VestibularPhase 4NCT02136420
Countermeasures to Reduce Sensorimotor Impairment and Space Motion Sickness Resulting From Altered Gravity Levels
A Phase 4 study testing Promethazine, Hyper gravity training and No hypergravity training in people with Vestibular, run by Faisal_Karmali@MEEI.HARVARD.EDU at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Vestibular
- What is being tested?
- Promethazine, Hyper gravity training and No hypergravity training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Dec 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be in general good health
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
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.
Read the 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.
- Conditions
- Vestibular
- Being tested
- Promethazine, Hyper gravity training, Placebo, No hypergravity training
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PromethazineDrug
Also called Phenergan
Subject receives promethazine
Hyper gravity trainingBehavioural
Subject receives hypergravity training before testing
PlaceboDrug
Also called corn starch
Placebo
No hypergravity trainingBehavioural
Subjects do not receive normal Earth gravity
| Study group | Role | What they receive |
|---|---|---|
| Tilt perception, Training, placebo | Experimental | placebo Receives: Behavioral: Hyper gravity training; Drug: Placebo |
| Tilt perception, No training, placebo | Placebo comparator | subject does test with no hypergravity training and placebo drug only Receives: Drug: Placebo; Behavioral: No hypergravity training |
| Tilt perception, Training, promethazine | Experimental | promethazine 25 mg, one time 120 minutes prior to experiment Receives: 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 Receives: Drug: Promethazine; Behavioral: No hypergravity training |
| Manual Control, Training, placebo | Experimental | placebo Receives: 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 Receives: Drug: Placebo; Behavioral: No hypergravity training |
| Manual Control, Training, promethazine | Experimental | promethazine 25 mg, one time 120 minutes prior to experiment Receives: Drug: Promethazine; Behavioral: Hyper gravity training |
| Manual Control,No training,promethazine | Experimental | promethazine 25 mg, one time 120 minutes prior to experiment Receives: 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. Receives: 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. Receives: Drug: Promethazine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 1 session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2014 (estimated)
- Study startJun 2014
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VestibularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Faisal_Karmali@MEEI.HARVARD.EDU
- Sponsor type
- University, hospital or other
- Collaborators
- National Space Biomedical Research Institute, Massachusetts Institute of Technology
- Responsible party
- Sponsor-investigator, Faisal_Karmali@MEEI.HARVARD.EDU, Massachusetts Eye and Ear Infirmary
- Investigators
- Faisal Karmali, Ph.D., Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02136420
- Sponsor's protocol ID
- 497997
- Status last verified
- Dec 2017
- First submitted
- 30 Apr 2014
- Last updated
- 8 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
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.
PubMed 28439720
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Countermeasures to Reduce Sensorimotor Impairment and Space Motion Sickness Resulting From Altered Gravity Levels
- ClinicalTrials.gov ID
- NCT02136420
- Acronym / sponsor ID
- 497997
- Conditions
- Vestibular
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Faisal_Karmali@MEEI.HARVARD.EDUUniversity, hospital or other
- Collaborators
- National Space Biomedical Research Institute, Massachusetts Institute of Technology
- Study start
- Jun 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 13 May 2014 (estimated)
- Results
- Posted 8 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 10
- 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.
| Arm | Type | Receives |
|---|---|---|
| Tilt perception, Training, placebo | Experimental | Behavioral: Hyper gravity training, Drug: Placeboplacebo |
| Tilt perception, No training, placebo | Placebo comparator | Drug: Placebo, Behavioral: No hypergravity trainingsubject does test with no hypergravity training and placebo drug only |
| Tilt perception, Training, promethazine | Experimental | Drug: Promethazine, Behavioral: Hyper gravity trainingpromethazine 25 mg, one time 120 minutes prior to experiment |
| Tilt perception,No training,promethazine | Experimental | Drug: Promethazine, Behavioral: No hypergravity trainingpromethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training |
| Manual Control, Training, placebo | Experimental | Behavioral: Hyper gravity training, Drug: Placeboplacebo |
| Manual Control, No training, placebo | Placebo comparator | Drug: Placebo, Behavioral: No hypergravity trainingsubject does test with no hyper gravity training and placebo drug only |
| Manual Control, Training, promethazine | Experimental | Drug: Promethazine, Behavioral: Hyper gravity trainingpromethazine 25 mg, one time 120 minutes prior to experiment |
| Manual Control,No training,promethazine | Experimental | Drug: Promethazine, Behavioral: No hypergravity trainingpromethazine 25 mg, one time 120 minutes prior to experiment |
| Perceptual thresholds,drug then placebo | Experimental | Drug: Promethazine, Drug: PlaceboSubjects 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 | Experimental | Drug: Promethazine, Drug: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Subjects must be in general good health
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PromethazineAlso: PhenerganSubject receives promethazine | Drug | 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 trainingSubject receives hypergravity training before testing | Behavioural | Manual Control, Training, placebo, Manual Control, Training, promethazine, Tilt perception, Training, placebo, Tilt perception, Training, promethazine |
| PlaceboAlso: corn starchPlacebo | Drug | 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 trainingSubjects do not receive normal Earth gravity | Behavioural | Manual Control, No training, placebo, Manual Control,No training,promethazine, Tilt perception, No training, placebo, Tilt perception,No training,promethazine |
Primary outcome
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28439720Diaz-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Faisal Karmali, Ph.D. principal investigator
Massachusetts Eye and Ear Infirmary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Promethazine, Hyper gravity training and No hypergravity training in people with Vestibular, run by Faisal_Karmali@MEEI.HARVARD.EDU at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Roll Tilt Perception After Exposure to Hypogravity (time frame: 1 session). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02136420, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2018.