Assessing Neurocognition After Cerebrovascular Intervention

NCT ID: NCT03344276

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-15
• Study Completion Date: 2025-12-31

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.

1. Memory measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) and Rey Complex Figure

2. Executive function assessed with Trails A and B

3. Attention/processing speed measured with Wechsler Adult Intelligence Scale Digit Span and Coding subtests

4. Language assessed with the Multilingual Naming Test and Verbal Fluency

5. Visuospatial abilities measured with Block Design

6. Global cognition measured with Mattis Dementia Rating Scale

7. Estimated premorbid intelligence measured with the American version of the National Adult Reading Test (preoperatively only)

8. 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.

Conditions

Carotid Artery Diseases; Neurocognitive Dysfunction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 before intervention (1 months, and 2 months). The two preoperative time points will serve as the control group.

Group Type: ACTIVE_COMPARATOR

Neurocognitive Assessments

Intervention Type: DIAGNOSTIC_TEST

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.

Measurements of inflammatory biomarkers

Intervention Type: DIAGNOSTIC_TEST

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 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.

Group Type: EXPERIMENTAL

Neurocognitive Assessments

Intervention Type: DIAGNOSTIC_TEST

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.

Measurements of inflammatory biomarkers

Intervention Type: DIAGNOSTIC_TEST

Patients will undergo carotid artery stenting for 50-70% carotid artery stenosis. After surgery, patients will undergo blood draws to measure for inflammatory biomarkers.

Carotid Artery Stenting

Intervention Type: PROCEDURE

Patients will undergo carotid artery stenting for 50-70% carotid artery stenosis.

Interventions

Neurocognitive Assessments

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

Measurements of inflammatory biomarkers

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: DIAGNOSTIC_TEST

Carotid Artery Stenting

Patients will undergo carotid artery stenting for 50-70% carotid artery stenosis.

Intervention Type: PROCEDURE

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Alexander A. Khalessi MD MS FAANS

Acting Clinical Chief UCSD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexander A Khalessi, MD

Role: PRINCIPAL_INVESTIGATOR

UC San Diego

David R Santiago-Dieppa, MD

Role: STUDY_DIRECTOR

UC San Diego

Locations

UCSD Medical Center

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Alexander Khalessi, MD

Role: CONTACT

akhalessi@ucsd.edu

(619) 543-5540

ARVIN WALI, BA, MAS

Role: CONTACT

AWALI@UCSD.EDU

7149282722

Facility Contacts

David R Santiago-Dieppa, MD

Role: primary

drsantiagodieppa@ucsd.edu

6195435078

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

170103

Identifier Type: -

Identifier Source: org_study_id