Epigenetic Effects on Traumatic Brain Injury Recovery

NCT04186429 | Completed

• 2 other identifiers: STUDY190404021K01HD097030-01A1
• Study Type: observational
• Target: 401
• Locations: 1 country
• Sites: 1

Brief Summary

Methylation of the brain-derived neurotrophic factor (BDNF) gene is involved in both the biological encoding of childhood adversity and neuroplasticity following traumatic brain injury (TBI). This research will characterize BDNF methylation during recovery from TBI in children and investigate this novel biomarker as a potential biological mechanism underlying the known association between childhood adversity and poorer neurobehavioral outcomes following TBI in childhood. Findings from this research will contribute to an improved understanding of why some children display good recovery following TBI, whereas many others suffer from chronic neurobehavioral impairments.

Conditions

Traumatic Brain Injury; Orthopedic Injury

Keywords

traumatic brain injury; rehabilitation; neuropsychology; precision medicine; epigenetic; proteomic; brain-derived neurotrophic factor; recovery; neurobehavioral outcomes; children; childhood adversity; biomarkers

Outcome Measures

Primary Outcomes (8)

• NIH Toolbox Cognition Battery (NIHTB-CB)

  The NIHTB-CB is a 30-minute battery of standardized neuropsychological tests administered on an iPad. The NIHTB-CB provides norm-referenced scores for the domains of language, episodic memory, processing speed, working memory, and executive function, as well as an overall cognitive function composite score. Higher T scores indicate better neuropsychological performance.

  6 months post-injury

• NIH Toolbox Cognition Battery (NIHTB-CB)

  The NIHTB-CB is a 30-minute battery of standardized neuropsychological tests administered on an iPad. The NIHTB-CB provides norm-referenced scores for the domains of language, episodic memory, processing speed, working memory, and executive function, as well as an overall cognitive function composite score. Higher T scores indicate better neuropsychological performance.

  12 months post-injury

• Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P)

  To assess everyday executive functioning, parents complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P). Three composite scores are computed for behavioral regulation, emotion regulation, and cognitive regulation, as well as a global executive composite. Higher T scores indicate poorer executive function.

  6 months post-injury

• Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P)

  To assess everyday executive functioning, parents complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P). Three composite scores are computed for behavioral regulation, emotion regulation, and cognitive regulation, as well as a global executive composite. Higher T scores indicate poorer executive function.

  12 months post-injury

• Strengths and Difficulties Questionnaire

  The Strengths and Difficulties Questionnaire (SDQ) measures psychological adjustment. Subscales include Emotional Symptoms, Conduct Problems, Hyperactivity-Inattention, Peer Problems, and Prosocial Behavior. A Total Difficulties score is also provided. Four different versions are administered based on the child's age. Higher raw scores on all scales except for Prosocial Behavior indicate more difficulties; higher raw scores on Prosocial Behavior indicate greater prosocial behavior.

  6 months post-injury

• Strengths and Difficulties Questionnaire

  The Strengths and Difficulties Questionnaire (SDQ) measures psychological adjustment. Subscales include Emotional Symptoms, Conduct Problems, Hyperactivity-Inattention, Peer Problems, and Prosocial Behavior. A Total Difficulties score is also provided. Four different versions are administered based on the child's age. Higher raw scores on all scales except for Prosocial Behavior indicate more difficulties; higher raw scores on Prosocial Behavior indicate greater prosocial behavior.

  12 months post-injury

• Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)

  Adaptive functioning is measured using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). Parents complete items designed to assess their child's ability to perform day-to-day activities in the domains of Communication, Daily Living, and Socialization. Composite scores are computed for each domain, as well as a general Adaptive Behavior Composite. Higher standard scores indicate higher adaptive functioning.

  6 months post-injury

• Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)

  Adaptive functioning is measured using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). Parents complete items designed to assess their child's ability to perform day-to-day activities in the domains of Communication, Daily Living, and Socialization. Composite scores are computed for each domain, as well as a general Adaptive Behavior Composite. Higher standard scores indicate higher adaptive functioning.

  12 months post-injury

Study Arms (2)

traumatic brain injury

Children with traumatic brain injury

orthopedic injury

Children with orthopedic injury

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Children hospitalized overnight at UPMC Children's Hospital of Pittsburgh for complicated mild to severe traumatic brain injury or orthopedic injury.

You may qualify if:

• hospitalized overnight for a non-penetrating complicated mild to severe TBI as defined by the lowest post-resuscitation Glasgow Coma Scale (GCS) score or orthopedic injury.
• Complicated mild TBI is defined as a GCS of 13-15 with neuroimaging indicating intracranial or parenchymal injury or depressed/displaced skull fracture. Moderate TBI is defined as GCS 9-12. Severe TBI is defined as GCS 3-8. Children are included in the OI group if they sustain a bone fracture, excluding to the skull or face, without any signs of head trauma or brain injury (e.g. nausea/vomiting, headache, loss of consciousness, GCS below 15 at any point).

You may not qualify if:

• non-English-speaking child or non-English-speaking parents/guardians
• documented or parent-reported history of previous TBI/concussion requiring overnight hospitalization
• pre-injury neurological disorder or intellectual disability
• pre-injury psychiatric disorder requiring hospitalization
• sensory or motor impairment precluding study measure completion
• pregnancy at the time of study participation
• participants are also excluded if at least one biosample is not able to be collected within 7 days of the injury

Sponsors & Collaborators

• University of Pittsburgh: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Publications (1)

• Treble-Barna A, Patronick J, Uchani S, Marousis NC, Zigler CK, Fink EL, Kochanek PM, Conley YP, Yeates KO. Epigenetic Effects on Pediatric Traumatic Brain Injury Recovery (EETR): An Observational, Prospective, Longitudinal Concurrent Cohort Study Protocol. Front Neurol. 2020 Jun 12;11:460. doi: 10.3389/fneur.2020.00460. eCollection 2020.

  PMID: 32595586 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, saliva, cerebrospinal fluid

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Amery Treble, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: December 4, 2019
• Study Start: July 1, 2017
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

US (1)