NeuroCognition After Carotid Recanalization

NCT04219774 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO00110125
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Cognition Disorder; Stroke; Occlusion Carotid

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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 Outcomes (4)

• Change in Mean Transit Time (MTT) on CT Perfusion

  Baseline, 12 months

• Change in Size of Hippocampus

  Baseline, 6 months, 12 months

• Change in Size of Amygdala

  Baseline, 6 months, 12 months

Study Arms (3)

Endovascular arm

EXPERIMENTAL

Subjects meet all inclusion criteria and were randomized to intervention

Procedure: Endovascular intervention

Medical arm

ACTIVE COMPARATOR

Subjects meet all inclusion criteria and were randomized to best medical management

Drug: Aspirin and Clopidogrel (maximal medical Therapy)

Non-Randomized Arm

ACTIVE COMPARATOR

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)

Interventions

Endovascular intervention PROCEDURE

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

Endovascular arm

Aspirin and Clopidogrel (maximal medical Therapy) DRUG

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.

Medical arm; Non-Randomized Arm

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (2)

University of Iowa hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Related Publications (6)

• 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.

  PMID: 31872191 BACKGROUND

• 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.

  PMID: 31349074 BACKGROUND

• 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.

  PMID: 31298301 BACKGROUND

• 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.

  PMID: 30925474 BACKGROUND

• 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.

  PMID: 30557930 BACKGROUND

• 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.

  PMID: 30312821 BACKGROUND

MeSH Terms

Conditions

Cognition Disorders; Stroke

Interventions

Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The Observation Arm was not included in comparison. It is a non-equivalent group because patients included in the Arm if they were ineligible based on baseline measures and consent to randomization.

Results Point of Contact

• Title: David Hasan, MD, MSc
• Organization: Duke University

david.hasan@duke.edu

919-684-7777

Study Officials

• David Hasan, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Prospective randomized open blinded end-point (PROBE) study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1 randomization, 1 non-randomized active comparator arm

Study Record Dates

• First Submitted: December 31, 2019
• First Posted: January 7, 2020
• Study Start: May 1, 2020
• Primary Completion: March 14, 2024
• Study Completion: March 14, 2024
• Last Updated: May 9, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)