Traumatic Brain InjuryEETRNCT04186429
Epigenetic Effects on Traumatic Brain Injury Recovery
An observational study of Traumatic Brain Injury and Orthopedic Injury, run by University of Pittsburgh at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Traumatic Brain Injury, Orthopedic Injury
- How many people
- 401 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2017to 31 Aug 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 18 years
- All sexes
- Child, Adult
Study population: Children hospitalized overnight at UPMC Children's Hospital of Pittsburgh for complicated mild to severe traumatic brain injury or orthopedic injury.
Who may be able to join
- -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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
About this study
Official title: Epigegenetic Influences on Neurobehavioral Recovery Following Pediatric Traumatic Brain Injury
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.
Read the 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.
- 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
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| traumatic brain injury | Children with traumatic brain injury | |
| orthopedic injury | Children with orthopedic injury |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 months post-injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2019
- Study start1 Jul 2017
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 401 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Amery Treble, University of Pittsburgh
- Investigators
- Amery Treble, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04186429
- Sponsor's protocol ID
- STUDY19040402
- Other IDs
- 1K01HD097030-01A1
- Acronym
- EETR
- Status last verified
- Sep 2024
- First submitted
- 26 Nov 2019
- Last updated
- 19 Sep 2024
- Results posted
- No
- Individual data sharing
- Undecided: 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.
Publications
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.
PubMed 32595586
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigegenetic Influences on Neurobehavioral Recovery Following Pediatric Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT04186429
- Acronym / sponsor ID
- EETR / STUDY19040402
- Conditions
- Traumatic Brain Injury, Orthopedic Injury
- Keywords
- traumatic brain injury, rehabilitation, neuropsychology, precision medicine, epigenetic, proteomic, brain-derived neurotrophic factor, recovery
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 401 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 4 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| traumatic brain injury | – | –Children with traumatic brain injury |
| orthopedic injury | – | –Children with orthopedic injury |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- Children hospitalized overnight at UPMC Children's Hospital of Pittsburgh for complicated mild to severe traumatic brain injury or orthopedic injury.
Key inclusion criteria (2 listed)
- -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).
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 32595586Treble-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.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amery Treble, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury and Orthopedic Injury, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NIH Toolbox Cognition Battery (NIHTB-CB) (time frame: 6 months post-injury). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04186429, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.