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

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.

Study Overview

• Status: Completed
• Conditions: Vestibular
• Intervention / Treatment: Drug: Placebo; Behavioral: Hyper gravity training; Behavioral: No hypergravity training; Drug: Promethazine

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tilt perception, Training, placebo; placebo	Drug: Placebo; Placebo; Other Names: corn starch; Behavioral: Hyper gravity training; Subject receives hypergravity training before testing
Placebo Comparator: Tilt perception, No training, placebo; subject does test with no hypergravity training and placebo drug only	Drug: Placebo; Placebo; Other Names: 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	Behavioral: Hyper gravity training; Subject receives hypergravity training before testing; Drug: Promethazine; Subject receives promethazine; Other Names: Phenergan
Experimental: Tilt perception,No training,promethazine; promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training	Behavioral: No hypergravity training; Subjects do not receive normal Earth gravity; Drug: Promethazine; Subject receives promethazine; Other Names: Phenergan
Experimental: Manual Control, Training, placebo; placebo	Drug: Placebo; Placebo; Other Names: corn starch; Behavioral: Hyper gravity training; Subject receives hypergravity training before testing
Placebo Comparator: Manual Control, No training, placebo; subject does test with no hyper gravity training and placebo drug only	Drug: Placebo; Placebo; Other Names: 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	Behavioral: Hyper gravity training; Subject receives hypergravity training before testing; Drug: Promethazine; Subject receives promethazine; Other Names: Phenergan
Experimental: Manual Control,No training,promethazine; promethazine 25 mg, one time 120 minutes prior to experiment	Behavioral: No hypergravity training; Subjects do not receive normal Earth gravity; Drug: Promethazine; Subject receives promethazine; Other Names: Phenergan
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: Placebo; Placebo; Other Names: corn starch; Drug: Promethazine; Subject receives promethazine; Other Names: Phenergan
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: Placebo; Placebo; Other Names: corn starch; Drug: Promethazine; Subject receives promethazine; Other Names: Phenergan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Faisal_Karmali@MEEI.HARVARD.EDU
• Collaborators: Massachusetts Institute of Technology; National Space Biomedical Research Institute
• Investigators: Principal Investigator: Faisal Karmali, Ph.D., Massachusetts Eye and Ear Infirmary

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: April 30, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Actual): January 8, 2018
• Last Update Submitted That Met QC Criteria: December 7, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Motion Sickness; Space Motion Sickness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Diphenhydramine; Promethazine
• Other Study ID Numbers: 497997

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided