Vestibular
Conditions
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.
Interventions
DRUGPromethazine
Subject receives promethazine
BEHAVIORALHyper gravity training
Subject receives hypergravity training before testing
DRUGPlacebo
Placebo
BEHAVIORALNo hypergravity training
Subjects do not receive normal Earth gravity
Sponsors
National Space Biomedical Research Institute
Massachusetts Institute of Technology
Faisal_Karmali@MEEI.HARVARD.EDU
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double masking applies to arms 9&10. Other arms use participant masking only.
Intervention model description
The design includes three separate studies: 1. Arm 9&10 follows a crossover design. These results were reported in Diaz-Artiles et al 2017. 2. 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. 3. 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tilt Perception, Training, Placebo placebo
Hyper gravity training: Subject receives hypergravity training before testing
Placebo: Placebo | 10 |
| Manual Control, Training, Placebo placebo
Hyper gravity training: Subject receives hypergravity training before testing
Placebo: Placebo | 10 |
| Perceptual Thresholds,Drug Then 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.
Promethazine: Subject receives promethazine
Placebo: Placebo | 5 |
| Perceptual Thresholds,Placebo Then Drug 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.
Promethazine: Subject receives promethazine
Placebo: Placebo | 5 |
| Total | 30 |
Baseline characteristics
| Characteristic | Tilt Perception, Training, Placebo | Manual Control, Training, Placebo | Perceptual Thresholds,Drug Then Placebo | Perceptual Thresholds,Placebo Then Drug | Total |
|---|---|---|---|---|---|
| Age, Continuous | 28.3 years STANDARD_DEVIATION 6.4 | 28.0 years STANDARD_DEVIATION 6.3 | 27.4 years STANDARD_DEVIATION 4.2 | 24.8 years STANDARD_DEVIATION 2.9 | 27.6 years STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 4 Participants | 4 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 4 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 1 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 4 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 10 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 10 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Training, Placebo | Interaural Perceptual Motion Threshold | Placebo | .57 cm per sec | Standard Deviation 0.17 |
| Training, Placebo | Interaural Perceptual Motion Threshold | Promethazine | .77 cm per sec | Standard Deviation 0.39 |
| Perceptual Thresholds,Placebo Then Drug | Interaural Perceptual Motion Threshold | Placebo | .78 cm per sec | Standard Deviation 0.23 |
| Perceptual Thresholds,Placebo Then Drug | Interaural Perceptual Motion Threshold | Promethazine | .80 cm per sec | Standard Deviation 0.16 |
Primary
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.
Time frame: 1 session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Training, Placebo | Percent Change in Manual Control Performance After Exposure to Hypogravity | 75.4 percentage change | Standard Deviation 48.8 |
Primary
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.
Time frame: 1 session
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Training, Placebo | Percent Change in Roll Tilt Perception After Exposure to Hypogravity | 27.0 percentage change |
Primary
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.
Time frame: 2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Training, Placebo | Roll Perceptual Motion Threshold | Placebo | .27 deg per sec | Standard Deviation 0.15 |
| Training, Placebo | Roll Perceptual Motion Threshold | Promethazine | .39 deg per sec | Standard Deviation 0.2 |
| Perceptual Thresholds,Placebo Then Drug | Roll Perceptual Motion Threshold | Placebo | .32 deg per sec | Standard Deviation 0.12 |
| Perceptual Thresholds,Placebo Then Drug | Roll Perceptual Motion Threshold | Promethazine | .39 deg per sec | Standard Deviation 0.13 |
Primary
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.
Time frame: 2 sessions separated by at least four days; measurements made 2 hrs after ingestion of medication
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Training, Placebo | Yaw Perceptual Motion Threshold | Placebo | .83 deg per sec | Standard Deviation 0.25 |
| Training, Placebo | Yaw Perceptual Motion Threshold | Promethazine | .86 deg per sec | Standard Deviation 0.19 |
| Perceptual Thresholds,Placebo Then Drug | Yaw Perceptual Motion Threshold | Placebo | .92 deg per sec | Standard Deviation 0.29 |
| Perceptual Thresholds,Placebo Then Drug | Yaw Perceptual Motion Threshold | Promethazine | 1.06 deg per sec | Standard Deviation 0.26 |