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

• Sponsor: [e-mail] (Other)
• Overall Status: Completed
• CT.gov ID: NCT02136420
• Collaborator: National Space Biomedical Research Institute (Other), Massachusetts Institute of Technology (Other)
• Enrollment: 30
• Location: 1
• Arms: 10
• Duration (Months): 30
• Patients Per Site Per Month: 1

Study Details

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
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: The design includes three separate studies: Arm 9&10 follows a crossover design. These results were reported in Diaz-Artiles et al 2017. 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. 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.The design includes three separate studies:Arm 9&10 follows a crossover design. These results were reported in Diaz-Artiles et al 2017. 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. 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: Jun 1, 2014
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 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 Names: corn starch
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	Drug: Promethazine; Subject receives promethazine; Other Names: 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 Names: 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 Names: 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 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	Drug: Promethazine; Subject receives promethazine; Other Names: 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 Names: 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 Names: Phenergan ; Drug: Placebo; Placebo; Other Names: 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 Names: Phenergan ; Drug: Placebo; Placebo; Other Names: corn starch

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• [e-mail]
• National Space Biomedical Research Institute
• Massachusetts Institute of Technology

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: [e-mail], Primary Investigator, Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT02136420
• Other Study ID Numbers: 497997
• First Posted: May 13, 2014
• Last Update Posted: Jan 8, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Motion Sickness; Space Motion Sickness; Promethazine; Diphenhydramine

Study Results

Participant Flow

Arm/Group Title	Tilt Perception, Training, Placebo	Tilt Perception, No Training, Placebo	Tilt Perception, Training, Promethazine	Tilt Perception,No Training,Promethazine	Manual Control, Training, Placebo	Manual Control, No Training, Placebo	Manual Control, Training, Promethazine	Manual Control,No Training,Promethazine	Perceptual Thresholds,Drug Then Placebo	Perceptual Thresholds,Placebo Then Drug
Arm/Group Description	placebo	subject does test with no hypergravity training and placebo drug only	promethazine 25 mg, one time 120 minutes prior to experiment	promethazine 25 mg, one time 120 minutes prior to experiment. No hypergravity training	placebo	subject does test with no hyper gravity training and placebo drug only	promethazine 25 mg, one time 120 minutes prior to experiment	promethazine 25 mg, one time 120 minutes prior to experiment	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.	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.
Period Title: Overall Study
STARTED	10	0	0	0	10	0	0	0	5	5
COMPLETED	9	0	0	0	10	0	0	0	5	5
NOT COMPLETED	1	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Tilt Perception, Training, Placebo	Manual Control, Training, Placebo	Perceptual Thresholds,Drug Then Placebo	Perceptual Thresholds,Placebo Then Drug	Total
Arm/Group Description	placebo Hyper gravity training: Subject receives hypergravity training before testing Placebo: Placebo	placebo Hyper gravity training: Subject receives hypergravity training before testing Placebo: 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	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	Total of all reporting groups
Overall Participants	10	10	5	5	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.3 (6.4)	28.0 (6.3)	27.4 (4.2)	24.8 (2.9)	27.6 (4.3)
Sex: Female, Male (Count of Participants)
Female	4 40%	6 60%	1 20%	2 40%	13 43.3%
Male	6 60%	4 40%	4 80%	3 60%	17 56.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	1 10%	1 20%	1 20%	4 13.3%
Not Hispanic or Latino	9 90%	9 90%	4 80%	4 80%	26 86.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 30%	3 30%	0 0%	0 0%	6 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 10%	0 0%	1 20%	0 0%	2 6.7%
White	6 60%	7 70%	4 80%	3 60%	20 66.7%
More than one race	0 0%	0 0%	0 0%	2 40%	2 6.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Roll Tilt Perception After Exposure to Hypogravity
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Training, Placebo
Arm/Group Description	placebo Hyper gravity training: Subject receives hypergravity training before testing Placebo: Placebo
Measure Participants	9
Mean (Full Range) [percentage change]	27.0

2. Primary Outcome

Title	Yaw Perceptual Motion Threshold
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Perceptual Thresholds,Drug Then Placebo	Perceptual Thresholds,Placebo Then Drug
Arm/Group Description	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	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.
Measure Participants	5	5
Placebo	.83 (.25)	.92 (.29)
Promethazine	.86 (.19)	1.06 (.26)

3. Primary Outcome

Title	Roll Perceptual Motion Threshold
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Perceptual Thresholds,Drug Then Placebo	Perceptual Thresholds,Placebo Then Drug
Arm/Group Description	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	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.
Measure Participants	5	5
Placebo	.27 (.15)	.32 (.12)
Promethazine	.39 (.20)	.39 (.13)

4. Primary Outcome

Title	Interaural Perceptual Motion Threshold
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Perceptual Thresholds,Drug Then Placebo	Perceptual Thresholds,Placebo Then Drug
Arm/Group Description	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	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.
Measure Participants	5	5
Placebo	.57 (.17)	.78 (.23)
Promethazine	.77 (.39)	.80 (.16)

5. Primary Outcome

Title	Percent Change in Manual Control Performance After Exposure to Hypogravity
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Training, Placebo
Arm/Group Description	placebo Hyper gravity training: Subject receives hypergravity training before testing Placebo: Placebo
Measure Participants	10
Mean (Standard Deviation) [percentage change]	75.4 (48.8)

Adverse Events

Time Frame	1 week
Arm/Group Title	Tilt Perception, Training, Placebo		Tilt Perception, No Training, Placebo		Tilt Perception, Training, Promethazine		Tilt Perception, No Training, Promethazine		Perceptual Threshold Testing: Promethazine		Perceptual Motion Threshold Testing: Placebo		Manual Control, Training, Placebo		Manual Control, No Training, Placebo		Manual Control, Training, Promethazine		Manual Control, No Training, Promethazine
Arm/Group Description
All Cause Mortality
	Tilt Perception, Training, Placebo		Tilt Perception, No Training, Placebo		Tilt Perception, Training, Promethazine		Tilt Perception, No Training, Promethazine		Perceptual Threshold Testing: Promethazine		Perceptual Motion Threshold Testing: Placebo		Manual Control, Training, Placebo		Manual Control, No Training, Placebo		Manual Control, Training, Promethazine		Manual Control, No Training, Promethazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Tilt Perception, Training, Placebo		Tilt Perception, No Training, Placebo		Tilt Perception, Training, Promethazine		Tilt Perception, No Training, Promethazine		Perceptual Threshold Testing: Promethazine		Perceptual Motion Threshold Testing: Placebo		Manual Control, Training, Placebo		Manual Control, No Training, Placebo		Manual Control, Training, Promethazine		Manual Control, No Training, Promethazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/0 (NaN)		0/00 (NaN)		0/0 (NaN)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Tilt Perception, Training, Placebo		Tilt Perception, No Training, Placebo		Tilt Perception, Training, Promethazine		Tilt Perception, No Training, Promethazine		Perceptual Threshold Testing: Promethazine		Perceptual Motion Threshold Testing: Placebo		Manual Control, Training, Placebo		Manual Control, No Training, Placebo		Manual Control, Training, Promethazine		Manual Control, No Training, Promethazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.