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Epigenetic Effects on Traumatic Brain Injury Recovery (EETR)

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ClinicalTrials.gov Identifier: NCT04186429
Recruitment Status : Recruiting
First Posted : December 4, 2019
Last Update Posted : December 4, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Amery Treble, University of Pittsburgh

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.

Condition or disease
Traumatic Brain Injury Orthopedic Injury

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.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Epigegenetic Influences on Neurobehavioral Recovery Following Pediatric Traumatic Brain Injury
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Group/Cohort
traumatic brain injury
Children with traumatic brain injury
orthopedic injury
Children with orthopedic injury



Primary Outcome Measures :
  1. NIH Toolbox Cognition Battery (NIHTB-CB) [ Time Frame: 6 months post-injury ]
    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.

  2. NIH Toolbox Cognition Battery (NIHTB-CB) [ Time Frame: 12 months post-injury ]
    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.

  3. Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P) [ Time Frame: 6 months post-injury ]
    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.

  4. Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or Preschool Version (BRIEF-P) [ Time Frame: 12 months post-injury ]
    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.

  5. Strengths and Difficulties Questionnaire [ Time Frame: 6 months post-injury ]
    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. Strengths and Difficulties Questionnaire [ Time Frame: 12 months post-injury ]
    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.

  7. Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) [ Time Frame: 6 months post-injury ]
    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.

  8. Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) [ Time Frame: 12 months post-injury ]
    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.


Biospecimen Retention:   Samples With DNA
whole blood, saliva, cerebrospinal fluid


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04186429


Contacts
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Contact: Amery Treble, PhD 412-692-6418 amery.treble-barna@pitt.edu

Locations
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United States, Pennsylvania
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Amery Treble, PhD    412-692-6418    amery.treble-barna@pitt.edu   
Principal Investigator: Amery Treble, PhD         
Sponsors and Collaborators
University of Pittsburgh
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Amery Treble, PhD University of Pittsburgh

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Responsible Party: Amery Treble, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04186429    
Other Study ID Numbers: STUDY19040402
1K01HD097030-01A1 ( U.S. NIH Grant/Contract )
First Posted: December 4, 2019    Key Record Dates
Last Update Posted: December 4, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: There is currently no IPD sharing plan in place. If the investigators choose to share IPD in the future, they will create an IPD sharing plan in consultation with the University of Pittsburgh Office of Sponsored Programs.
Keywords provided by Amery Treble, University of Pittsburgh:
traumatic brain injury
brain-derived neurotrophic factor
rehabilitation
neuropsychology
precision medicine
epigenetic
proteomic
recovery
neurobehavioral outcomes
children
childhood adversity
biomarkers
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System