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Assessing Neurocognition After Cerebrovascular Intervention

Primary Purpose

Carotid Artery Diseases, Neurocognitive Dysfunction

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Neurocognitive Assessments
Measurements of inflammatory biomarkers
Carotid Artery Stenting
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carotid Artery Diseases focused on measuring carotid stenosis, neurocognition, carotid stenting, circle of willis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • patients >18 years of age
  • ultrasound evidence of carotid stenosis; in which the patient has either 50% or greater symptomatic carotid stenosis or 70% or greater asymptomatic carotid stenosis.

Exclusion Criteria:

  1. patients <18 years of age
  2. patients with without compatibility for MRI
  3. patients requiring carotid stenting for reasons not related to long-standing stenosis
  4. patients requiring emergency carotid stenting for acute symptoms such as crescendo transient ischemic attacks, intolerance of physiologic blood pressure.
  5. Patients that do not have appropriate capacity (i.e. understand the risks and benefits associated with this study) or are unable to consent for themselves will not be included in this study.

Sites / Locations

  • UCSD Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control Group

Intervention Group

Arm Description

Patients, as outlined by NASCET criteria, will have between 50 symptomatic stenosis or 70% asymptomatic stenosis of the carotid artery. Patients, undergoing carotid artery stenting for carotid stenosis, will undergo cognitive testing at 2 time points before intervention (1 months, and 2 months). The two preoperative time points will serve as the control group.

Patients, as outlined by NASCET criteria, will have between 50 symptomatic stenosis or 70% asymptomatic stenosis of the carotid artery. Patients, undergoing carotid artery stenting for carotid stenosis, will undergo cognitive testing at 2 time points after invention (1 month and 2 months). The two postoperative time points will serve as the intervention group.

Outcomes

Primary Outcome Measures

Neurocognition
Neurocognition will be assessed through a battery of 8 tests to measure cognitive capacity across a range of neurocognitive domains.

Secondary Outcome Measures

TNF-α
Inflammatory Markers: tumor necrosis factor-α
IL-6
Inflammatory Markers: IL-6
IL-1β
Inflammatory Markers: IL-1β
CRP
Inflammatory Markers: CRP
IFN-γ
Inflammatory Markers: IFN-γ
sICAM-1
Inflammatory Markers: sICAM-1
sVCAM-1
Inflammatory Markers: sVCAM-1

Full Information

First Posted
November 13, 2017
Last Updated
February 8, 2021
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT03344276
Brief Title
Assessing Neurocognition After Cerebrovascular Intervention
Official Title
Assessing Neurocognition After Cerebrovascular Intervention
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2021 (Anticipated)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Decreased blood flow to the brain can cause decreased cognitive function. Carotid disease can result in decreased blood flow to the brain. The investigators seek to assess this relationship prospectively through performing a battery of neurocognitive assessments, collection of serum markers of inflammation, and through neuroimaging at two points before intervention (2 months and 1 month before stenting) and at two points after intervention (1 month and 2 months after intervention). The goal is to provide prospective evidence to identify the extent to which carotid stenosis and hypoperfusion of the brain results in diminished neurocognitive performance, and see if serum biomarkers before and after stenting correlate with these findings.
Detailed Description
Patients are being asked to partake in this study because the PI has decided on clinical grounds as outlined in the clinical trial, NASCET, (either asymptomatic 70% carotid stenosis or symptomatic >50% carotid stenosis) that CAS or CEA is indicated. The only aspect of the study that is research is the cognitive testing, the inflammatory blood markers, and components of the neuroimaging. In this pilot study 20 patients, undergoing CAS for CS, will undergo cognitive testing at 2 time points before intervention (1 months, and 2 months) and at 2 time points after invention (1 month and 2 months). The two preoperative time points will serve as the control group and the two postoperative time points will serve as the intervention group. Patients, as outlined by NASCET criteria, will have between 50% symptomatic stenosis or 70% asymptomatic stenosis of the carotid artery. If patients present acutely or are otherwise clinically determined to be unstable (e.g. crescendo TIAs, intolerance of normal physiologic blood pressure, etc.) due to their carotid disease, they will excluded from the study. Patients will serve as their own controls, classifying the study as a within-subjects design. Patients will also have venous blood drawn to ascertain the change in serum markers associated with endothelial dysfunction and inflammation before and after intervention. Finally, patients will have magnetic resonance imaging (MRA) one month before intervention and 2 months after intervention in order to assess changes in global cerebral blood flow. The following neurocognitive tests will take place - the duration of all typically takes one hour to complete. Memory measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) and Rey Complex Figure Executive function assessed with Trails A and B Attention/processing speed measured with Wechsler Adult Intelligence Scale Digit Span and Coding subtests Language assessed with the Multilingual Naming Test and Verbal Fluency Visuospatial abilities measured with Block Design Global cognition measured with Mattis Dementia Rating Scale Estimated premorbid intelligence measured with the American version of the National Adult Reading Test (preoperatively only) Mood assessed with the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) Biomarkers, as a proxy for systemic inflammation will also be collected. The following biomarkers are associated with inflammation-TNF-α, IL-6, IL-1β, CRP, IFN-γ and endothelial cell activation-sICAM sVCAM will be obtained from venous blood (5 ml) and stored at -80° C until the time of electrochemiluminescence assay. As an accompanying measurement of inflammation, complete blood counts will be assessed. R statistical software will be used for the statistical analysis. Fisher exact, chi square, and logistic regression testing will be used to assess categorical data while paired t tests and linear regression models will be used to assess continuous variables. Multivariable univariate logistic and linear regression will be performed to assess if carotid intervention is associated with statistically significant changes in neurocognitive performance or changes in serum biomarker levels. Additional predictors to assess neurocognitive performance will include age, gender, race, degree of carotid stenosis, side of stenosis, prior history of stroke, prior history of neurosurgical or endovascular interventions, presence of coronary artery disease, active malignancy, vasculopathy including diabetes, hypertension, hyperlipidemia, obesity, systemic vascular disease, intracranial atherosclerosis, ultrasound perfusion of intracranial vessels, prior neurocognitive decline: ie prior history of Alzheimer's, degenerative neurological disease. Outcome variables will include standardized neuropsychological measures. The investigators hypothesize a more exuberant neurocognitive response in patients with an incomplete circle of Willis. A dropped model will be performed to prevent overfitting of the regression analysis. A p value less than 0.05 will be used to define statistical significance. The investigators predict that patients will not have a statistically significant change in neurocognitive performance during the three-month and six-week time points prior to intervention-and this will serve as the control period. We predict that 35% of patients will have some improvement in neurocognition after intervention. The sample size calculator to identify a difference in groups at a p<0.05 with a power of 0.8 predicts with 5% attrition determines that 20 patients will be required for the analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carotid Artery Diseases, Neurocognitive Dysfunction
Keywords
carotid stenosis, neurocognition, carotid stenting, circle of willis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
In this pilot study 20 patients, undergoing CAS for CS, will undergo cognitive testing at 2 time points before intervention (1 months, and 2 months) and at 2 time points after invention (1 month and 2 months). The two preoperative time points will serve as the control group and the two postoperative time points will serve as the intervention group. Patients will serve as their own controls, classifying the study as a within-subjects design. Patients will also have venous blood drawn to ascertain the change in serum markers associated with endothelial dysfunction and inflammation before and after intervention. Finally, patients will have magnetic resonance imaging (MRA) one month before intervention and 2 months after intervention in order to assess changes in global cerebral blood flow.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control Group
Arm Type
Active Comparator
Arm Description
Patients, as outlined by NASCET criteria, will have between 50 symptomatic stenosis or 70% asymptomatic stenosis of the carotid artery. Patients, undergoing carotid artery stenting for carotid stenosis, will undergo cognitive testing at 2 time points before intervention (1 months, and 2 months). The two preoperative time points will serve as the control group.
Arm Title
Intervention Group
Arm Type
Experimental
Arm Description
Patients, as outlined by NASCET criteria, will have between 50 symptomatic stenosis or 70% asymptomatic stenosis of the carotid artery. Patients, undergoing carotid artery stenting for carotid stenosis, will undergo cognitive testing at 2 time points after invention (1 month and 2 months). The two postoperative time points will serve as the intervention group.
Intervention Type
Diagnostic Test
Intervention Name(s)
Neurocognitive Assessments
Intervention Description
Patients will undergo carotid artery stenting for 50-70% carotid artery stenosis. Prior to surgery patients will undergo a battery of neurocogntive assessments 1 month and 2 months prior to surgery.
Intervention Type
Diagnostic Test
Intervention Name(s)
Measurements of inflammatory biomarkers
Intervention Description
Patients will undergo carotid artery stenting for 50-70% carotid artery stenosis. After surgery, patients will undergo blood draws to measure for inflammatory biomarkers.
Intervention Type
Procedure
Intervention Name(s)
Carotid Artery Stenting
Intervention Description
Patients will undergo carotid artery stenting for 50-70% carotid artery stenosis.
Primary Outcome Measure Information:
Title
Neurocognition
Description
Neurocognition will be assessed through a battery of 8 tests to measure cognitive capacity across a range of neurocognitive domains.
Time Frame
4 months
Secondary Outcome Measure Information:
Title
TNF-α
Description
Inflammatory Markers: tumor necrosis factor-α
Time Frame
4 months
Title
IL-6
Description
Inflammatory Markers: IL-6
Time Frame
4 months
Title
IL-1β
Description
Inflammatory Markers: IL-1β
Time Frame
4 months
Title
CRP
Description
Inflammatory Markers: CRP
Time Frame
4 months
Title
IFN-γ
Description
Inflammatory Markers: IFN-γ
Time Frame
4 months
Title
sICAM-1
Description
Inflammatory Markers: sICAM-1
Time Frame
4 months
Title
sVCAM-1
Description
Inflammatory Markers: sVCAM-1
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: patients >18 years of age ultrasound evidence of carotid stenosis; in which the patient has either 50% or greater symptomatic carotid stenosis or 70% or greater asymptomatic carotid stenosis. Exclusion Criteria: patients <18 years of age patients with without compatibility for MRI patients requiring carotid stenting for reasons not related to long-standing stenosis patients requiring emergency carotid stenting for acute symptoms such as crescendo transient ischemic attacks, intolerance of physiologic blood pressure. Patients that do not have appropriate capacity (i.e. understand the risks and benefits associated with this study) or are unable to consent for themselves will not be included in this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander Khalessi, MD
Phone
(619) 543-5540
Email
akhalessi@ucsd.edu
First Name & Middle Initial & Last Name or Official Title & Degree
ARVIN WALI, BA, MAS
Phone
7149282722
Email
AWALI@UCSD.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander A Khalessi, MD
Organizational Affiliation
UC San Diego
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David R Santiago-Dieppa, MD
Organizational Affiliation
UC San Diego
Official's Role
Study Director
Facility Information:
Facility Name
UCSD Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David R Santiago-Dieppa, MD
Phone
619-543-5078
Email
drsantiagodieppa@ucsd.edu
First Name & Middle Initial & Last Name & Degree
David R Santiago-Dieppa, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Per institutional review board, data will only be shared with the researchers specified on the research protocol.
Citations:
PubMed Identifier
22222422
Citation
Arntzen KA, Schirmer H, Johnsen SH, Wilsgaard T, Mathiesen EB. Carotid atherosclerosis predicts lower cognitive test results: a 7-year follow-up study of 4,371 stroke-free subjects - the Tromso study. Cerebrovasc Dis. 2012;33(2):159-65. doi: 10.1159/000334182. Epub 2012 Jan 5.
Results Reference
background
PubMed Identifier
21943640
Citation
Baracchini C, Mazzalai F, Gruppo M, Lorenzetti R, Ermani M, Ballotta E. Carotid endarterectomy protects elderly patients from cognitive decline: a prospective study. Surgery. 2012 Jan;151(1):99-106. doi: 10.1016/j.surg.2011.06.031. Epub 2011 Sep 22.
Results Reference
background
PubMed Identifier
10726605
Citation
Shapiro AM, Benedict RH, Schretlen D, Brandt J. Construct and concurrent validity of the Hopkins Verbal Learning Test-revised. Clin Neuropsychol. 1999 Aug;13(3):348-58. doi: 10.1076/clin.13.3.348.1749.
Results Reference
background
PubMed Identifier
11679405
Citation
Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001 Oct 26;89(9):763-71. doi: 10.1161/hh2101.099270.
Results Reference
background
PubMed Identifier
23596467
Citation
Cheng Y, Wang YJ, Yan JC, Zhou R, Zhou HD. Effects of carotid artery stenting on cognitive function in patients with mild cognitive impairment and carotid stenosis. Exp Ther Med. 2013 Apr;5(4):1019-1024. doi: 10.3892/etm.2013.954. Epub 2013 Feb 8.
Results Reference
background
PubMed Identifier
1852179
Citation
North American Symptomatic Carotid Endarterectomy Trial Collaborators; Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, Ferguson GG, Fox AJ, Rankin RN, Hachinski VC, Wiebers DO, Eliasziw M. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991 Aug 15;325(7):445-53. doi: 10.1056/NEJM199108153250701.
Results Reference
background
PubMed Identifier
23103489
Citation
Wendell CR, Waldstein SR, Ferrucci L, O'Brien RJ, Strait JB, Zonderman AB. Carotid atherosclerosis and prospective risk of dementia. Stroke. 2012 Dec;43(12):3319-24. doi: 10.1161/STROKEAHA.112.672527. Epub 2012 Oct 25.
Results Reference
background
PubMed Identifier
25098321
Citation
Sun Q, Xia Z, Qu C, Ruan X, Li J, Cong L, Zheng X, Du Y. Carotid artery stenting ameliorates the cognitive impairment in patients with leukoaraiosis, the ischemic change of cerebral white matter. Tohoku J Exp Med. 2014 Aug;233(4):257-64. doi: 10.1620/tjem.233.257.
Results Reference
background

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Assessing Neurocognition After Cerebrovascular Intervention

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