with promethazine, separated by >4 days. This arm corresponds to results published in Diaz-Artiles et al 2017. | Drug: Promethazine<br>* Subject receives promethazine<br>* Other names: Phenergan;Drug: Placebo<br>* Placebo<br>* Other names: corn starch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Roll Tilt Perception After Exposure to Hypogravity | Note that this applies to arms 1-4 only. Subjects sat on a chair on a moving platform on top of a centrifuge that created an artificial gravity environment. Subjects were repeatedly roll tilted to angles between 11 and 19 degrees, and then reported their perceived tilt angle using a subjective visual vertical task. They did this while experiencing centripetal acceleration equivalent to Earth gravity (1 Gz), and then hypogravity (0.5 Gz). We hypothesized that, after entering hypogravity, subjects would tend to underestimate their tilt angle. We calculated the percent change in their perception of tilt between 1 Gz and 0.5 Gz. | 1 session | 
| Yaw Perceptual Motion Threshold | This is a perceptual self-motion threshold that measures the precision of the vestibular system. It is analogous to an audiogram, but for motion. Subjects sat on a motorized platform which repeatedly provided them with small motions to the left or right. After each motion subjects report whether they perceived a motion to the left or right. Based on subject responses, a psychometric curve fit is performed that determines the threshold (the standard deviation of the underlying cumulative Gaussian). Yaw rotation means rotations about an axis that is perpendicular to gravity. This outcome measure applies only to arm 5 subjects. | 2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication | 
| Roll Perceptual Motion Threshold | This is a perceptual self-motion threshold that measures the precision of the vestibular system. It is analogous to an audiogram, but for motion. Subjects sat on a motorized platform which repeatedly provided them with small motions to the left or right. After each motion subjects report whether they perceived a motion to the left or right. Based on subject responses, a psychometric curve fit is performed that determines the threshold (the standard deviation of the underlying cumulative Gaussian). Roll tilt means rotations about an axis that is Earth-horizontal. This outcome measure applies only to arm 5 subjects. | 2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication | 
| Interaural Perceptual Motion Threshold | This is a perceptual self-motion threshold that measures the precision of the vestibular system. It is analogous to an audiogram, but for motion. Subjects sat on a motorized platform which repeatedly provided them with small motions to the left or right. After each motion subjects report whether they perceived a motion to the left or right. Based on subject responses, a psychometric curve fit is performed that determines the threshold (the standard deviation of the underlying cumulative Gaussian). Interaural translation refers to translations in the horizontal plane to the subject's left or right. This outcome measure applies only to arm 5 subjects. | 2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication | 
| Percent Change in Manual Control Performance After Exposure to Hypogravity | Note that this applies to arms 6-9 only. Subjects sat on a chair on a moving platform on top of a centrifuge that created an artificial gravity environment. Subjects completed a manual control task in which their charge was randomly perturbed in roll tilt, and they used a joystick to attempt to keep themselves aligned with upright, while in the dark. They did this while experiencing centripetal acceleration equivalent to Earth gravity (1 Gz), and then hypogravity (0.5 Gz). We calculated their performance by calculating the standard deviation of chair position across time, with a smaller number indicating better performance. Then we calculated the percent change in their performance between 1 Gz and 0.5 Gz. | 1 session |