Brain InjuriesNCT02688660
MRI Markers of Outcome After Severe Pediatric TBI
An observational study of Brain Injuries, run by University of Wisconsin, Madison at 21 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 0 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Injuries
- What is being tested?
- MRI Scans
- How many people
- 82 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 1 Apr 2016to May 2022
- 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 0 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Pediatric patients who have experienced TBI and had an acute MRI scan and those who participate in the prospective phase and obtain a follow-up MRI. Healthy controls will also be enrolled.
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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.).
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
United States18 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342
Johns Hopkins University
Baltimore, Maryland, 21218
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033
University of Tennessee
Knoxville, Tennessee, 37996
American Family Children's Hospital (AFCH)
Madison, Wisconsin, 53792
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Virginia Commonwealth University
Richmond, Virginia, 23284
University of Utah Primary Children's Medical Center
Salt Lake City, Utah, 84108
UC San Diego Health Sciences Center
San Diego, California, 92103
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20009
United Kingdom2 sites
Birmingham Children's Hospital
Birmingham, England, B4 6NH
University Hospital Southampton
Southampton, Hampshire, SO16 6YD
About this study
Official title: MRI Markers of Outcome After Severe Pediatric Traumatic Brain Injury (TBI)
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.
Read the detailed 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.
- Conditions
- Brain Injuries
- Being tested
- MRI Scans
- Keywords
- Pediatrics, Neuroimaging
- Medical subject headings
- Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI ScansOther
| Study group | Role | What they receive |
|---|---|---|
| ADAPT Study Population | This cohort will be subjects from the ADAPT study who had an acute MRI scan which has been uploaded into the ADAPT database from all participating sites. | |
| Follow-Up MRI | This cohort will include patients from ADAPT sites who choose to participate in this option and obtain a follow-up MRI approximately 1 year after the TBI. Receives: Other: MRI Scans | |
| Healthy Controls | This cohort will have one MRI to be used in comparison of the above cohorts. Receives: Other: MRI Scans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Atrophy
Global and regional cerebral atrophy will be assessed using MRI
Measured: 1 year
White matter fractional anisotropy
Fractional Anisotropy will be assessed using Diffusion Tensor MRI
Measured: 1 year
Brain network connectivity
Network connectivity will be assessed using resting-state functional MRI
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2016 (estimated)
- Study start1 Apr 2016
- Primary completionMay 2022
- Study completionMay 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Other
- Time perspective
- Other
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Peter Ferrazzano, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02688660
- Sponsor's protocol ID
- 2015-0185
- Other IDs
- R01NS092870, A536700, PEDIATRICS-GEN, Protocol Version 8/28/2019
- Status last verified
- Apr 2022
- First submitted
- 29 Jan 2016
- Last updated
- 24 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 23876117Tasker 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.
PubMed 20829579Birn 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.
PubMed 24863147Yue 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.
PubMed 23815563Beers 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.
PubMed 22220819McCauley 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.
PubMed 21644810Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007 Jul;4(3):316-29. doi: 10.1016/j.nurt.2007.05.011.
PubMed 17599699
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MRI Markers of Outcome After Severe Pediatric Traumatic Brain Injury (TBI)
- ClinicalTrials.gov ID
- NCT02688660
- Acronym / sponsor ID
- 2015-0185
- Conditions
- Brain Injuries
- Keywords
- Pediatrics, Neuroimaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- May 2022 (actual)
- Study completion
- May 2022 (actual)
- First posted
- 23 Feb 2016 (estimated)
- 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.
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.
Detailed 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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ADAPT Study Population | – | –This cohort will be subjects from the ADAPT study who had an acute MRI scan which has been uploaded into the ADAPT database from all participating sites. |
| Follow-Up MRI | – | Other: MRI ScansThis cohort will include patients from ADAPT sites who choose to participate in this option and obtain a follow-up MRI approximately 1 year after the TBI. |
| Healthy Controls | – | Other: MRI ScansThis cohort will have one MRI to be used in comparison of the above cohorts. |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Pediatric patients who have experienced TBI and had an acute MRI scan and those who participate in the prospective phase and obtain a follow-up MRI. Healthy controls will also be enrolled.
Key inclusion criteria (9 listed)
- 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
- Children 9 through < 18 years of age with severe TBI
- Consent for a follow-up MRI within 10 years of the time of TBI
Key exclusion criteria (5 listed)
- TBI \& controls:
- Anyone unable to tolerate a non-sedated MRI
- Any history of head injury resulting in loss of consciousness
- Standard contraindications to MRI (metallic implants, implanted electronic devices, pregnancy, etc.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI Scans | Other | Follow-Up MRI, Healthy Controls |
Primary outcome
Cerebral Atrophy
Time frame: 1 year
Global and regional cerebral atrophy will be assessed using MRI
White matter fractional anisotropy
Time frame: 1 year
Fractional Anisotropy will be assessed using Diffusion Tensor MRI
Brain network connectivity
Time frame: 1 year
Network connectivity will be assessed using resting-state functional MRI
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 24 Jun 2022.
- Background: PubMed 23876117Bigler 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.
- Background: PubMed 20829579Tasker 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.
- Background: PubMed 24863147Birn 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.
- Background: PubMed 23815563Yue 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.
- Background: PubMed 22220819Beers 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.
- Background: PubMed 21644810McCauley 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.
- Background: PubMed 17599699Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007 Jul;4(3):316-29. doi: 10.1016/j.nurt.2007.05.011.
- Individual participant dataSharing planned: Yes
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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.
Peter Ferrazzano, MD principal investigator
University of Wisconsin, Madison
21 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Injuries, run by University of Wisconsin, Madison at 21 sites in 3 countries.
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 9 inclusion and 5 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 24 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, United Kingdom, Australia. 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?
Cerebral Atrophy (time frame: 1 year). The study lists 3 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 NCT02688660, which also lists 7 linked publications.
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 24 Jun 2022.