BLINK: Bifocal Lenses In Nearsighted Kids

• Sponsor: Ohio State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02255474
• Collaborator: University of Houston (Other), National Eye Institute (NEI) (NIH)
• Enrollment: 294
• Locations: 2
• Arms: 3
• Actual Duration (Months): 57
• Patients Per Site: 147
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

This study will evaluate the use of two different bifocal contact lens add powers to prevent further nearsighted progression in children ages 7 to 11 years old. It is theorized that the profile of the bifocal lenses will decrease the amount of change in nearsightedness that the children experience.

Condition or Disease	Intervention/Treatment	Phase
Refractive Errors	Device: Biofinity Multifocal D +1.50 add; Device: Biofinity Multifocal D +2.50 add; Device: Biofinity	N/A

Detailed Description

The primary goal of this project is to determine whether a commercially available soft bifocal contact lens with a distance-center design can slow myopia progression in children. Using soft bifocal contact lenses to manipulate the peripheral optics of the eye is a novel use for a standard contact lens that may keep children from becoming as nearsighted as they would otherwise. Secondary goals are to determine whether the amount of myopic defocus imposed on the peripheral retina by soft bifocal contact lenses is associated in a dose-dependent manner with slowed myopic progression and to determine whether peripheral myopic blur acts to slow eye growth locally or globally. These important pieces of information will enable investigators to learn about the role of peripheral optics for regulating eye growth, which could ultimately lead to optimization of optical signals to slow myopia progression. Ultimately, the information could be used to design optical devices to prevent the onset of myopia in young children.

Slowing myopia progression or eventually preventing myopia onset could potentially affect approximately 60 million children in the United States alone. While the consequences of myopia are rarely sight-threatening, the quality of life for myopic patients is negatively affected and the health care costs to treat myopia are astronomical (approximately $4.6 billion in 1990). The National Eye Institute recognizes the need to "evaluate the efficacy of potential treatments for delaying the onset or for slowing the progression of myopia, such as lenses that alter peripheral defocus."

Using a common treatment of myopia (contact lenses) to potentially slow myopia progression and to learn about optical signals that regulate eye growth is a very novel approach to solving a problem that affects a large proportion of people in the United States.

Study Design

• Study Type: Interventional
• Actual Enrollment: 294 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Soft Bifocal Contact Lens Myopia Control
• Actual Study Start Date: Sep 22, 2014
• Actual Primary Completion Date: Jun 24, 2019
• Actual Study Completion Date: Jun 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Biofinity Soft spherical contact lens	Device: Biofinity; This is a monthly disposable spherical contact lens commercially available from CooperVision
Experimental: Biofinity Multifocal D +1.50 add The Biofinity Multifocal "D" with a +1.50 add is a soft bifocal contact lens that has a medium reading power	Device: Biofinity Multifocal D +1.50 add; This is a monthly disposable contact lens commercially available from CooperVision
Experimental: Biofinity Multifocal D +2.50 add The Biofinity Multifocal "D" with a +2.50 add is a soft bifocal contact lens that has a strong reading power	Device: Biofinity Multifocal D +2.50 add; This is a monthly disposable contact lens commercially available from CooperVision

Outcome Measures

Primary Outcome Measures

1. Refractive Error Progression [3 years]

   Refractive error, as measured by cycloplegic autorefraction in both eyes, will be measured yearly to assess the difference in progression between the two soft bifocal treatment lenses (+1.50 D add and +2.50 D add) and the control group (soft spherical contact lenses).

Secondary Outcome Measures

1. Ocular Shape Change and Eye Growth [3 years]

   The outcome of interest is the change in ocular shape and measured by the change in peripheral refractive error in the right eye. The change in peripheral refractive error will be compared among the two treatment groups and the control group to determine whether peripheral defocus changes the shape of the eye globally (across the whole eye) or locally (specific to the region of the eye affected by the defocus).

2. Association of Peripheral Defocus to Myopic Progression [3 years]

   Peripheral defocus will be measured in 10 areas (Nasal and temporal zones at 20, 30, and 40 degrees, and superior and inferior zones at 20 and 30 degrees) and analyzed for its relation to myopia progression (as measured by cycloplegic autorefraction in the right eye only).

3. Axial Length Progression [3 years]

   Axial length progression, as measured by Lenstar in both eyes, will be measured yearly to assess the difference in progression between the two soft bifocal treatment lenses (+1.50 D add and +2.50 D add) and the control group (soft spherical contact lenses).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 7 to 11 years, inclusive, at baseline examination

• -0.75 to -5.00 D, inclusive, spherical component, cycloplegic autorefraction

• ≤1.00 DC, cycloplegic autorefraction

• ≥ 2.00 D difference between the sphere components of the two eyes (anisometropia), cycloplegic autorefraction

• 0.1 logMAR or better best-corrected visual acuity in each eye

• 0.1 logMAR or better visual acuity OU distance and near with a +2.50 D add contact lens

• +2.50 D add lens provides adequate fit with respect to movement and centration

Exclusion Criteria:

• Eye disease or binocular vision problems (e.g., strabismus, amblyopia, oculomotor nerve palsies, corneal disease, etc.)

• Systemic disease that may affect vision, vision development, or contact lens wear (eg, diabetes, Down syndrome, etc.)

• Previous gas permeable, soft bifocal, or orthokeratology contact lens wear or bifocal/PAL spectacle wear (longer than 1 month of wear)

• Previous or current participation in myopia control studies

• Chronic use of medications that may affect immunity, such as oral or ophthalmic corticosteroids for ocular or systemic diseases

• Issues that may interfere with the ability to participate over the next 3 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University College of Optometry	Columbus	Ohio	United States	43210
2	University of Houston College of Optometry	Houston	Texas	United States	77204

Sponsors and Collaborators

• Ohio State University
• University of Houston
• National Eye Institute (NEI)

Investigators

• Study Chair: Jeffrey Walline, OD, PhD, Ohio State University

Study Documents (Full-Text)

• Informed Consent Form: University of Houston Informed Consent - Aug 1, 2014
• Study Protocol and Statistical Analysis Plan - May 31, 2018
• Informed Consent Form: Ohio State University Clinical Site - Nov 5, 2015

More Information

Publications

None provided.

• Responsible Party: Jeffrey J. Walline, OD PhD, Associate Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT02255474
• Other Study ID Numbers: 2014H0231; U10EY023208
• First Posted: Oct 2, 2014
• Last Update Posted: Mar 10, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Jeffrey J. Walline, OD PhD, Associate Professor, Ohio State University: pediatrics; refractive error - myopia; contact lenses; intervention
• Additional relevant MeSH terms: Refractive Errors

Study Results

Participant Flow

Arm/Group Title	Biofinity	Biofinity Multifocal D +1.50 Add	Biofinity Multifocal D +2.50 Add
Arm/Group Description	Soft spherical contact lens Biofinity: This is a monthly disposable spherical contact lens commercially available from CooperVision	The Biofinity Multifocal "D" with a +1.50 add is a soft bifocal contact lens that has a medium reading power Biofinity Multifocal D +1.50 add: This is a monthly disposable contact lens commercially available from CooperVision	The Biofinity Multifocal "D" with a +2.50 add is a soft bifocal contact lens that has a strong reading power Biofinity Multifocal D +2.50 add: This is a monthly disposable contact lens commercially available from CooperVision
Period Title: Overall Study
STARTED	98	98	98
COMPLETED	96	96	95
NOT COMPLETED	2	2	3

Baseline Characteristics

Arm/Group Title	Biofinity	Biofinity +1.50 D Add	Biofinity +2.50 D Add	Total
Arm/Group Description	Single vision soft contact lens	Medium add soft bifocal contact lens (+1.50 Diopter add)	High add soft bifocal contact lens (+2.50 Diopter add)	Total of all reporting groups
Overall Participants	98	98	98	294
Age (Count of Participants)
<=18 years	98 100%	98 100%	98 100%	294 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.3 (1.1)	10.3 (1.2)	10.36 (1.2)	10.3 (1.2)
Age, Customized (Count of Participants)
7 to 9 years	39 39.8%	39 39.8%	39 39.8%	117 39.8%
10 to 11 years	59 60.2%	59 60.2%	59 60.2%	177 60.2%
Sex: Female, Male (Count of Participants)
Female	64 65.3%	49 50%	64 65.3%	177 60.2%
Male	34 34.7%	49 50%	34 34.7%	117 39.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	25 25.5%	26 26.5%	26 26.5%	77 26.2%
Not Hispanic or Latino	72 73.5%	71 72.4%	71 72.4%	214 72.8%
Unknown or Not Reported	1 1%	1 1%	1 1%	3 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%	1 1%	3 3.1%	5 1.7%
Asian	9 9.2%	7 7.1%	9 9.2%	25 8.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 1%	1 0.3%
Black or African American	17 17.3%	7 7.1%	5 5.1%	29 9.9%
White	59 60.2%	75 76.5%	66 67.3%	200 68%
More than one race	11 11.2%	7 7.1%	13 13.3%	31 10.5%
Unknown or Not Reported	1 1%	1 1%	1 1%	3 1%
Region of Enrollment (participants) [Number]
United States	98 100%	98 100%	98 100%	294 100%
Site (Count of Participants)
Columbus, OH	49 50%	48 49%	46 46.9%	143 48.6%
Houston, TX	49 50%	50 51%	52 53.1%	151 51.4%
Spherical equivalent (Diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Diopters]	-2.46 (0.97)	-2.43 (1.11)	-2.28 (0.90)	-2.39 (1.00)
Axial length (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	24.45 (0.83)	24.57 (0.85)	24.43 (0.74)	24.48 (0.81)
Peripheral axial length (mm) [Mean (Standard Deviation) ]
20 degree inferior	24.27 (0.83)	24.37 (0.85)	24.24 (0.74)	24.29 (0.81)
20 degree nasal	24.16 (0.85)	24.31 (0.95)	24.15 (0.86)	24.20 (0.88)
20 degree superior	24.38 (0.84)	24.45 (0.85)	24.36 (0.79)	24.40 (0.82)
20 degree temporal	24.07 (0.85)	24.20 (0.84)	24.06 (0.74)	24.11 (0.81)
30 degree inferior	24.03 (0.81)	24.13 (0.82)	24.01 (0.72)	24.06 (0.78)
30 degree nasal	24.08 (0.85)	24.22 (0.87)	24.07 (0.79)	24.13 (0.84)
30 degree superior	24.20 (0.86)	24.25 (0.86)	24.19 (0.80)	24.21 (0.84)
30 degree temporal	23.69 (0.820)	23.82 (0.80)	23.69 (0.73)	23.73 (0.79)
Peripheral defocus (Diopters) [Mean (Standard Deviation) ]
40 degree nasal	2.17 (1.17)	1.07 (1.30)	0.44 (1.23)	1.23 (1.42)
30 degree nasal	1.06 (0.84)	0.16 (1.02)	-0.37 (0.95)	0.28 (1.10)
20 degree nasal	0.54 (0.81)	-0.10 (0.77)	-0.37 (0.75)	0.02 (0.86)
20 degree temporal	0.56 (0.75)	-0.27 (0.79)	-0.86 (0.74)	-0.19 (0.96)
30 degree temporal	1.29 (1.06)	0.27 (1.07)	-0.35 (1.21)	0.40 (1.30)
40 degree temporal	1.92 (1.64)	1.33 (1.71)	0.87 (1.64)	1.37 (1.72)

Outcome Measures

1. Primary Outcome

Title	Refractive Error Progression
Description	Refractive error, as measured by cycloplegic autorefraction in both eyes, will be measured yearly to assess the difference in progression between the two soft bifocal treatment lenses (+1.50 D add and +2.50 D add) and the control group (soft spherical contact lenses).
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biofinity	Biofinity +1.50 D Add	Biofinity +2.50 D Add
Arm/Group Description	Spherical soft contact lens	Medium add soft bifocal contact lens (+1.50 Diopter add)	High add soft bifocal contact lens (+2.50 Diopter add)
Measure Participants	97	98	97
Mean (Standard Deviation) [Diopters]	-3.46 (1.20)	-3.32 (1.48)	-2.84 (1.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Biofinity, Biofinity +1.50 D Add, Biofinity +2.50 D Add
	Comments	Both eyes used in analysis adjusting for correlation.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments	Adjusted for multiple comparisons, treatment group p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Ocular Shape Change and Eye Growth
Description	The outcome of interest is the change in ocular shape and measured by the change in peripheral refractive error in the right eye. The change in peripheral refractive error will be compared among the two treatment groups and the control group to determine whether peripheral defocus changes the shape of the eye globally (across the whole eye) or locally (specific to the region of the eye affected by the defocus).
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Analysis of peripheral eye length changes with treatment

Arm/Group Title	Biofinity	Biofinity +1.50 D Add	Biofinity +2.50 D Add
Arm/Group Description	Single vision soft contact lens	Medium add soft bifocal contact lens (+1.50 Diopter add)	High add soft bifocal contact lens (+2.50 Diopter add)
Measure Participants	97	98	97
20 degree inferior	24.92 (0.85)	24.94 (0.97)	24.64 (0.79)
20 degree nasal	24.86 (0.87)	24.90 (1.09)	24.60 (0.93)
20 degree superior	24.98 (0.89)	24.98 (0.97)	24.74 (0.84)
20 degree temporal	24.98 (0.89)	24.98 (0.97)	24.71 (0.84)
30 degree inferior	24.64 (0.83)	24.68 (0.94)	24.45 (0.78)
30 degree nasal	24.70 (0.84)	24.79 (1.01)	24.51 (0.87)
30 degree superior	24.76 (0.92)	247.77 (0.95)	24.58 (0.86)
30 degree temporal	24.30 (0.82)	24.29 (0.91)	24.04 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Biofinity, Biofinity +1.50 D Add
	Comments	Individual subject eye length profiles were fit using quadratic equations as a function of gaze angle. The analysis of quadratic coefficients included treatment group, study year (categorical variable), and their interaction adjusted for age, study site, and ethnicity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	quadratic coefficient
	Estimated Value	0.02
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Association of Peripheral Defocus to Myopic Progression
Description	Peripheral defocus will be measured in 10 areas (Nasal and temporal zones at 20, 30, and 40 degrees, and superior and inferior zones at 20 and 30 degrees) and analyzed for its relation to myopia progression (as measured by cycloplegic autorefraction in the right eye only).
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

outcome is three-year change in refractive error as a function of baseline peripheral defocus

Arm/Group Title	Biofinity	Biofinity +1.50 D Add	Biofinity +2.50 D Add
Arm/Group Description	Single vision soft contact lens	Medium add soft bifocal contact lens (+1.50 Diopter add)	High add soft bifocal contact lens (+2.50 Diopter add)
Measure Participants	97	98	97
Mean (Standard Deviation) [Diopters]	-1.01 (0.66)	-0.85 (0.82)	-0.56 (0.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Biofinity, Biofinity +1.50 D Add, Biofinity +2.50 D Add
	Comments	This analysis looks at the three-year change in spherical equivalent refractive error for different eccentricities of peripheral defocus measured with contact lenses in place
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Regression, Linear
	Comments	Models control for age, sex, axial length at baseline, race, treatment group, treatment group by race interaction.
Method of Estimation	Estimation Parameter	regression coefficient
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Axial Length Progression
Description	Axial length progression, as measured by Lenstar in both eyes, will be measured yearly to assess the difference in progression between the two soft bifocal treatment lenses (+1.50 D add and +2.50 D add) and the control group (soft spherical contact lenses).
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biofinity	Biofinity +1.50 D Add	Biofinity +2.50 D Add
Arm/Group Description	Spherical soft contact lens	Medium add soft bifocal contact lens (+1.50 Diopter add)	High add soft bifocal contact lens (+2.50 Diopter add)
Measure Participants	97	98	97
Mean (Standard Deviation) [mm]	25.08 (0.85)	25.12 (0.97)	24.81 (0.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Biofinity, Biofinity +1.50 D Add, Biofinity +2.50 D Add
	Comments	Both eyes used in the analysis controlling for the correlation.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Adjusted for multiple comparisons
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Three years
Adverse Event Reporting Description	Any event, ocular or non-ocular, regardless of relation to contact lens wear that occurred.
Arm/Group Title	Biofinity		Biofinity +1.50 D Add		Biofinity +2.50 D Add
Arm/Group Description	Spherical soft contact lens		Medium add soft bifocal contact lens (+1.50 Diopter add)		High add soft bifocal contact lens (+2.50 Diopter add)
All Cause Mortality
	Biofinity		Biofinity +1.50 D Add		Biofinity +2.50 D Add
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/98 (0%)		0/98 (0%)
Serious Adverse Events
	Biofinity		Biofinity +1.50 D Add		Biofinity +2.50 D Add
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/98 (0%)		0/98 (0%)
Other (Not Including Serious) Adverse Events
	Biofinity		Biofinity +1.50 D Add		Biofinity +2.50 D Add
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/97 (74.2%)		71/98 (72.4%)		75/97 (77.3%)
Eye disorders
SEAL	3/97 (3.1%)	3	1/98 (1%)	1	1/97 (1%)	1
CLARE	1/97 (1%)	1	1/98 (1%)	1	2/97 (2.1%)	2
Corneal epithelial defect	2/97 (2.1%)	2	2/98 (2%)	2	5/97 (5.2%)	5
Infiltrative keratitis	5/97 (5.2%)	6	4/98 (4.1%)	5	2/97 (2.1%)	2
Probable microbial keratitis	0/97 (0%)	0	0/98 (0%)	0	1/97 (1%)	1
Sterile Corneal Ulcer	1/97 (1%)	1	1/98 (1%)	1	0/97 (0%)	0
Toxic exposure	4/97 (4.1%)	4	3/98 (3.1%)	3	0/97 (0%)	0
Giant papillary conjunctivitis	3/97 (3.1%)	3	5/98 (5.1%)	5	3/97 (3.1%)	3
Ocular allergies	9/97 (9.3%)	9	12/98 (12.2%)	12	22/97 (22.7%)	25
Blepharitis	0/97 (0%)	0	1/98 (1%)	1	2/97 (2.1%)	2
Hordeolum/chalazion	9/97 (9.3%)	10	3/98 (3.1%)	3	7/97 (7.2%)	10
Eyelash issue	1/97 (1%)	1	0/98 (0%)	0	0/97 (0%)	0
Ptosis	1/97 (1%)	1	0/98 (0%)	0	0/97 (0%)	0
Corneal scar, new	3/97 (3.1%)	4	5/98 (5.1%)	6	4/97 (4.1%)	5
Solution induced corneal staining	28/97 (28.9%)	28	35/98 (35.7%)	35	28/97 (28.9%)	28
Poor contact lens fit	1/97 (1%)	1	0/98 (0%)	0	1/97 (1%)	1
Foreign body	2/97 (2.1%)	2	0/98 (0%)	0	1/97 (1%)	1
Dry eye	5/97 (5.2%)	5	3/98 (3.1%)	3	5/97 (5.2%)	5
Contact lens solution issue	3/97 (3.1%)	3	2/98 (2%)	2	5/97 (5.2%)	5
Conjunctivitis, any type	5/97 (5.2%)	5	5/98 (5.1%)	5	5/97 (5.2%)	5
Subconjunctival hemorrhage	3/97 (3.1%)	3	2/98 (2%)	2	3/97 (3.1%)	3
Retinal issue	4/97 (4.1%)	4	2/98 (2%)	2	4/97 (4.1%)	4
Optic nerve issue	1/97 (1%)	1	1/98 (1%)	1	0/97 (0%)	0
Uveitis	1/97 (1%)	1	0/98 (0%)	0	0/97 (0%)	0
Trauma, ocular	1/97 (1%)	1	0/98 (0%)	0	3/97 (3.1%)	3
Binocular vision/accommodation issue	5/97 (5.2%)	5	1/98 (1%)	1	5/97 (5.2%)	5
Color vision defect	0/97 (0%)	0	1/98 (1%)	1	0/97 (0%)	0
Transient visual disturbance	0/97 (0%)	0	2/98 (2%)	2	0/97 (0%)	0
Unspecified contact lens issue	1/97 (1%)	1	2/98 (2%)	2	3/97 (3.1%)	3
Visual symptoms, no obvious cause	0/97 (0%)	0	1/98 (1%)	1	1/97 (1%)	1
General disorders
Trauma, non-ocular	19/97 (19.6%)	21	12/98 (12.2%)	13	7/97 (7.2%)	9
Headaches	6/97 (6.2%)	7	3/98 (3.1%)	3	6/97 (6.2%)	7
Concussion	1/97 (1%)	1	1/98 (1%)	1	4/97 (4.1%)	4
Systemic disease	8/97 (8.2%)	8	9/98 (9.2%)	9	10/97 (10.3%)	12
Can't categorize	1/97 (1%)	1	1/98 (1%)	1	0/97 (0%)	0
Immune system disorders
Allergy, non-ocular	3/97 (3.1%)	3	1/98 (1%)	1	0/97 (0%)	0
Psychiatric disorders
Mental health issues	4/97 (4.1%)	4	2/98 (2%)	2	2/97 (2.1%)	2

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.