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

NCT02136420 | Completed Phase 4 Results

• 1 other identifier: 497997
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Vestibular

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (10)

Tilt perception, Training, placebo

EXPERIMENTAL

placebo

Behavioral: Hyper gravity training; Drug: Placebo

Tilt perception, No training, placebo

PLACEBO COMPARATOR

subject does test with no hypergravity training and placebo drug only

Drug: Placebo; Behavioral: No hypergravity training

Tilt perception, Training, promethazine

EXPERIMENTAL

promethazine 25 mg, one time 120 minutes prior to experiment

Drug: Promethazine; Behavioral: Hyper gravity training

Tilt perception,No training,promethazine

EXPERIMENTAL

promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training

Drug: Promethazine; Behavioral: No hypergravity training

Manual Control, Training, placebo

EXPERIMENTAL

placebo

Behavioral: Hyper gravity training; Drug: Placebo

Manual Control, No training, placebo

PLACEBO COMPARATOR

subject does test with no hyper gravity training and placebo drug only

Drug: Placebo; Behavioral: No hypergravity training

Manual Control, Training, promethazine

EXPERIMENTAL

promethazine 25 mg, one time 120 minutes prior to experiment

Drug: Promethazine; Behavioral: Hyper gravity training

Manual Control,No training,promethazine

EXPERIMENTAL

promethazine 25 mg, one time 120 minutes prior to experiment

Drug: Promethazine; Behavioral: No hypergravity training

Perceptual thresholds,drug then placebo

EXPERIMENTAL

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; Drug: Placebo

Perceptual thresholds,placebo then drug

EXPERIMENTAL

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; Drug: Placebo

Interventions

Promethazine DRUG

Subject receives promethazine

Also known as: Phenergan

Manual Control, Training, promethazine; Manual Control,No training,promethazine; Perceptual thresholds,drug then placebo; Perceptual thresholds,placebo then drug; Tilt perception, Training, promethazine; Tilt perception,No training,promethazine

Hyper gravity training BEHAVIORAL

Subject receives hypergravity training before testing

Manual Control, Training, placebo; Manual Control, Training, promethazine; Tilt perception, Training, placebo; Tilt perception, Training, promethazine

Placebo DRUG

Placebo

Also known as: corn starch

Manual Control, No training, placebo; Manual Control, Training, placebo; Perceptual thresholds,drug then placebo; Perceptual thresholds,placebo then drug; Tilt perception, No training, placebo; Tilt perception, Training, placebo

No hypergravity training BEHAVIORAL

Subjects do not receive normal Earth gravity

Manual Control, No training, placebo; Manual Control,No training,promethazine; Tilt perception, No training, placebo; Tilt perception,No training,promethazine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be in general good health

You may not qualify if:

• 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

Sponsors & Collaborators

• Faisal_Karmali@MEEI.HARVARD.EDU: lead
• National Space Biomedical Research Institute: collaborator
• Massachusetts Institute of Technology: collaborator

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 28439720 RESULT

MeSH Terms

Interventions

Promethazine; Starch

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Results Point of Contact

• Title: Faisal Karmali
• Organization: Massachusetts Eye and Ear Infirmary

faisal_karmali@meei.harvard.edu

617-573-5593

Study Officials

• Faisal Karmali, Ph.D.

  Massachusetts Eye and Ear Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double masking applies to arms 9\&10. Other arms use participant masking only.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Primary Investigator

Model Details: 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.

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 13, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 8, 2018
• Results First Posted: January 8, 2018

Record last verified: 2017-12

Locations

US (1)