- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04186429
Epigenetic Effects on Traumatic Brain Injury Recovery (EETR)
Epigegenetic Influences on Neurobehavioral Recovery Following Pediatric Traumatic Brain Injury
Study Overview
Status
Conditions
Detailed Description
Unexplained heterogeneity in outcomes following pediatric traumatic brain injury (TBI) is one of the most critical barriers to the development of effective prognostic tools and therapeutics. The addition of personal biological factors to our prediction models may account for a significant portion of unexplained variance and advance the field towards precision rehabilitation medicine. The overarching goal of the Epigenetic Effects on Pediatric Traumatic Brain Injury Recovery (EETR) study is to investigate an epigenetic biomarker involved in both childhood adversity and post-injury neuroplasticity to better understand heterogeneity in neurobehavioral outcomes following pediatric TBI. The primary hypothesis is that childhood adversity will be associated with poorer neurobehavioral recovery in part through an epigenetically mediated reduction in brain-derived neurotrophic factor (BDNF) expression in response to TBI.
EETR is an observational, prospective, longitudinal concurrent cohort study of children aged 3-18 years with either TBI (n=200) or orthopedic injury (n=100), recruited from the UPMC Children's Hospital of Pittsburgh. Participants complete study visits acutely and at 6- and 12-months post-injury. Blood and saliva biosamples are collected at all time points-and CSF when available acutely-for epigenetic and proteomic analysis of BDNF. Additional measures assess injury characteristics, pre- and post-injury child neurobehavioral functioning, childhood adversity, and potential covariates/confounders. Analyses will characterize BDNF DNA methylation and protein levels over the recovery period and investigate this novel biomarker as a potential biological mechanism underlying the known association between childhood adversity and poorer neurobehavioral outcomes following pediatric TBI.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Amery Treble, PhD
- Phone Number: 412-692-6418
- Email: amery.treble-barna@pitt.edu
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224
- Recruiting
- UPMC Children's Hospital of Pittsburgh
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Contact:
- Amery Treble, PhD
- Phone Number: 412-692-6418
- Email: amery.treble-barna@pitt.edu
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Principal Investigator:
- Amery Treble, PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion criteria:
-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).
Exclusion criteria:
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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traumatic brain injury
Children with traumatic brain injury
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orthopedic injury
Children with orthopedic injury
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
NIH Toolbox Cognition Battery (NIHTB-CB)
Time Frame: 6 months post-injury
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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.
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6 months post-injury
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NIH Toolbox Cognition Battery (NIHTB-CB)
Time Frame: 12 months post-injury
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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.
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12 months post-injury
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Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P)
Time Frame: 6 months post-injury
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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.
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6 months post-injury
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Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P)
Time Frame: 12 months post-injury
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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.
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12 months post-injury
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Strengths and Difficulties Questionnaire
Time Frame: 6 months post-injury
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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.
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6 months post-injury
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Strengths and Difficulties Questionnaire
Time Frame: 12 months post-injury
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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.
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12 months post-injury
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Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
Time Frame: 6 months post-injury
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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.
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6 months post-injury
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Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
Time Frame: 12 months post-injury
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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.
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12 months post-injury
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Amery Treble, PhD, University of Pittsburgh
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY19040402
- 1K01HD097030-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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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