Clinical trial NCT05825027: Risk Stratification in Children With Concussion
Official title: A Risk Stratification Model for Health and Academic Outcomes in Children With Concussion Based on Novel Symptom Trajectory Typologies
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Concussion, Brain
Mild Traumatic Brain Injury
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2023-04-24
Enrollment: 500
Sex: ALL
Minimum age (years): 11
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be recruited from concussion clinics in the Raleigh-Durham metro area of North Carolina.

Brief summary: This project will measure concussion symptoms, biological markers, and academic and social factors across the first year postconcussion to develop a model that enables early identification of and symptom management for children at higher risk for persistent postconcussive symptoms. Findings will provide novel insights into the longer-term effects of concussion on children's physical, psychological, and social well-being and support the development of personalized healthcare and school-based plans to reduce disparities in children's ability to return-to-learn and -play and improve postconcussion quality of life.

Detailed description: Concussions occur at an alarming rate among U.S. schoolchildren, with one in five children experiencing a concussion by age 16. The number of children visiting emergency departments for concussions annually has increased by 50% over the past decade, with an estimated cost to the healthcare system of $1 billion/year. Compared to adults, children experience longer and more severe postconcussive symptoms (PCS). Severity and duration of PCS, however, vary considerably among children, complicating clinical care and return to learn and play. Persistent PCS including physical, emotional, and cognitive symptoms, result in increased school absenteeism, social isolation, and psychological distress. Early PCS diagnosis and access to evidence-based return-to-health and -school interventions are strongly linked to positive health and academic outcomes. Yet models to identify children at high risk for persistent PCS are lacking. PCS have been linked to inflammatory processes occurring within the injured brain. Preliminary evidence suggests that fatigue, another symptom likely contributing to poor outcomes, is also a biological byproduct of pediatric concussions. Importantly, even though 73% of children report continuous fatigue after concussion, this symptom is rarely studied along with other PCS. Prior research has focused on the relationship between inflammatory biomarkers and PCS severity but has not examined this relationship longitudinally. Acute symptom severity alone, however, is a poor prognostic of clinical outcomes in concussed children. Symptom severity immediately postinjury does not explain why at least 25% of children still experience PCS after 1 year or why even children who may appear asymptomatic still report academic and social challenges months after concussion. To identify which children are at high risk for persistent PCS and poor health, academic, and social outcomes, research tracking PCS trajectories and describing school-based impacts across the entire first year postinjury is critically needed. This proposal will 1) define novel PCS trajectory typologies in a racially/ethnically diverse population of 500 children with concussion (11-17 years, near equal distribution by sex), 2) identify associations between these typologies and patterns of inflammatory biomarkers, 3) develop a risk stratification model to identify children at risk for persistent PCS; and 4) gain unique insights and describe PCS impact, including fatigue, on longer-term academic and social outcomes. We will be the first to use NIH's symptom science model and patient-reported outcomes to explore the patterns of fatigue and other physical, cognitive, psychological, emotional and academic responses to concussion in children over a full year. Our model will enable clinicians and educators to identify children most at risk for poor long-term health, social, and academic outcomes after concussion. This work is critical to meeting our long-term goal of developing personalized concussion symptom management strategies to improve outcomes and reduce disparities in the health and quality of life of children.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with concussion that occurred within the past 7 days
* Glasgow Coma Scale (GCS) score between 13-15
* English speaking

Exclusion Criteria:

* Diagnosed with moderate or severe traumatic brain injury
* Polytrauma
* Nontraumatic brain injury
* Pregnancy

Primary outcomes:
measure: Change in concussion symptom burden and severity as measured by the Post Concussion Symptom Scale (PCSS)
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Change in post concussion fatigue burden and severity as measured by the PROMIS Pediatric Item Bank v2.0 - Fatigue
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Change in degree of involvement with one's peers in usual social roles, activities and responsibilities as measured by the Neuro-QoL Item Bank v1.0 - Pediatric Social Relations - Interaction with Peers
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Change in perceived difficulties in everyday cognitive abilities such as memory, attention, concentration, processing speed and organization skill as measured by the Neuro-QoL Item Bank v2.0 - Pediatric Cognitive Function
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Change in academic needs of a student following concussion as measured by the Concussion Learning Assessment & School Survey, 3rd Edition (CLASS-3)
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Salivary Interferon Gamma
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Salivary Interleukin-1 Beta
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Salivary Interleukin-6
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Salivary Interleukin-8
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Salivary Interleukin-10
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Salivary TNF-Alpha
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Pubertal status
timeFrame: Within 7 days of injury, 30 days post injury, 90 days post injury, 180 days post injury, 270 days post injury and 360 days post injury
measure: Presence of genetic variants in genes that code for inflammatory cytokines
timeFrame: Within 7 days of injury
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke University School of Nursing
name: Karin Reuter-Rice, PhD
role: PRINCIPAL_INVESTIGATOR
References: