Neurocognitive Impairment Assessment in Symptomatic Carotid Occlusion Recanalized Endovascularly
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Change in Montreal Cognitive Assessment (MoCA) Score
研究概览
简要总结
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
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Prospective randomized open blinded end-point (PROBE) study
入排标准
- 年龄范围
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Endovascular arm
Subjects meet all inclusion criteria and were randomized to intervention
干预措施: Endovascular intervention (Procedure)
Medical arm
Subjects meet all inclusion criteria and were randomized to best medical management
干预措施: Aspirin and Clopidogrel (maximal medical Therapy) (Drug)
Non-Randomized Arm
Subject meets all inclusion criteria EXCEPT abnormal CTP. Subjects are not randomized and are eligible for only best medical management
干预措施: Aspirin and Clopidogrel (maximal medical Therapy) (Drug)
结局指标
主要结局
Change in Montreal Cognitive Assessment (MoCA) Score
时间窗: Baseline, 6 months, 12 months
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.
Change in Composite Cognitive Score
时间窗: Baseline, 6 months, 12 months
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.
次要结局
- 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)