NeuroCognition After Carotid Recanalization (NIA-SCORE)

Neurocognitive Impairment Assessment in Symptomatic Carotid Occlusion Recanalized Endovascularly

Complete occlusion of the Internal carotid artery (ICA) by atherosclerotic disease (COICA) causes approximately 15%-25% of ischemic strokes in the carotid artery distribution. Patients treated with medical therapy have a 7%-10% risk of recurrent stroke per year for any stroke and a 5%-8% risk per year for ipsilateral ischemic stroke during the first 2 years after ICA occlusion. Internal carotid artery occlusion causes an estimated 61,000 first-ever strokes per year in the US an incidence more than twice the annual occurrence of ruptured intracranial aneurysms Additionally, 40% of subjects with COICA who present with transient ischemic attack (TIA) and 70% of COICA who present with stroke have cognitive decline with increased risk of vascular dementia and Alzheimer's' disease (AD) with time (2,3).

Symptomatic COICA subjects are at increased risk of developing cognitive impairment and progressive development of vascular dementia and AD with time. Our proposal leverages several compelling retrospective and prospective preliminary data from human to perform this exploratory trial with go/no-go criteria to proceed to a phase 3 based on the data generated

Study Overview

• Status: Completed
• Conditions: Stroke; Cognition Disorder; Occlusion Carotid
• Intervention / Treatment: Procedure: Endovascular intervention; Drug: Aspirin and Clopidogrel (maximal medical Therapy)

Detailed Description

Study Design:

Prospective randomized open blinded end-point (PROBE) study

This is a phase 2 randomized single-center open label clinical trial with randomization of 1:1 to either best medical management vs. best medical management and endovascular revascularization of COICA.

Screening, Enrolling, & Randomization:

All subjects who presents to our tertiary hospital with a diagnosis of COICA will undergo full evaluation including 1) documenting previous history of transient ischemic attack (TIA) and/or stroke; 2) cervical and brain CT angiography (CTA) to document complete occlusion; 3) CT perfusion (CTP) to assess for presence of penumbra evident by increased mean transient time (MTT) in the ipsilateral side of COICA; and 4) Montreal cognitive assessment (MoCA) score. If any subject is found to have complete occlusion of COICA, evident of abnormal/prolongation of MTT on CTP, previous history of TIA and or stroke, and MoCA <26 or abnormal response on another neuropsychological assessment preformed in the screening battery, then further evaluation is obtained including: MRI spectroscopy to assess for presence/absence of lactate in the ipsilateral watershed area (centrum semiovale), and size of ipsilateral hippocampus and amygdala, additional cognitive testing battery, and digital subtraction angiography (DSA) to document adequately the type of COICA the subject have (type A-D).

If a subject meets all inclusion criteria (complete occlusion, MoCA <26 and/or abnormal other neuropsychological test result, abnormal CTP) they will be randomized, after consent is obtained. If all inclusion criteria are met other than the CTP, they will be enrolled but not randomized. These subjects will only be eligible for best medical management- not surgical intervention.

If any subject does not have complete occlusion or abnormal MoCA >26 or other neuropsychological assessment, then the subject is excluded and no further testing needed (see exclusion criteria).

If the subject meets all inclusion criteria, then a baseline of complete neurological testing, full demographics, CTA or MRA, CTP, MoCA, additional neurological testing, MRI spectroscopy and DSA are obtained and subject is randomized 1:1 to either best medical management or best medical management + endovascular balloon angioplasty and stenting. Follow up clinic visits are arranged at 6 and 12 months. Repeat testing of MoCA and additional cognitive testing battery are done at these clinical follow-up visits (6 and 12 months). MRI of the brain and is done at 6 and 12 months. DSA is performed at 1 year follow-up for intervention subjects to assess brain bio-markers and revascularization respectively.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 21
• Complete occlusion of cervical ICA on imaging studies (MRA or CTA) and confirmed with DSA
• History of TIA or stroke
• Increased MTT and/or time to peak (TTP) on CT perfusion as defined as T Max threshold of > 10cc > 4 seconds in the territory of the occluded carotid specifically in the MCA territory when compared to the opposite unaffected hemisphere (not required for observational cohort)
• All occlusion is due to atherosclerotic disease
• MoCA < 26 or abnormal result on another test in the battery (abnormal defined as 1.5 SD below age/ gender/ education matched norms).
• Baseline MoCA assessed by the neurosurgery team or neuropsychology team
• Failed best medical treatment (defined below)
• Class A and B on COICA Classification
• Study team able to gain consent from subject or legal adult representative (LAR)

Exclusion Criteria:

• Non-atherosclerotic occlusive disease that may have caused the occlusion, including moyamoya, dissection, trauma or other causes
• Tandem occlusion
• No evidence of penumbra on CT perfusion
• Severe co-morbid diseases: Chronic Kidney Disease (CKD) stages 4 or 5, end-stage renal disease, liver cirrhosis; Chronic Obstructive Pulmonary Disease (COPD) requiring home oxygen; terminal illness such as cancer; Parkinson disease or other neurodegenerative diseases; severe congestive heart failure; seizures; debilitating stroke, Modified Rankin Score (mRS) ≥ 3
• Short life expectancy due to cancer or other co-morbid diseases
• Class D on COICA classification
• Normal neuropsychological battery test results
• Subject unwilling to randomized to surgical procedure
• Pregnant or risk of becoming pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endovascular arm; Subjects meet all inclusion criteria and were randomized to intervention	Procedure: Endovascular intervention; Endovascular angioplasty of the occluded carotid using balloon angioplasty and reconstruction with stents: coronary stents distally (Rebel, Boston Scientific; Vision, Abbott Vascular) and carotid stents proximal (Acculink and Xcat, Abbott Vascular) Patients will stay on their aspirin 325 mg and clopidogrel 75 mg
Active Comparator: Medical arm; Subjects meet all inclusion criteria and were randomized to best medical management	Drug: Aspirin and Clopidogrel (maximal medical Therapy); Best Medical Management: daily dual antiplatelet therapy (aspirin: 325 mg p.o. qd and Clopidogrel: 75 mg p.o. qd), optimization of systolic blood pressure (120 -140 mmHg), and smoking cessation.
Active Comparator: Non-Randomized Arm; Subject meets all inclusion criteria EXCEPT abnormal CTP. Subjects are not randomized and are eligible for only best medical management	Drug: Aspirin and Clopidogrel (maximal medical Therapy); Best Medical Management: daily dual antiplatelet therapy (aspirin: 325 mg p.o. qd and Clopidogrel: 75 mg p.o. qd), optimization of systolic blood pressure (120 -140 mmHg), and smoking cessation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montreal Cognitive Assessment (MoCA) Score	The MoCA is a screening tool used to assess cognitive function. The possible score range is 0 to 30, with higher scores indicating better cognitive performance.	Baseline, 6 months, 12 months
Change in Composite Cognitive Score	This outcome reflects overall cognition. The composite z score is based on average z scores for the tests for each subject (sum of the z scores divided by the number of tests included) from a specifically designed battery of 14 cognitive tests: Montreal Cognitive Assessment (MoCA),Wide Range Achievement Test-5 (WRAT-5); Wechsler Adult Intelligence Scale - IV (WAIS-IV); WAIS-IV, Coding subtest; WAIS-IV, Matrix Reasoning subtest; Hopkins Verbal Learning Test; Benton Visual Retention Test (BVRT); Controlled Oral Word Association (COWA) Test; Boston Naming Test; Boston Diagnostic Aphasia Examination, Complex Ideational Material subtest; Trail-Making Test, part A and part B; Beck Depression Inventory-Fast Screen (BDI-FS); Iowa Scales of Personality Change (ISPC). A Z-score of 0 represents no change. Standard deviations above 0 represent better outcomes; standard deviations below 0 represent worse outcomes.	Baseline, 6 months, 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Stroke Within 30 Days Post Procedure	Up to 30 days post procedure
Number of Participants With Intracranial Hemorrhage Within 72 Hours Post Procedure	Up to 72 hours post procedure
Number of Participant Deaths	Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Transit Time (MTT) on CT Perfusion	MTT is defined as the average time, in seconds, that circulating blood cells needs to pass within a determinate volume of brain. It is assessed as part of the CT perfusion protocol.	Baseline, 12 months
Change in Size of Hippocampus	The change in size of hippocampus in the ipsilateral side of COICA (t-test), at enrollment vs. 1 year.	Baseline, 6 months, 12 months
Change in Size of Amygdala	The change in size of amygdala in the ipsilateral side of COICA (t-test), at enrollment vs. 1 year.	Baseline, 6 months, 12 months
Number of Participants With the Presence of Lactate on 1H-MRI Spectroscopy	Presence of lactate determined by MRI spectroscopy in centrum semiovale in the ipsilateral side of chronic occlusion of the internal carotid artery (COICA).	Baseline, 6 months, 12 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: David Hasan, MD, Duke University

Publications and helpful links

General Publications

• Zanaty M, Roa JA, Jabbour PM, Samaniego EA, Hasan DM. Recanalization of the Chronically Occluded Internal Carotid Artery: Review of the Literature. World Neurosurg X. 2019 Nov 21;5:100067. doi: 10.1016/j.wnsx.2019.100067. eCollection 2020 Jan.
• Hudson JS, Zanaty M, Wadman V, Nakagawa D, Ishii D, Roa JA, Al Kasabz S, Limaye K, Rossen JD, Jabbour P, Adams HP Jr, Samaniego EA, Hasan DM. Bradycardia and Asystole in Patients Undergoing Symptomatic Chronically Occluded Internal Carotid Artery Recanalization. World Neurosurg. 2019 Nov;131:e211-e217. doi: 10.1016/j.wneu.2019.07.125. Epub 2019 Jul 23.
• Limaye K, Zanaty M, Hudson J, Nakagawa D, Al Kasab S, Alvarez C, Dandapat S, Kung DK, Ortega-Gutierrez S, Jabbour P, Samaniego EA, Hasan D. The Safety and Efficacy of Continuous Tirofiban as a Monoantiplatelet Therapy in the Management of Ruptured Aneurysms Treated Using Stent-Assisted Coiling or Flow Diversion and Requiring Ventricular Drainage. Neurosurgery. 2019 Dec 1;85(6):E1037-E1042. doi: 10.1093/neuros/nyz226.
• Zanaty M, Samaniego EA, Hasan DM. Letter to the Editor Regarding "Estimation and Recanalization of Chronic Occluded Internal Carotid Artery: Hybrid Operation by Carotid Endarterectomy and Endovascular Angioplasty". World Neurosurg. 2019 Jan;121:287. doi: 10.1016/j.wneu.2018.09.033. No abstract available.
• Zanaty M, Samaniego EA, Teferi N, Kung DK, Nakagawa D, Hudson J, Ortega-Gutierrez S, Allan L, Jabbour P, Hasan DM. Hybrid Surgery for Internal Carotid Artery Revascularization. World Neurosurg. 2019 Jan;121:137-144. doi: 10.1016/j.wneu.2018.09.230. Epub 2018 Oct 9.
• Zanaty M, Howard S, Roa JA, Alvarez CM, Kung DK, McCarthy DJ, Samaniego EA, Nakagawa D, Starke RM, Limaye K, Al Kasab S, Chalouhi N, Jabbour P, Torner J, Tranel D, Hasan D. Cognitive and cerebral hemodynamic effects of endovascular recanalization of chronically occluded cervical internal carotid artery: single-center study and review of the literature. J Neurosurg. 2019 Mar 29;132(4):1158-1166. doi: 10.3171/2019.1.JNS183337. Print 2020 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): March 14, 2024
• Study Completion (Actual): March 14, 2024

Study Registration Dates

• First Submitted: December 31, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 9, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Aspirin
• Other Study ID Numbers: PRO00110125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No