Clinical trial NCT04540445: Utility of Pupillary Metrics in Diagnosis and Management of Concussion in Children
Official title: Utility of Pupillary Metrics in Diagnosis and Management of Concussion in Children
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Brain Concussion
Reflex, Pupillary
Post-Concussion Syndrome
Brain Injuries, Traumatic
Keywords: pupillometry
concussion
traumatic brain injury
post-concussion syndrome
Lead sponsor: Children's Hospital of Orange County
Sponsor class: OTHER
Collaborators: name: NeurOptics Inc.
First posted: 2020-09-07
Enrollment: 130
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The association between NPi®-200 pupillometer measurements (including variables such as size, latency, constriction velocity, dilation velocity, etc.) and concussed/control status over time.
timeFrame: 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.
measure: 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.
timeFrame: 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.
measure: The association between the Post-Concussion Symptom Inventory (PCSI) & Post-Concussion Symptom Scale (PCSS) and concussed/control status over time.
timeFrame: 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.
measure: The association between the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®) & ImPACT® Pediatric assessment and concussed/control status over time.
timeFrame: 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.
measure: The association between the Balance Error Scoring System (BESS) scores and concussed/control status over time.
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: CHOC Children's
state: California
Study officials:
affiliation: CHOC Children's Hospital of Orange County
name: Theodore Heyming, MD
role: PRINCIPAL_INVESTIGATOR
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