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

March 9, 2022 updated by: Theodore Heyming, Children's Hospital of Orange County
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

130

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • CHOC Children's
        • Contact:
        • Contact:
        • Sub-Investigator:
          • William Loudon, MD PhD
        • Sub-Investigator:
          • Sharief Taraman, MD
        • Sub-Investigator:
          • Jennifer Hayakawa, DNP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of concussed patients ages 5-17 presenting at a pediatric emergency department within 72 hours following concussion and healthy controls that are age and gender matched to concussed subjects recruited from affiliated primary care and adolescent clinics.

Description

Inclusion Criteria:

  1. Males or females ≥ 5 to < 18 years of age
  2. 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)
  3. Age and gender matched healthy controls recruited and evaluated through Primary Care (Orange Ambulatory) and Adolescent Clinics

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The association between NPi®-200 pupillometer measurements (including variables such as size, latency, constriction velocity, dilation velocity, etc.) and concussed/control status over time.
Time Frame: 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.
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 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.
Time Frame: 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.
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 association between the Post-Concussion Symptom Inventory (PCSI) & Post-Concussion Symptom Scale (PCSS) and concussed/control status over time.
Time Frame: 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.
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 association between the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®) & ImPACT® Pediatric assessment and concussed/control status over time.
Time Frame: 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.
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 association between the Balance Error Scoring System (BESS) scores and concussed/control status over time.
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Orange County

Collaborators

NeurOptics Inc.

Investigators

  • Principal Investigator: Theodore Heyming, MD, CHOC Children's Hospital of Orange County

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2020

Primary Completion (Anticipated)

September 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

February 27, 2020

First Submitted That Met QC Criteria

September 1, 2020

First Posted (Actual)

September 7, 2020

Study Record Updates

Last Update Posted (Actual)

March 11, 2022

Last Update Submitted That Met QC Criteria

March 9, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1909112

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is not a plan to make IPD available as data may be proprietary in nature.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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