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

Phase 4

Completed

Conditions: Vestibular

Interventions: Drug: Promethazine
Behavioral: No hypergravity training
Behavioral: Hyper gravity training
Drug: Placebo

Registration Number: NCT02136420

Lead Sponsor: Faisal_Karmali@MEEI.HARVARD.EDU

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tilt perception,No training,promethazine	No hypergravity training	promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training
Tilt perception, No training, placebo	No hypergravity training	subject does test with no hypergravity training and placebo drug only
Tilt perception, Training, promethazine	Hyper gravity training	promethazine 25 mg, one time 120 minutes prior to experiment
Tilt perception, Training, placebo	Hyper gravity training	placebo
Tilt perception, Training, placebo	Placebo	placebo
Tilt perception, No training, placebo	Placebo	subject does test with no hypergravity training and placebo drug only
Manual Control, Training, placebo	Hyper gravity training	placebo
Manual Control, Training, placebo	Placebo	placebo
Manual Control, No training, placebo	Placebo	subject does test with no hyper gravity training and placebo drug only
Manual Control, No training, placebo	No hypergravity training	subject does test with no hyper gravity training and placebo drug only
Manual Control, Training, promethazine	Promethazine	promethazine 25 mg, one time 120 minutes prior to experiment
Manual Control, Training, promethazine	Hyper gravity training	promethazine 25 mg, one time 120 minutes prior to experiment
Manual Control,No training,promethazine	Promethazine	promethazine 25 mg, one time 120 minutes prior to experiment
Manual Control,No training,promethazine	No hypergravity training	promethazine 25 mg, one time 120 minutes prior to experiment
Perceptual thresholds,drug then placebo	Promethazine	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.
Perceptual thresholds,drug then placebo	Placebo	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.
Perceptual thresholds,placebo then drug	Placebo	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.
Tilt perception, Training, promethazine	Promethazine	promethazine 25 mg, one time 120 minutes prior to experiment
Tilt perception,No training,promethazine	Promethazine	promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training
Perceptual thresholds,placebo then drug	Promethazine	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.

Primary Outcome Measures

Name	Time	Method
Percent Change in Roll Tilt Perception After Exposure to Hypogravity	1 session	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.
Yaw Perceptual Motion Threshold	2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication	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.
Roll Perceptual Motion Threshold	2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication	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.
Interaural Perceptual Motion Threshold	2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication	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.
Percent Change in Manual Control Performance After Exposure to Hypogravity	1 session	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.