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

• ClinicalTrials.gov Identifier: NCT02136420
• Recruitment Status: Completed
• First Posted: May 13, 2014
• Results First Posted: January 8, 2018
• Last Update Posted: January 8, 2018
• Sponsor: Faisal_Karmali@MEEI.HARVARD.EDU
• Collaborators: National Space Biomedical Research Institute; Massachusetts Institute of Technology
• Information provided by (Responsible Party): Faisal_Karmali@MEEI.HARVARD.EDU, Massachusetts Eye and Ear Infirmary

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vestibular	Drug: Promethazine; Behavioral: Hyper gravity training; Drug: Placebo; Behavioral: No hypergravity training	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment

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.

• Masking: Double (Participant, Investigator)
• Masking Description: Double masking applies to arms 9&10. Other arms use participant masking only.
• Primary Purpose: Basic Science
• Official Title: Countermeasures to Reduce Sensorimotor Impairment and Space Motion Sickness Resulting From Altered Gravity Levels
• Study Start Date: June 2014
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tilt perception, Training, placebo; placebo	Behavioral: Hyper gravity training; Subject receives hypergravity training before testing; Drug: Placebo; Placebo; Other Name: corn starch
Placebo Comparator: Tilt perception, No training, placebo; subject does test with no hypergravity training and placebo drug only	Drug: Placebo; Placebo; Other Name: corn starch; Behavioral: No hypergravity training; Subjects do not receive normal Earth gravity
Experimental: Tilt perception, Training, promethazine; promethazine 25 mg, one time 120 minutes prior to experiment	Drug: Promethazine; Subject receives promethazine; Other Name: Phenergan; Behavioral: Hyper gravity training; Subject receives hypergravity training before testing
Experimental: Tilt perception,No training,promethazine; promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training	Drug: Promethazine; Subject receives promethazine; Other Name: Phenergan; Behavioral: No hypergravity training; Subjects do not receive normal Earth gravity
Experimental: Manual Control, Training, placebo; placebo	Behavioral: Hyper gravity training; Subject receives hypergravity training before testing; Drug: Placebo; Placebo; Other Name: corn starch
Placebo Comparator: Manual Control, No training, placebo; subject does test with no hyper gravity training and placebo drug only	Drug: Placebo; Placebo; Other Name: corn starch; Behavioral: No hypergravity training; Subjects do not receive normal Earth gravity
Experimental: Manual Control, Training, promethazine; promethazine 25 mg, one time 120 minutes prior to experiment	Drug: Promethazine; Subject receives promethazine; Other Name: Phenergan; Behavioral: Hyper gravity training; Subject receives hypergravity training before testing
Experimental: Manual Control,No training,promethazine; promethazine 25 mg, one time 120 minutes prior to experiment	Drug: Promethazine; Subject receives promethazine; Other Name: Phenergan; Behavioral: No hypergravity training; Subjects do not receive normal Earth gravity
Experimental: 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. This arm corresponds to results published in Diaz-Artiles et al 2017.	Drug: Promethazine; Subject receives promethazine; Other Name: Phenergan; Drug: Placebo; Placebo; Other Name: corn starch
Experimental: 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. This arm corresponds to results published in Diaz-Artiles et al 2017.	Drug: Promethazine; Subject receives promethazine; Other Name: Phenergan; Drug: Placebo; Placebo; Other Name: corn starch

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Roll Tilt Perception After Exposure to Hypogravity [ Time Frame: 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.

2. Yaw Perceptual Motion Threshold [ Time Frame: 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.

3. Roll Perceptual Motion Threshold [ Time Frame: 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.

4. Interaural Perceptual Motion Threshold [ Time Frame: 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.

5. Percent Change in Manual Control Performance After Exposure to Hypogravity [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Faisal_Karmali@MEEI.HARVARD.EDU

National Space Biomedical Research Institute

Massachusetts Institute of Technology

Investigators

• Principal Investigator: Faisal Karmali, Ph.D.; Massachusetts Eye and Ear Infirmary

More Information

Publications of Results:

Diaz-Artiles A, Priesol AJ, Clark TK, Sherwood DP, Oman CM, Young LR, Karmali F. The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds. J Assoc Res Otolaryngol. 2017 Aug;18(4):581-590. doi: 10.1007/s10162-017-0622-z. Epub 2017 Apr 24.

• Responsible Party: Faisal_Karmali@MEEI.HARVARD.EDU, Primary Investigator, Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT02136420
• Other Study ID Numbers: 497997
• First Posted: May 13, 2014
• Results First Posted: January 8, 2018
• Last Update Posted: January 8, 2018
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Motion Sickness; Space Motion Sickness; Promethazine; Diphenhydramine; Antipruritics; Dermatologic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Hypnotics and Sedatives; Central Nervous System Depressants; Anesthetics, Local; Anesthetics; Sensory System Agents; Peripheral Nervous System Agents; Antiemetics; Autonomic Agents; Gastrointestinal Agents