Ignite Creation Date:
2024-07-17 @ 11:05 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06480838
Status:
RECRUITING
Last Update Posted:
2024-06-28
First Post:
2024-06-24
Brief Title:
Cerebral Autoregulation Brain Perfusion and Neurocognitive Outcomes After Traumatic Brain Injury
Sponsor:
University of Texas Southwestern Medical Center
Organization:
University of Texas Southwestern Medical Center
Study Overview
Official Title:
Cerebral Autoregulation Brain Perfusion and Neurocognitive Outcomes After Traumatic Brain Injury
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CAPCOG-TBI
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
Detailed Description:
Nonfatal traumatic brain injury TBI is a leading cause of disability in adults with an estimated economic cost of approximately 406 billion for the US population The quality of life of TBI survivors is highly dependent on the extent of cognitive recovery after injury Of note about 65 of moderate to severe traumatic brain injury msTBI survivors continue to experience cognitive symptoms including impaired memory slow processing speed and poor attention span years after injury with broad individual variability Epidemiological studies also suggest that TBI is a risk factor for Alzheimers Disease AD and AD-related dementias ADRD Further understanding of the pathophysiological mechanisms by which TBI contributes to progressive cognitive declinedementia is a prominent research priority for the NIH
Although TBI and ADRD have different etiologies mounting evidence indicates that cerebrovascular dysfunction occurs in both TBI and ADRD Impaired cerebral autoregulation CA and brain hypoperfusion are well documented after acute TBI which are associated with unfavorable functional outcomes at 6 months Our recent studies and others using multimodal hemodynamic and imaging approaches have shown that impaired CA and brain hypoperfusion also occur in chronic TBI years after injury and are associated with poor cognitive performance The 2019 ADRD Summit called for further studies to understand the vascular contributions to progressive cognitive impairmentdementia after TBI and develop non-invasive diagnostic approaches The following important questions remain to be addressed 1 What is the impact of cerebrovascular dysfunction after acute TBI on short- and long-term cognitive outcomes 2 What is the temporal relationship between the recovery of cerebrovascular function and cognitive outcome after TBI and 3 Is there a relationship between changes in cerebrovascular function and post-TBI neurodegeneration as assessed through changes in brain volume and axonal integrity
The overarching goal of this proposal is to determine whether acute subacute and chronic cerebrovascular dysfunction measured by CA and brain perfusion after msTBI are associated with cognitive outcomes and neurodegeneration after 12 months We hypothesize that the degree of cerebrovascular dysfunction assessed during the acute stage 1 week postinjury and its poor recovery during the first year are associated with poor cognitive outcomes brain volume loss and axonal damage at 12 months postinjury We propose a longitudinal study with 100 adults who sustained a single msTBI19 and 30 controls with orthopedic trauma only The primary cognitive outcome is the NIH Toolbox Cognitive Battery NIH_TB fluid composite score at 12 months postinjury Secondary clinical outcomes include the Glasgow Outcome Score-Extended GOSE and Traumatic Brain Injury Quality of Life TBI-QOL Brain volume loss and axonal integrity will be assessed using MRI Our team has complementary expertise and research experience in TBI clinical care cognitive outcomes after TBI agingdementia cerebrovascular physiology and neuroimaging to successfully conduct this project
Aim 1 To determine the associations of cerebrovascular dysfunction assessed during the acute stage of msTBI 1 week postinjury with cognitive outcome at 1 year We will measure dynamic CA and brain perfusion using non-invasive multimodality approaches including 2D duplex ultrasonography for cerebral blood flow CBF transcranial Doppler TCD for CBF velocity CBFV near-infrared spectroscopy NIRS for regional brain tissue oxygenation and finger arterial photoplethysmography for beat-to-beat arterial blood pressure ABP CA will be quantified by dynamic changes in ABP and CBFV and brain tissue oxygenation We hypothesize that the degree of cerebrovascular dysfunction during the acute stage of brain injury is inversely associated with 1 cognitive performance and 2 the GOSE and TBI-QOL score at 1 year postinjury
Aim 2 To determine the temporal associations between the recovery of cerebrovascular function and cognitive outcomes after msTBI Dynamic CA and brain perfusion will be measured at 3 6 and 12 months postinjury We hypothesize that the extent of cerebrovascular function recovery after TBI is associated temporally with 1 cognitive outcomes and 2 the GOSE and TBI-QOL score at 1 year postinjury
Aim 3 To determine the temporal associations of acute cerebrovascular dysfunction and its recovery with the imaging biomarkers of neurodegeneration after msTBI We will perform state-of-the-art MRI studies of brain structure and function at 3 months and 12 months postinjury Brain imaging biomarkers will include whole and regional brain volumes and white matter axonal integrity We hypothesize that the severity of acute cerebrovascular dysfunction and its poor recovery are associated with brain volume loss and axonal damage and the associations between cerebrovascular dysfunction and cognitive outcome after TBI are mediated by the brain structural changes
The findings from this study will improve our understanding of cerebrovascular contributions to cognitive and functional outcomes after TBI This study will also provide the urgently needed knowledge of potential pharmacological and non-pharmacological therapies targeting cerebrovascular function to improve cognition and slow neurodegeneration after TBI
Although TBI and ADRD have different etiologies mounting evidence indicates that cerebrovascular dysfunction occurs in both TBI and ADRD Impaired cerebral autoregulation CA and brain hypoperfusion are well documented after acute TBI which are associated with unfavorable functional outcomes at 6 months Our recent studies and others using multimodal hemodynamic and imaging approaches have shown that impaired CA and brain hypoperfusion also occur in chronic TBI years after injury and are associated with poor cognitive performance The 2019 ADRD Summit called for further studies to understand the vascular contributions to progressive cognitive impairmentdementia after TBI and develop non-invasive diagnostic approaches The following important questions remain to be addressed 1 What is the impact of cerebrovascular dysfunction after acute TBI on short- and long-term cognitive outcomes 2 What is the temporal relationship between the recovery of cerebrovascular function and cognitive outcome after TBI and 3 Is there a relationship between changes in cerebrovascular function and post-TBI neurodegeneration as assessed through changes in brain volume and axonal integrity
The overarching goal of this proposal is to determine whether acute subacute and chronic cerebrovascular dysfunction measured by CA and brain perfusion after msTBI are associated with cognitive outcomes and neurodegeneration after 12 months We hypothesize that the degree of cerebrovascular dysfunction assessed during the acute stage 1 week postinjury and its poor recovery during the first year are associated with poor cognitive outcomes brain volume loss and axonal damage at 12 months postinjury We propose a longitudinal study with 100 adults who sustained a single msTBI19 and 30 controls with orthopedic trauma only The primary cognitive outcome is the NIH Toolbox Cognitive Battery NIH_TB fluid composite score at 12 months postinjury Secondary clinical outcomes include the Glasgow Outcome Score-Extended GOSE and Traumatic Brain Injury Quality of Life TBI-QOL Brain volume loss and axonal integrity will be assessed using MRI Our team has complementary expertise and research experience in TBI clinical care cognitive outcomes after TBI agingdementia cerebrovascular physiology and neuroimaging to successfully conduct this project
Aim 1 To determine the associations of cerebrovascular dysfunction assessed during the acute stage of msTBI 1 week postinjury with cognitive outcome at 1 year We will measure dynamic CA and brain perfusion using non-invasive multimodality approaches including 2D duplex ultrasonography for cerebral blood flow CBF transcranial Doppler TCD for CBF velocity CBFV near-infrared spectroscopy NIRS for regional brain tissue oxygenation and finger arterial photoplethysmography for beat-to-beat arterial blood pressure ABP CA will be quantified by dynamic changes in ABP and CBFV and brain tissue oxygenation We hypothesize that the degree of cerebrovascular dysfunction during the acute stage of brain injury is inversely associated with 1 cognitive performance and 2 the GOSE and TBI-QOL score at 1 year postinjury
Aim 2 To determine the temporal associations between the recovery of cerebrovascular function and cognitive outcomes after msTBI Dynamic CA and brain perfusion will be measured at 3 6 and 12 months postinjury We hypothesize that the extent of cerebrovascular function recovery after TBI is associated temporally with 1 cognitive outcomes and 2 the GOSE and TBI-QOL score at 1 year postinjury
Aim 3 To determine the temporal associations of acute cerebrovascular dysfunction and its recovery with the imaging biomarkers of neurodegeneration after msTBI We will perform state-of-the-art MRI studies of brain structure and function at 3 months and 12 months postinjury Brain imaging biomarkers will include whole and regional brain volumes and white matter axonal integrity We hypothesize that the severity of acute cerebrovascular dysfunction and its poor recovery are associated with brain volume loss and axonal damage and the associations between cerebrovascular dysfunction and cognitive outcome after TBI are mediated by the brain structural changes
The findings from this study will improve our understanding of cerebrovascular contributions to cognitive and functional outcomes after TBI This study will also provide the urgently needed knowledge of potential pharmacological and non-pharmacological therapies targeting cerebrovascular function to improve cognition and slow neurodegeneration after TBI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R01NS129934-01A1 | NIH | None | None |