MRI Markers of Outcome After Severe Pediatric TBI

Brain Injuries Clinical Trial

Official title:

MRI Markers of Outcome After Severe Pediatric Traumatic Brain Injury (TBI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02688660
• Other study ID #: 2015-0185
• Secondary ID: R01NS092870A5367
• Status: Completed
• Start date: April 1, 2016
• Est. completion date: May 2022

Study information

• Verified date: April 2022
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Traumatic brain injury (TBI) is the leading cause of death or disability in children. Each year in the United States, pediatric TBI results in an estimated 630,000 emergency room visits, 58,900 hospitalizations, and 7000 deaths. The incidence of long-term disability after severe TBI is high, with over 60% of children requiring educational or community based supportive services 12 months post-injury. Over 5,000 children require inpatient rehabilitation after TBI each year and an estimated 145,000 US children are currently living with disabilities after a severe TBI. Hospital costs for the acute treatment of children with TBI are estimated at ~$2.6 billion each year, while the gross annual costs accounting for long-term care and lost productivity approach $60 billion. Therefore, pediatric TBI is a major public health concern and new ways to diagnose and treat TBI are urgently needed.

Description:

Severe pediatric TBI results in a range of neurocognitive and behavioral deficits with resultant impact on school performance, social functioning, and quality of life. Sixty percent of children suffer from long-term functional impairments after severe TBI, and more than 40% demonstrate deficits in multiple cognitive and psychological domains. Importantly, a recent meta-analysis revealed that rather than catching up to their peers in these domains, children with severe TBI fall further behind over time. These deficits in cognitive and emotional function have a major impact on the child's quality of life after a TBI. A large study recently reported that severe TBI patients demonstrated lower quality of life than children undergoing active treatment for cancer. Considerable variation exists in the severity of impairment within each cognitive domain from patient to patient, likely relating to the mechanism of injury, the type and location of lesion, patient age, and pre-morbid functioning among other factors. While clinical scales such as the Glasgow Coma Scale (GCS) are useful for assessing injury severity and may provide general prognostic information, they are insufficient to identify risk for specific cognitive deficits. Identifying predictors of impairment within specific domains would aid in directing rehabilitation strategies towards at-risk cognitive domains, thereby improving long-term function and quality of life.

The investigators are partnering with an ongoing pediatric TBI trial (ADAPT Trial: Approaches and Decisions in Acute Pediatric TBI) and will also be enrolling past UW patients and healthy controls. Consistency in timing of follow-up scans, large sample size and access to the ADAPT Trial injury severity data and neuropsychological testing will give this study unprecedented power to assess the relationship between early MRI findings and subsequent atrophy, white matter injury, network connectivity changes and neurocognitive and behavioral impairments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: May 2022
• Est. primary completion date: May 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

Aim 1 Subjects:

• Children 0 through < 18 years of age

• Diagnosis of severe TBI (defined as a Glasgow Coma Scale (GCS) score less than or equal to 8)

• Had an intracranial pressure (ICP) monitor as part of standard care

Aims 2 & 3 Subjects:

• Children 9 through < 18 years of age with severe TBI

• Consent for a follow-up MRI within 10 years of the time of TBI

Controls:

• Healthy children greater than or equal to 9 and < 18 years of age.

Exclusion Criteria:

• TBI & controls:

• Anyone unable to tolerate a non-sedated MRI

Controls:

• Any history of head injury resulting in loss of consciousness

• Standard contraindications to MRI (metallic implants, implanted electronic devices, pregnancy, etc.).

Related Conditions & MeSH terms

• Brain Injuries

Intervention

Other:
• MRI Scans

Locations

Country	Name	City	State
Australia	The Royal Children's Hospital	Melbourne	Victoria
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	University Hospital Southampton	Southampton	Hampshire
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	University of Tennessee	Knoxville	Tennessee
United States	American Family Children's Hospital (AFCH)	Madison	Wisconsin
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah Primary Children's Medical Center	Salt Lake City	Utah
United States	UC San Diego Health Sciences Center	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Australia,  United Kingdom, 

References & Publications (7)

Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007 Jul;4(3):316-29. Review. — View Citation

Beers SR, Wisniewski SR, Garcia-Filion P, Tian Y, Hahner T, Berger RP, Bell MJ, Adelson PD. Validity of a pediatric version of the Glasgow Outcome Scale-Extended. J Neurotrauma. 2012 Apr 10;29(6):1126-39. doi: 10.1089/neu.2011.2272. Epub 2012 Apr 10. — View Citation

Bigler ED, Abildskov TJ, Petrie J, Farrer TJ, Dennis M, Simic N, Taylor HG, Rubin KH, Vannatta K, Gerhardt CA, Stancin T, Owen Yeates K. Heterogeneity of brain lesions in pediatric traumatic brain injury. Neuropsychology. 2013 Jul;27(4):438-51. doi: 10.1037/a0032837. — View Citation

Birn RM, Shackman AJ, Oler JA, Williams LE, McFarlin DR, Rogers GM, Shelton SE, Alexander AL, Pine DS, Slattery MJ, Davidson RJ, Fox AS, Kalin NH. Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety. Mol Psychiatry. 2014 Aug;19(8):915-22. doi: 10.1038/mp.2014.46. Epub 2014 May 27. — View Citation

McCauley SR, Wilde EA, Anderson VA, Bedell G, Beers SR, Campbell TF, Chapman SB, Ewing-Cobbs L, Gerring JP, Gioia GA, Levin HS, Michaud LJ, Prasad MR, Swaine BR, Turkstra LS, Wade SL, Yeates KO; Pediatric TBI Outcomes Workgroup. Recommendations for the use of common outcome measures in pediatric traumatic brain injury research. J Neurotrauma. 2012 Mar 1;29(4):678-705. doi: 10.1089/neu.2011.1838. Epub 2011 Aug 24. — View Citation

Tasker RC, Westland AG, White DK, Williams GB. Corpus callosum and inferior forebrain white matter microstructure are related to functional outcome from raised intracranial pressure in child traumatic brain injury. Dev Neurosci. 2010;32(5-6):374-84. doi: 10.1159/000316806. Epub 2010 Sep 8. — View Citation

Yue JK, Vassar MJ, Lingsma HF, Cooper SR, Okonkwo DO, Valadka AB, Gordon WA, Maas AI, Mukherjee P, Yuh EL, Puccio AM, Schnyer DM, Manley GT; TRACK-TBI Investigators. Transforming research and clinical knowledge in traumatic brain injury pilot: multicenter implementation of the common data elements for traumatic brain injury. J Neurotrauma. 2013 Nov 15;30(22):1831-44. doi: 10.1089/neu.2013.2970. Epub 2013 Sep 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebral Atrophy	Global and regional cerebral atrophy will be assessed using MRI	1 year
Primary	White matter fractional anisotropy	Fractional Anisotropy will be assessed using Diffusion Tensor MRI	1 year
Primary	Brain network connectivity	Network connectivity will be assessed using resting-state functional MRI	1 year