Utility of Pupillary Metrics in Diagnosis and Management of Concussion in Children

Sponsor

Children's Hospital of Orange County (Other)

Overall Status

Recruiting

CT.gov ID

NCT04540445

Collaborator

NeurOptics Inc. (Industry)

130

Enrollment

Location

32.7

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to gather information and compare the potential use of pupillometry to identify concussions and post concussive syndrome with standard age appropriate assessments. The study will compare concussed pediatric patients 5-17 years of age recruited from the emergency department within 72 hours following injury with age and gender matched non-concussed pediatric patients recruited from primary care clinics. Assessment of both concussed and non-concussed subjects will take place at the initial enrollment visit and will be repeated at 1-2 weeks for the concussed subjects and at 12-14 weeks for both groups.

Condition or Disease	Intervention/Treatment	Phase
Brain Concussion Reflex, Pupillary Post-Concussion Syndrome Brain Injuries, Traumatic	Other: Pupillary Assessment

Detailed Description

Traumatic brain injury (TBI) is the leading cause of disability and death in children. In both pediatric and adult populations, concussion is the most prevalent type of TBI and can result in persistent post-concussive symptoms. Early recognition and treatment of concussion is critical to the prevention of long-term sequelae and has recently become a national public-health priority. Comprehensive assessment and diagnosis of concussion commonly includes the use of a multimodal approach using a graded symptoms checklist, neurocognitive testing, and balance assessment. An objective biomarker to definitively diagnose concussion would revolutionize its management-allowing for accurate and immediate determination of return to play/duty, decreasing unnecessary exposure to radiation, and reducing the overall cost of care. Considering the paucity of evidence regarding the use of pupillary light reflex in concussed children and the lack of a biomarker for concussion, further examination of the use of objective pupillary metrics in this population is warranted.

The purpose of this study is to gather information and compare the potential use of pupillometry to identify concussions and post concussive syndrome with standard age appropriate assessments. The proposed study design is prospective, longitudinal case-control consisting of two distinct cohorts: concussed participants and healthy control participants. All concussion management decisions will be determined independent of the study by the healthcare provider(s). Trained personnel performing follow-up assessments will use established clinical criteria to notify appropriate healthcare provider and/or study team member of any clinical concerns or unanticipated events.

The study will compare concussed pediatric patients 5-17 years of age recruited from the emergency department within 72 hours following injury with age and gender matched non-concussed pediatric patients recruited from affiliated primary care and adolescent clinics. Assessment of both concussed and non-concussed subjects will take place at the initial enrollment visit and will be repeated at 1-2 weeks for the concussed subjects and at 12-14 weeks for both groups. Age appropriate assessment will include the Post-Concussion Symptom Inventory (PCSI), Post-Concussion Symptom Scale (PCSS), pupillometry, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), and Balance Error Scoring System (BESS).

The primary objectives are to examine the acute (<72 hours), subacute (1-2 week), and long-term (12-14 weeks post-injury) longitudinal association among pupillary metrics, standardized neurocognitive tests, and objective balance assessment in pediatric patients with concussion versus controls. The secondary objectives are to evaluate the effectiveness of pupillometer data as an objective biomarker to aid in the identification of concussion and post-concussive syndrome in children. Results will generate new knowledge regarding the clinical utility of pupillometers in this patient population. We will explore the period that best differentiates concussion and controls.

Study Design

Study Type:

Observational

Anticipated Enrollment :

130 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Utility of Pupillary Metrics in Diagnosis and Management of Concussion in Children

Actual Study Start Date :

Mar 11, 2020

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Concussed Cohort The concussed cohort will consist of children ages 5-17 diagnosed with a concussion within 72 hours following injury and recruited from a pediatric emergency department.	Other: Pupillary Assessment Pupillary assessment with handheld pupillometer Other Names: NeurOptics PLR-3000 NeurOptics NPi®-200
Healthy Matched Controls The healthy matched control cohort consists of children 5-17, who are age and gender matched to concussed subjects who will be recruited from affiliated pediatric primary care and adolescent clinics.	Other: Pupillary Assessment Pupillary assessment with handheld pupillometer Other Names: NeurOptics PLR-3000 NeurOptics NPi®-200

Arm

Intervention/Treatment

Concussed Cohort

The concussed cohort will consist of children ages 5-17 diagnosed with a concussion within 72 hours following injury and recruited from a pediatric emergency department.

Other: Pupillary Assessment

Pupillary assessment with handheld pupillometer

Other Names:

NeurOptics PLR-3000

NeurOptics NPi®-200

Healthy Matched Controls

The healthy matched control cohort consists of children 5-17, who are age and gender matched to concussed subjects who will be recruited from affiliated pediatric primary care and adolescent clinics.

Other: Pupillary Assessment

Pupillary assessment with handheld pupillometer

Other Names:

NeurOptics PLR-3000

NeurOptics NPi®-200

Outcome Measures

Primary Outcome Measures

The association between NPi®-200 pupillometer measurements (including variables such as size, latency, constriction velocity, dilation velocity, etc.) and concussed/control status over time. [For concussed subjects: the first measurement will be within 72 hours of sustaining injury, then repeated at 1-2 weeks and at 12-14 weeks post injury. For control subjects: the first measurement will be at enrollment and repeated at 12-14 weeks.]
NPi®-200 pupillometer is a hand-held portable infrared device which provides quantitative pupillary measurements by taking 30 pictures per second of the pupil's response to light stimulus for a duration of 3 seconds. A patient's pupil measurement (including variables such as size, latency, constriction velocity, dilation velocity, etc.) is compared against a normative model of pupil reaction to light and automatically graded by the Neurological Pupil Index (NPi™) on a scale of 0 to 5. Pupillary measurements will be obtained for the right and left eye.
The association between the NeurOptics PLR-3000 pupillometer measurements (including variables such as size, latency, constriction velocity, dilation velocity, etc.) and concussed/control status over time. [For concussed subjects: the first measurement will be within 72 hours of sustaining injury, then repeated at 1-2 weeks and at 12-14 weeks post injury. For control subjects: the first measurement will be at enrollment and repeated at 12-14 weeks.]
The NeurOptics PLR-3000 pupillometer is a hand-held portable infrared device which provides quantitative pupillary measurements by taking 30 pictures per second of the pupil's response to light stimulus for a duration of 6 seconds. Pupillary data, such as constriction velocity, latency, pupil size before and after the reflex, dilation velocity, time to reach 75% of initial resting diameter after constriction (T75) are calculated automatically at the end of each measurement. Pupillary measurements will be obtained for the right and left eye.
The association between the Post-Concussion Symptom Inventory (PCSI) & Post-Concussion Symptom Scale (PCSS) and concussed/control status over time. [For concussed subjects: the first measurement will be within 72 hours of sustaining injury, then repeated at 1-2 weeks and at 12-14 weeks post injury. For control subjects: the first measurement will be at enrollment and repeated at 12-14 weeks.]
PCSI assesses post-concussion symptoms based on patient and parent/teacher report. This inventory focuses on four areas that may be affected after concussion: cognitive, emotional, physical, and sleep. There are age-specific forms available for children between 5-7 years old, 8-12 years old, and 13-18 years old. This tool has been found to have moderate to high (0.62 to 0.84) inter-rater reliability for child reports and internal consistency across the three reports. PCSS is also a self-reported assessment of post-concussion symptoms. This report, which is part of the widely used Sport Concussion Assessment Tool (SCAT) Versions 3 and 5 and Immediate Post-Concussion Assessment and Cognitive Test (ImPACT), quantifies symptom severity (rank 22 different possible post-concussion symptoms on 7 point Likert scale). Similar to the PCSI, the PCSS includes symptoms from four areas: cognitive, emotional, physical, and sleep.
The association between the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®) & ImPACT® Pediatric assessment and concussed/control status over time. [For concussed subjects: the first measurement will be within 72 hours of sustaining injury, then repeated at 1-2 weeks and at 12-14 weeks post injury. For control subjects: the first measurement will be at enrollment and repeated at 12-14 weeks.]
ImPACT® and ImPACT® Pediatric will both be used in this study. ImPACT® is a computerized data collection and neuropsychological testing tool commonly used for baseline and post-injury testing in athletes (12-59 years of age) at risk for sports-related concussion. Subjects participate in neuropsychological tests which assess attention, verbal memory, visual memory, visual processing speed, and reaction times. ImPACT® will be used to evaluate study patients ≥12 years old. ImPACT® Pediatric is an examiner-administered iOS-based battery of neuropsychological tests designed to measure neurocognitive functioning in children ages 5-11. ImPACT® Pediatric is administered on an iPad and is a neurocognitive test for management of pediatric concussions. ImPACT® Pediatric will be used to evaluate patients < 12 years old. Outcome variables will be obtained from ImPACT® and include data to evaluate: verbal memory, visual memory, visual processing speed, and reaction time.
The association between the Balance Error Scoring System (BESS) scores and concussed/control status over time. [For concussed subjects: the first measurement will be within 72 hours of sustaining injury, then repeated at 1-2 weeks and at 12-14 weeks post injury. For control subjects: the first measurement will be at enrollment and repeated at 12-14 weeks.]
The Balance Error Scoring System (BESS) provides an objective score for a patient's postural stability. The patient is instructed to stand in three different stances, first on a solid surface and then a foam surface, for 20 seconds each. The examiner records the number of errors, as predefined by the scoring system, during each stance. The maximum score is 60 and a higher score correlates with worsening postural stability. This test has demonstrated good test-rest reliability (0.87-0.97 intraclass correlations), low to moderate sensitivity (0.34 to 0.64), and high specificity (0.91). Sensitivity is increased when this test is used in conjunction with a graded symptom checklist.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Males or females ≥ 5 to < 18 years of age
Patients presenting to Pediatric Emergency Department with a concussion within 72 hours following injury. Concussion will be defined as the presence of the following criteria: Post injury patient reported symptoms on an age-appropriate graded-symptom checklist that meets the borderline to extremely high threshold (sex and age adjusted)
Age and gender matched healthy controls recruited and evaluated through Primary Care (Orange Ambulatory) and Adolescent Clinics

Exclusion Criteria:

Lower extremity deficiency or injury
History of cognitive deficiencies
History of ≥ 3 prior concussions
History of attention deficit disorder
Previously diagnosed concussion within the past year
History of intracranial disease
History of unresolved strabismus, diplopia, amblyopia
History of unresolved cranial nerve III, IV or VI palsy
History of unresolved macular edema, retinal degeneration, extensive cataract, or ocular globe disruption
History of unresolved extensive corneal surgery or scarring
Lack of two functional eyes
Unresolved oculo-motor dysfunctions
Obvious intoxication or impairment that limits ability to participate
Imaging abnormality (i.e. fracture or bleed)
Color blindness OR failing the Ishihara screening for color blindness
Unable to come in for follow-up visits
In addition to the above exclusion criteria, healthy control participants will be excluded if they have a history of chronic disease.