Clinical trial NCT02706574: Brain Injury Assessment Study at Hennepin County Medical Center
Official title: Brain Injury Assessment Study at Hennepin County Medical Center
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Traumatic Brain Injury
Keywords: Eye Tracking
Blood-based Biomarkers
CSF-based Biomarkers
Magnetic Resonance Imaging
Computed Tomography Scan
Outcome Measures
Lead sponsor: CentraCare
Sponsor class: OTHER
Collaborators: name: Abbott Diagnostics Division
First posted: 2016-03-11
Enrollment: 774
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will include all trauma patients that present to the HCMC Emergency Department, trauma bay or as a direct transfer to neurosurgery.

Brief summary: The goals of this study are to develop an objective, multi-modal classification scheme and outcome measures for traumatic brain injury based on several measures: (1) blood-based biomarkers (indicates which cell types are damaged), (2) eye tracking (detects mass effect/elevated intracranial pressure and pathway disruption), (3) radiographic measures of CT and MRI (detect structural abnormalities), and (4) standardized outcome assessments.

Detailed description: Background:

Current algorithms for assessment of the severity of brain injury include Glasgow Coma Scale score and other measures. These measures are adequate for relating acute severity but are insufficiently sensitive for subtle pathology which can result in persistent deficit. The Glasgow Coma Scale (GCS) and other measures also do not enable differentiation among types of injury. Thus patients grouped into a single GCS level entering a clinical trial may have vastly heterogeneous severity and type of injury. Because outcomes also vary accordingly, inappropriate classification undermines the integrity of a clinical trial. Improved classification of injury will enable more precise delineation of disease severity and type for patients with a traumatic brain injury (TBI) in clinical trials.

Additionally, current brain injury trials rely on outcome measures such as Glasgow Outcome Scale Extended, which capture global phenomena but fail to assess for subtle differences in outcome. Thus, many recent trials for brain injury therapeutics have failed. Sensitive outcome measures are needed to determine how well patients have recovered from brain injury in order to test therapeutics and prophylactics.

Overview of Methods:

All trauma patients that span the full spectrum ranging from non-brain injured, to CT-negative, to structurally brain injured, requiring surgery will be included in this study. A total of 1000 patients and 200 controls will be recruited over approximately 2 years.

The study has been approved by the Institutional Review Board (IRB), enabling a waiver of consent for all trauma patients until it becomes appropriate to obtain consent. The trauma patients will be screened upon admission, and potentially during the period of waived consent, for participation in the study (target N for screening = 16,000 per year). The screening process will include:

1. A standardized history and physical examination done as a part of the standard of care.
2. A standardized assessment to be done by research personnel.
3. Eye tracking.
4. Analysis of serum biomarkers at three time points within the first 24 hours.
5. MRI scans for a subset of patients within one week of their injury.
6. CT scans as clinically indicated.
7. Pathologic specimen as clinically indicated.
8. Cerebrospinal fluid (CSF) analysis in patients that receive a ventriculostomy catheter.
9. Brain tissue oxygenation analysis in patients receiving Licox.

The screening process that takes place, potentially during the period of waived consent, will allow for patients to be stratified into the following groups with the associated targeted sample sizes over two years:

1. Isolated TBI (N=400)
2. Combined TBI and Body Trauma (N=400)
3. Isolated Body Trauma (N=200)
4. Healthy, Uninjured Controls (N=200)

Upon discharge, patients will be recruited to enroll in a long-term follow-up assessment. They will be seen in the hospital at the following time points post-injury: 2 weeks, 4 weeks, 3 months, 6 months, and 1 year. At these follow-up visits, participants will be asked to undergo various assessments depending on the follow-up visit, including:

1. Eye Tracking.
2. Blood draw for blood-based biomarker analysis.
3. MRI scan if they had one within one week post-injury.
4. CT scan if they had one at admission.
5. Cognitive, Neurologic, and Quality of Life Assessments

Data Analysis:

Patient outcomes, measured with sensitive outcome measures, will be linked to acute research findings in order to create a classification scheme for brain injury that is based on objective measures and can accurately predict prognosis.

Eligibility criteria: Inclusion Criteria:

* All trauma patients that present to Hennepin County Medical Center.

Exclusion Criteria:

* Age \> 4 years old;
* Major psychiatric or neurologic disorder: Active Psychotic Break, Trauma due to Suicide Attempt, Epilepsy, Multiple Sclerosis, Dementia, Guillain Barre Syndrome/Chronic Inflammatory Demyelinating Polyneuropathy, Significant Neurodegenerative Disorders, Muscular Dystrophy, and/or Malignant Intracranial Mass with Significant Mass Effect.
* Developmentally Abnormal, or
* Prisoners.

Primary outcomes:
measure: Change in Metrics of Eye Movements during Recovery as Measured by Eye Tracking
timeFrame: Post-Injury Time Points of Data Collection: 2 weeks, 4 weeks, 3 months, 6 months, and 1 year.
measure: Change in Proteomic Concentrations of Blood-Based Biomarkers during Recovery as Measured by Blood Draws
timeFrame: Post-Injury Time Points of Data Collection: 2 weeks, 4 weeks, 3 months, 6 months, and 1 year.
measure: Change in Observable Neural Abnormalities as measured by Magnetic Resonance Imaging
timeFrame: Post-Injury Time Points of Data Collection: within 1 week and at 1 year.
measure: Computed Tomography Scan
timeFrame: Post-Injury Time Point of Data Collection: 1 year.
Secondary outcomes:
measure: Change in Neurological Examination during Recovery as Measured by the Neurological Outcome Scale after Traumatic Brain Injury
timeFrame: Post-Injury Time Points of Data Collection: 2 weeks, 4 weeks, 3 months, 6 months, and 1 year.
measure: Change in Cognitive Function and Symptom Severity during Recovery as Measured with the Sports Concussion Assessment Tool 3 (SCAT3)
timeFrame: Post-Injury Time Points of Data Collection: 2 weeks, 4 weeks, 3 months, 6 months, and 1 year.
measure: Change in Quality of Life during Recovery as Measured with the Mayo-Portland Adaptability Inventory-4 (MPAI-4)
timeFrame: Post-Injury Time Points of Data Collection: 3 months, and 1 year.
measure: Change in Global Outcome during Recovery as Measured with the Glasgow Outcome Scale-Extended (GOS-E)
timeFrame: Post-Injury Time Points of Data Collection: 3 months, 6 months, and 1 year.
measure: Change in Memory Performance during Recovery as Measured with the Galveston Orientation and Amnesia Test (GOAT)
timeFrame: Post-Injury Time Points of Data Collection: 3 months and 1 year.
measure: The Number of Prior Brain Injuries the Patient has Suffered as Measured with the Boston Assessment of Traumatic Brain Injury-Lifetime
timeFrame: Post-Injury Time Point of Data Collection: 2 weeks.
measure: Change in Cognitive Functioning during Recovery as Measured by the Brief Test of Adult Cognition by Telephone
timeFrame: Post-Injury Time Points of Data Collection: 3 months and 1 year.
Other outcomes:
Locations:
Study officials:
affiliation: Physician, Neurosurgery
name: Uzma Samadani, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Samadani U. A new tool for monitoring brain function: eye tracking goes beyond assessing attention to measuring central nervous system physiology. Neural Regen Res. 2015 Aug;10(8):1231-3. doi: 10.4103/1673-5374.162752. No abstract available.
citation: Samadani U, Ritlop R, Reyes M, Nehrbass E, Li M, Lamm E, Schneider J, Shimunov D, Sava M, Kolecki R, Burris P, Altomare L, Mehmood T, Smith T, Huang JH, McStay C, Todd SR, Qian M, Kondziolka D, Wall S, Huang P. Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion. J Neurotrauma. 2015 Apr 15;32(8):548-56. doi: 10.1089/neu.2014.3687. Epub 2015 Feb 6.
citation: Samadani U, Farooq S, Ritlop R, Warren F, Reyes M, Lamm E, Alex A, Nehrbass E, Kolecki R, Jureller M, Schneider J, Chen A, Shi C, Mendhiratta N, Huang JH, Qian M, Kwak R, Mikheev A, Rusinek H, George A, Fergus R, Kondziolka D, Huang PP, Smith RT. Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip. J Neurosurg. 2015 Mar;122(3):707-20. doi: 10.3171/2014.10.JNS14762. Epub 2014 Dec 12.