Multimodal Approach to Testing the Acute Effects of Mild Traumatic Brain Injury (mTBI)

The objective of the study is to determine the relative roles for various testing modalities in the diagnosis and prognosis of mild traumatic brain injury.

Study Overview

• Status: Completed
• Conditions: Concussion, Mild

Detailed Description

Subjects will undergo functional brain testing (magnetoencephalography, electroencephalography), anatomical brain imaging (diffusion tensor imaging, susceptibility-weighted imaging), neuropsychological testing (memory, language, processing speed), sleep patterns using actigraphy, and blood testing of candidate biomarkers. Testing will be done at 3 time points post-injury: 1 day, 14 days, and 30 days post-injury. Analysis of these tests collectively will be used to develop diagnostic tools for acute mTBI.

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• United States
  • California
    • Pasadena, California, United States, 91105
      • HMRI
    • Pasadena, California, United States, 91101
      • Huntington Medical Research Institutes
    • Pasadena, California, United States, 91105
      • Molecular Neurology Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study participants (control, mTBI) will be referred by the Huntington Hospital Emergency Department staff. ED staff will determine the eligibility criteria. If consent is achieved, testing will occur at pre-determined times: 1 day, 14 days, and 30 days post-injury.

Description

Inclusion Criteria:

1. Civilian (non-military) presenting to HMH ED.

Exclusion Criteria:

1. Prior history of diagnosed TBI.
2. Other significant non-head injury/trauma or open wound.
3. Other significant medical co-morbidities, such as heart disease or cancer.
4. Self-reported current use or substances contributing to ED visit (e.g. illicit drugs, medications, alcohol abuse).
5. Currently diagnosed psychological condition (e.g. depression, PTSD).
6. Medications for psychological or neurological disorder.
7. Any implanted metal, such as medical device or braces on teeth.
8. Injury to the back or other injury that will make it difficult for the participant to tolerate tests.
9. Injury to dominant arm that would cause difficulty using computer or responding to stimuli during functional imaging.
10. Pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Mild traumatic brain injury (mTBI); Patients admitted to Huntington Memorial Hospital (HMH), Pasadena CA, Emergency Department (ED) diagnosed with mTBI by history (alteration of consciousness, post-traumatic amnesia, loss of consciousness) and normal brain computed tomography (CT).
Control; Patients admitted to HMH ED for minor extremity trauma (sprains) and no evidence of mTBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in objective measures of brain function (MEG/EEG, blood biomarkers)	For MEG/EEG, resting state analyses of brain function will be conducted to include frequency band analyses localizing, for example, delta slow wave activity, and establishing functional connectivity scores at three time points post injury (day 1, day 14, day 30). For blood biomarkers, serum levels in approximately ten biomarkers will be measured to determine amount in each and if changes occur at three time points post-injury.	Day 1, day 14, and day 30 post-injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in anatomical measures of brain function (DTI, SWI)	Diffusion Tensor-derived measures will be calculated for control and mTBI participants to determine if changes occur at three time points post-injury (day 1, day 14, day 30).	Day 1, day 14, and day 30 post-injury

Collaborators and Investigators

• Sponsor: Huntington Medical Research Institutes
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Michael G Harrington, MB, Huntington Medical Research Institutes

Publications and helpful links

General Publications

• Bigler ED. Neuropsychology and clinical neuroscience of persistent post-concussive syndrome. J Int Neuropsychol Soc. 2008 Jan;14(1):1-22. doi: 10.1017/S135561770808017X.
• Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008 Jan 31;358(5):453-63. doi: 10.1056/NEJMoa072972. Epub 2008 Jan 30.
• Huang MX, Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J, Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D, Coimbra R, Lee RR. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.
• Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S, Orrison WW. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55. doi: 10.1097/01.HTR.0000271115.29954.27.
• Pelinka LE, Kroepfl A, Schmidhammer R, Krenn M, Buchinger W, Redl H, Raabe A. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma. 2004 Nov;57(5):1006-12. doi: 10.1097/01.ta.0000108998.48026.c3.
• Vos PE, Lamers KJ, Hendriks JC, van Haaren M, Beems T, Zimmerman C, van Geel W, de Reus H, Biert J, Verbeek MM. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology. 2004 Apr 27;62(8):1303-10. doi: 10.1212/01.wnl.0000120550.00643.dc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: February 18, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 24, 2014

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: November 6, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: MRI; biomarkers; mTBI; EEG; MEG; Blood; DTI; concussion; Mild traumatic injury to extremity (for controls)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: 27294/1; W81XWH-13-1-0005 (Other Grant/Funding Number: USAMRMC)