Cerebral Autoregulation, Brain Perfusion, and Neurocognitive Outcomes After Traumatic Brain Injury

NCT06480838 | Recruiting

• 2 other identifiers: STU-2023-02541R01NS129934-01A1
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 3

Brief Summary

Cognitive impairment after moderate to severe traumatic brain injury (msTBI) not only significantly affects the quality of life in individuals with msTBI, but also increases the possibility of late-life dementia. The goal of this study is to determine whether acute (\< 1 week) cerebrovascular injury and its recovery within the first year postinjury measured by cerebral autoregulation and brain perfusion are associated with cognitive outcome at 12 months after msTBI. The results from this study will improve our understanding of cerebrovascular contributions to cognitive decline related to TBI and provide critical data to inform the development of strategies based on vascular mechanisms to improve cognition and prevent neurodegeneration after msTBI.

Conditions

Traumatic Brain Injury With Loss of Consciousness; Brain Injury Traumatic Severe; Brain Injury Traumatic Moderate; TBI (Traumatic Brain Injury); TBI

Outcome Measures

Primary Outcomes (1)

• NIH Toolbox Cognitive Battery

  NIH Toolbox is a set of brief, comprehensive assessment tools. This study protocol will use the Cognitive battery of the Toolbox consisting of 7 subtests designed to measure executive function and attention (Flanker and Dimensional Change Card Sort), episodic memory (Picture Sequence Memory Test), working memory (List Sorting Working Memory Test), processing speed (Pattern Comparison Processing Speed and Flanker), and language (Picture Vocabulary Test). Assessments will be administered on an iPad (5th generation).

  September 1, 2023 - May 31, 2028

Secondary Outcomes (10)

• Hopkins Verbal Learning Test-Revised (HVLT-R)

  September 1, 2023 - May 31, 2028

• Trail Making Test A &B (TMT A & B)

  September 1, 2023 - May 31, 2028

• Wechsler Adult Intelligence Scale (WAIS) IV Processing Speed Index (Coding and Symbol Search subtests)

  September 1, 2023 - May 31, 2028

• Revised-Glasgow Outcome Scale-Extended (R-GOSE)

  September 1, 2023 - May 31, 2028

• Expanded Disability Rating Scale Post-Acute Interview (E-DRS-PI)

  September 1, 2023 - May 31, 2028

Study Arms (2)

msTBI

Subjects with moderate to severe TBI within the first week after initial injury

Orthopedic control

Orthopedic trauma controls within the first week after initial injury

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with either moderate to severe traumatic brain injury within one week of injury, or plain orthopedic trauma within one week of injury.

You may qualify if:

• Documented/Verified TBI (ACRM Criteria) (eg, motor vehicle (MV) occupant, MV pedestrian/cyclist, fall, other non-intentional, violence/assault)
• A documented moderate to severe TBI defined as: Glasgow Coma Scale (GCS) \< 13, or loss of consciousness (LOC) \> 30 minutes, or posttraumatic amnesia (PTA) \> 24 hours or intracranial neuroimaging abnormalities
• Between the age 18 - 80 year-old
• ≤ 1 week postinjury
• Acute brain CT for clinical care
• Admitted to the hospital for TBI
• Visual acuity/hearing adequate for testing
• Fluent in English or Spanish
• Patient or LAR ability to provide informed consent

You may not qualify if:

• Age greater or less than the range 18-80 years
• Significant polytrauma that would interfere with follow-up and outcome assessment
• Major debilitating baseline mental health disorders (e.g., schizophrenia, bipolar disorder, severe depression with active suicidal thoughts at the time of evaluation) that would interfere with follow-up and the validity of outcome assessment.
• Major debilitating neurological disease (e.g., stroke, CVA, dementia, tumor) impairing baseline awareness, cognition, or validity of follow-up and outcome assessment.
• Significant history of pre-existing conditions that would interfere with follow-up and outcome assessment (e.g., active substance abuse, alcoholism, HIV/AIDs, end-stage cancers, learning disabilities, developmental disorders)
• Patients on psychiatric hold
• Prisoners or patients in custody
• Pregnancy in female subjects
• Low likelihood of follow-up (e.g., participants or family indicating low interest, residence in another state or country, homeless or lack of reliable contacts)
• Current participant in an interventional trial (e.g., drug, device, behavioral)
• Penetrating TBI
• Spinal cord injury with ASIA score of C or worse
• Contraindications to MRI

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Albert Einstein College of Medicine: collaborator
• Texas Health Resources: collaborator
• Institute for Exercise and Environmental Medicine: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (3)

Texas Health Presbyterian Hospital

Dallas, Texas, 75231, United States

RECRUITING

Parkland Health and Hospital System

Dallas, Texas, 75235, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Related Publications (26)

• Miller GF, DePadilla L, Xu L. Costs of Nonfatal Traumatic Brain Injury in the United States, 2016. Med Care. 2021 May 1;59(5):451-455. doi: 10.1097/MLR.0000000000001511.

  PMID: 33528230 BACKGROUND

• Wilson L, Stewart W, Dams-O'Connor K, Diaz-Arrastia R, Horton L, Menon DK, Polinder S. The chronic and evolving neurological consequences of traumatic brain injury. Lancet Neurol. 2017 Oct;16(10):813-825. doi: 10.1016/S1474-4422(17)30279-X. Epub 2017 Sep 12.

  PMID: 28920887 BACKGROUND

• Dikmen SS, Corrigan JD, Levin HS, Machamer J, Stiers W, Weisskopf MG. Cognitive outcome following traumatic brain injury. J Head Trauma Rehabil. 2009 Nov-Dec;24(6):430-8. doi: 10.1097/HTR.0b013e3181c133e9.

  PMID: 19940676 BACKGROUND

• Ponsford JL, Olver JH, Curran C. A profile of outcome: 2 years after traumatic brain injury. Brain Inj. 1995 Jan;9(1):1-10. doi: 10.3109/02699059509004565.

  PMID: 7874089 BACKGROUND

• Julie Schneider SJ, Jordan T. Gladman, Roderick A. Corriveau. ADRD Summit 2019 Report to the National Advisory Neurological Disorders and Stroke Council. 2019;

  BACKGROUND

• Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C, Fox N, Gitlin LN, Howard R, Kales HC, Larson EB, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N. Dementia prevention, intervention, and care. Lancet. 2017 Dec 16;390(10113):2673-2734. doi: 10.1016/S0140-6736(17)31363-6. Epub 2017 Jul 20. No abstract available.

  PMID: 28735855 BACKGROUND

• Nordstrom P, Michaelsson K, Gustafson Y, Nordstrom A. Traumatic brain injury and young onset dementia: a nationwide cohort study. Ann Neurol. 2014 Mar;75(3):374-81. doi: 10.1002/ana.24101.

  PMID: 24812697 BACKGROUND

• Gardner RC, Burke JF, Nettiksimmons J, Kaup A, Barnes DE, Yaffe K. Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity. JAMA Neurol. 2014 Dec;71(12):1490-7. doi: 10.1001/jamaneurol.2014.2668.

  PMID: 25347255 BACKGROUND

• Ramos-Cejudo J, Wisniewski T, Marmar C, Zetterberg H, Blennow K, de Leon MJ, Fossati S. Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link. EBioMedicine. 2018 Feb;28:21-30. doi: 10.1016/j.ebiom.2018.01.021. Epub 2018 Jan 31.

  PMID: 29396300 BACKGROUND

• Preiksaitis A, Krakauskaite S, Petkus V, Rocka S, Chomskis R, Dagi TF, Ragauskas A. Association of Severe Traumatic Brain Injury Patient Outcomes With Duration of Cerebrovascular Autoregulation Impairment Events. Neurosurgery. 2016 Jul;79(1):75-82. doi: 10.1227/NEU.0000000000001192.

  PMID: 26695090 BACKGROUND

• Vavilala MS, Muangman S, Tontisirin N, Fisk D, Roscigno C, Mitchell P, Kirkness C, Zimmerman JJ, Chesnut R, Lam AM. Impaired cerebral autoregulation and 6-month outcome in children with severe traumatic brain injury: preliminary findings. Dev Neurosci. 2006;28(4-5):348-53. doi: 10.1159/000094161.

  PMID: 16943658 BACKGROUND

• Sviri GE, Aaslid R, Douville CM, Moore A, Newell DW. Time course for autoregulation recovery following severe traumatic brain injury. J Neurosurg. 2009 Oct;111(4):695-700. doi: 10.3171/2008.10.17686.

  PMID: 19392589 BACKGROUND

• Thomas BP, Tarumi T, Wang C, Zhu DC, Tomoto T, Munro Cullum C, Dieppa M, Diaz-Arrastia R, Bell K, Madden C, Zhang R, Ding K. Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury. Brain Res. 2021 Nov 15;1771:147631. doi: 10.1016/j.brainres.2021.147631. Epub 2021 Aug 28.

  PMID: 34464600 BACKGROUND

• Amyot F, Kenney K, Spessert E, Moore C, Haber M, Silverman E, Gandjbakhche A, Diaz-Arrastia R. Assessment of cerebrovascular dysfunction after traumatic brain injury with fMRI and fNIRS. Neuroimage Clin. 2020;25:102086. doi: 10.1016/j.nicl.2019.102086. Epub 2019 Nov 11.

  PMID: 31790877 BACKGROUND

• Bonne O, Gilboa A, Louzoun Y, Kempf-Sherf O, Katz M, Fishman Y, Ben-Nahum Z, Krausz Y, Bocher M, Lester H, Chisin R, Lerer B. Cerebral blood flow in chronic symptomatic mild traumatic brain injury. Psychiatry Res. 2003 Nov 30;124(3):141-52. doi: 10.1016/s0925-4927(03)00109-4.

  PMID: 14623066 BACKGROUND

• Meier TB, Bellgowan PS, Singh R, Kuplicki R, Polanski DW, Mayer AR. Recovery of cerebral blood flow following sports-related concussion. JAMA Neurol. 2015 May;72(5):530-8. doi: 10.1001/jamaneurol.2014.4778.

  PMID: 25730545 BACKGROUND

• Ware JB, Dolui S, Duda J, Gaggi N, Choi R, Detre J, Whyte J, Diaz-Arrastia R, Kim JJ. Relationship of Cerebral Blood Flow to Cognitive Function and Recovery in Early Chronic Traumatic Brain Injury. J Neurotrauma. 2020 Oct 15;37(20):2180-2187. doi: 10.1089/neu.2020.7031. Epub 2020 Jun 11.

  PMID: 32349614 BACKGROUND

• Ding K, Tarumi T, Tomoto T, Mccolloster M, Le T, Dieppa M, Diaz-Arrastia R, Bell K, Madden C, Cullum CM, Zhang R. Impaired cerebral blood flow regulation in chronic traumatic brain injury. Brain Res. 2020 Sep 15;1743:146924. doi: 10.1016/j.brainres.2020.146924. Epub 2020 Jun 4.

  PMID: 32505751 BACKGROUND

• VA/DoD Clinical Practice Guideline for the Management of Concussion-Mild Traumatic Brain Injury (2016).

  BACKGROUND

• Tulsky DS, Carlozzi NE, Holdnack J, Heaton RK, Wong A, Goldsmith A, Heinemann AW. Using the NIH Toolbox Cognition Battery (NIHTB-CB) in individuals with traumatic brain injury. Rehabil Psychol. 2017 Nov;62(4):413-424. doi: 10.1037/rep0000174.

  PMID: 29265862 BACKGROUND

• Tyner CE, Boulton AJ, Sherer M, Kisala PA, Glutting JJ, Tulsky DS. Development of Composite Scores for the TBI-QOL. Arch Phys Med Rehabil. 2020 Jan;101(1):43-53. doi: 10.1016/j.apmr.2018.05.036. Epub 2018 Jul 3.

  PMID: 31875840 BACKGROUND

• Tulsky DS, Kisala PA, Victorson D, Carlozzi N, Bushnik T, Sherer M, Choi SW, Heinemann AW, Chiaravalloti N, Sander AM, Englander J, Hanks R, Kolakowsky-Hayner S, Roth E, Gershon R, Rosenthal M, Cella D. TBI-QOL: Development and Calibration of Item Banks to Measure Patient Reported Outcomes Following Traumatic Brain Injury. J Head Trauma Rehabil. 2016 Jan-Feb;31(1):40-51. doi: 10.1097/HTR.0000000000000131.

  PMID: 25931184 BACKGROUND

• Tulsky DS, Kisala PA. An Overview of the Traumatic Brain Injury-Quality of Life (TBI-QOL) Measurement System. J Head Trauma Rehabil. 2019 Sep/Oct;34(5):281-288. doi: 10.1097/HTR.0000000000000531. No abstract available.

  PMID: 31498227 BACKGROUND

• Zhang R, Zuckerman JH, Giller CA, Levine BD. Transfer function analysis of dynamic cerebral autoregulation in humans. Am J Physiol. 1998 Jan;274(1 Pt 2):H233-41. doi: 10.1152/ajpheart.1998.274.1.h233.

  PMID: 9458872 BACKGROUND

• Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB; international Cerebral Autoregulation Research Network (CARNet). Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network. J Cereb Blood Flow Metab. 2016 Apr;36(4):665-80. doi: 10.1177/0271678X15626425. Epub 2016 Jan 18.

  PMID: 26782760 BACKGROUND

• Caldas J, Cardim D, Edmundson P, Morales J, Feng A, Ashley JD, Park C, Valadka A, Foreman M, Cullum M, Sharma K, Liu Y, Zhu D, Zhang R, Ding K. Study protocol: Cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury -CAPCOG-TBI. Front Neurol. 2024 Oct 16;15:1465226. doi: 10.3389/fneur.2024.1465226. eCollection 2024.

  PMID: 39479003 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples look at

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Kan Ding, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kan Ding, MD

CONTACT

214-648-3571; kan.ding@utsouthwestern.edu

Jill Morales, MS

CONTACT

214-648-3571; Epitbiresearch@utsouthwestern.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: June 28, 2024
• Study Start: September 1, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Time frame of study protocol is to be determine depending on manuscript submission and revision timeline.
• Access Criteria: Criteria will be assessed as data and timelines become solidified.

Locations

US (3)