Epigenetic Effects on Traumatic Brain Injury Recovery

NCT ID: NCT04186429

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 401 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2024-08-31

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.

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

traumatic brain injury

Children with traumatic brain injury

No interventions assigned to this group

orthopedic injury

Children with orthopedic injury

No interventions assigned to this group

Eligibility 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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Amery Treble

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amery Treble, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32595586 (View on PubMed)

Other Identifiers

1K01HD097030-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19040402

Identifier Type: -

Identifier Source: org_study_id