Study of Carotid Occlusion and Neurocognition (RECON)

颈动脉闭塞和神经认知研究 (RECON)

• 批准号: 6989045
• 负责人: Randolph S Marshall
• 金额: $ 40.03万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-06 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989045
• 关键词: brain circulation; carotid artery; cerebrovascular occlusions; clinical research; cognition; functional ability; human subject; human therapy evaluation; neuropsychological tests; patient oriented research; stroke; stroke therapy

DESCRIPTION (provided by applicant): Clinical trials for the treatment of carotid artery disease have focused almost exclusively on a single outcome --prevention of recurrent stroke -- yet accumulating evidence suggests that cognitive function is affected by carotid artery disease and hemodynamic impairment. We propose an ancillary study to the newly-funded, NINDS-sponsored Carotid Occlusion Surgery Study (COSS) to test the hypothesis that cognitive outcomes are relevant and important to measure in the treatment of cerebral hypoperfusion. The COSS trial is designed to test the hypothesis that EC-IC bypass can reduce by 40% the rate of recurrent stroke at 2 years in patients with recently symptomatic internal carotid artery occlusion and Stage II hemodynamic failure as measured by increased oxygen extraction fraction (OEF) on positron emission tomography (PET). We propose to evaluate the cognitive status in randomized COSS patients using global and hemisphere-specific neurocognitive tests in a battery that takes less than an hour to administer. Our specific aim is to determine whether patients who have symptomatic, unilateral carotid artery occlusion and PET evidence of stage II cerebral hemodynamic failure who do not reach a COSS endpoint (ipsilateral stroke) will have better cognitive function 3 months and 2 years following EC-IC bypass compared with an identical group of patients treated with best medical therapy alone. The impetus for our proposal comes from preliminary data in which we demonstrated a quantitative relationship between cerebral blood flow (CBF) and higher cortical function in the setting of carotid artery test occlusion. We and others have further demonstrated cognitive improvement in case series studies of patients with carotid stenosis or occlusion treated with endarterectomy or extracranial-intracranial (EC-IC) bypass. In our proposed study approximately 294 patients will have neurocognitive testing at time of randomization; then 30 days, 3 months, and 2 years after EC-IC bypass or the equivalent time point in the COSS medical arm. All patients will undergo a follow-up PET scan at 3 months to determine actual OEF status. Adjusting for anticipated drop-out due to end-points in the COSS trial, we will have 80% power to detect a 0.5 SD difference in cognitive scores at an alpha level of 0.05. Correlation of cognitive scores with COSS disability and quality of life measures will be made to establish the clinical relevance of change in cognition. In addition to the benefit to the COSS trial if reperfusion surgery can be shown to be improve cognition, positive findings in this study could pave the way for the use of similar cognitive measures in other carotid disease treatment trials.

描述（由申请人提供）：治疗颈动脉疾病的临床试验几乎完全集中在单一结果上 - 预防复发性中风 - 但积累的证据表明认知功能受颈动脉疾病和血液动力学障碍的影响。我们对新资助的Ninds赞助的颈动脉闭塞手术研究（COSS）提出了一项辅助研究，以检验以下假设：认知结果对治疗大脑垂直灌注至关重要。 COSS试验旨在检验以下假设：在最近有症状的内部颈内动脉闭塞和II期血液动力学衰竭的患者中，EC-IC旁路可以降低40％的复发性中风速率，这是通过对正电子发射断层扫描（PET）上增加的氧气提取分数（OEF）来衡量的。我们建议在电池中使用全球和半球特异性神经认知测试评估随机COSS患者的认知状况，该测试需要不到一个小时才能进行。我们的具体目的是确定患有症状，单侧颈动脉阻塞的患者和II期脑血液动力学衰竭的证据是否没有达到COSS端点（IPSILIAD PROTOKE）在EC-IC旁路后3个月零2年的患者与单独使用最佳药物治疗相比，EC-IC旁路后的认知功能更好。提案的动力来自初步数据，在颈动脉测试闭塞的情况下，我们证明了脑血流（CBF）和较高皮质功能之间的定量关系。我们和其他人进一步证明了对颈动脉狭窄或接受内部切除术或颅外内脑（EC-IC）旁路治疗的患者的病例系列研究的认知改善。在我们提出的研究中，大约有294名患者将在随机分组时进行神经认知测试。然后在EC-IC旁路或COSS医疗部门的同等时间点发生30天，3个月和2年。所有患者将在3个月内进行后续PET扫描，以确定实际的OEF状态。调整由于COSS试验中的终点而导致的预期辍学，我们将具有80％的功率，以检测0.05的认知评分差异0.5 SD差异。认知评分与COSS残疾和生活质量措施的相关性将建立认知变化的临床相关性。除了对COSS试验的好处，如果可以证明再灌注手术可以改善认知，那么在其他颈动脉疾病治疗试验中，这项研究中的积极发现可能为使用类似的认知措施铺平了道路。