NIA-SCORE: NeuroCognition After Carotid Recanalization

Sponsor
David Hasan (Other)
Overall Status
Recruiting
CT.gov ID
NCT04219774
Collaborator
(none)
40
Enrollment
1
Location
3
Arms
69.1
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

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

Condition or DiseaseIntervention/TreatmentPhase
  • Procedure: Endovascular intervention
  • Drug: Aspirin and Clopidogrel (maximal medical Therapy)
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
1:1 randomization, 1 non-randomized active comparator arm1:1 randomization, 1 non-randomized active comparator arm
Masking:
Single (Outcomes Assessor)
Masking Description:
Prospective randomized open blinded end-point (PROBE) study
Primary Purpose:
Treatment
Official Title:
Neurocognitive Impairment Assessment in Symptomatic Carotid Occlusion Recanalized
Actual Study Start Date :
May 1, 2020
Anticipated Primary Completion Date :
Feb 1, 2025
Anticipated Study Completion Date :
Feb 1, 2026

Arms and Interventions

ArmIntervention/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.

Outcome Measures

Primary Outcome Measures

  1. MoCA Score [12-month]

    Cognitive outcome assessed by the MontReal Cognitive Assessment score

  2. Composite Cognitive Score [12-month]

    This is one outcome that reflects the overall cognition. The composite cognitive score at 12-month follow-up is assessed by a composite z score based on average z score 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. Scores from tests in the proposed neuropsychological battery will be converted to z-scores. This is the following battery: 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).

Secondary Outcome Measures

  1. Stroke [12-month]

    Incidence of ipsilateral stroke

  2. Hemorrhage [12-month]

    Incidence of ipsilateral cerebral hemorrhage

  3. Death [12-months]

    Rate death

Other Outcome Measures

  1. MTT [12-month]

    Resolution/improvement of increased mean transit time (MTT) on CT perfusion. RABID software will be analyzed using a T-Test, at enrollment vs. 1 year

  2. Size of amygdala [6 and 12-month]

    The change in size of hippocampus in the ipsilateral side of COICA (t-test), at enrollment vs. 1 year

  3. Size of hippocampus [6 and 12-month]

    The change in size of amygdala in the ipsilateral side of COICA (t-test) at enrollment vs. 1 year

  4. Lactate [6 and 12-month]

    Concentration of Lactate on MRI spectroscopy in centrum semiovale in the ipsilateral side of COICA at enrollment vs 1 year.

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 TPP on CTP in the ipsilateral side of the occluded ICA specifically in the middle cerebral artery (MCA) territory when compared to the opposite unaffected hemisphere

  • If this criteria is NOT present: subject may be eligible for non-randomized third arm

  • All occlusion is due to atherosclerotic disease

  • MoCA < 26

Exclusion Criteria:
  • Non-atherosclerotic occlusive disease that may have caused the occlusion, including moyamoya, dissection, trauma or other causes

  • Tandem occlusion

  • No evidence of increased MTT and /or PTT on CT perfusion

  • Severe co-morbid diseases: end-stage renal disease, renal insufficiency, liver cirrhosis, chronic obstructive pulmonary disease (COPD) requiring home oxygen, terminal illness such as cancer, Parkinson disease or other neurodegenerative diseases, severe cognitive heart failure, seizures, debilitating stroke, modified Rankin scale (mRS) ≥3.

  • Short life expectancy due to cancer or other co-morbid diseases

  • Class D on COICA classification

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of Iowa hospitals and ClinicsIowa CityIowaUnited States52242

Sponsors and Collaborators

  • David Hasan

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
David Hasan, Principle investigator, Professor of neurosurgery, Cerebrovascular neurosurgeon, Department of Neurosurgery, University of Iowa hospital and clinics, University of Iowa
ClinicalTrials.gov Identifier:
NCT04219774
Other Study ID Numbers:
  • 201910819
First Posted:
Jan 7, 2020
Last Update Posted:
Nov 18, 2021
Last Verified:
Nov 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 18, 2021