Phase III Study of Donepezil in the Irradiated Brain

多奈哌齐在受辐射大脑中的 III 期研究

• 批准号: 7262840
• 负责人: STEPHEN R RAPP
• 金额: $ 36.7万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7262840
• 关键词: Acetylcholine; Acetylcholinesterase; Acetylcholinesterase Inhibitors; Adverse effects; Affect; Alzheimer' s Disease; Anger; Animals; Aricept; Astrocytes; Behavioral; Behavioral Symptoms; Brain; Brain Injuries; Brain Neoplasms; Breast; Cancer Patient; Cerebrum; Cholinergic Agents; Chronic; Clinical; Cognitive; Complex; Cranial Irradiation; Data; Dementia; Demyelinations; Depressed mood; Development; Diagnosis; Disseminated Malignant Neoplasm; Distress; Doctor of Philosophy; Endothelial Cells; Event; Fatigue; Future; Galantamine; Hippocampus (Brain); Image; Impaired cognition; Incidence; Injury; Label; Language; Learning; Long-Term Survivors; Lung; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Memory; Metabolism; Metastatic malignant neoplasm to brain; Microglia; Moods; Morbidity - disease rate; N-acetylaspartate; Neurobehavioral Manifestations; Neurocognitive; Neurologic Manifestations; Neurons; Newly Diagnosed; Normal tissue morphology; Oligodendroglia; Organ; Participant; Pathway interactions; Patients; Performance; Perfusion; Personal Satisfaction; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Physicians; Placebo Control; Placebos; Population; Prevention; Prevention strategy; Preventive Intervention; Quality of life; Radiation; Radiation Injuries; Radiation therapy; Randomized; Research; Research Personnel; Severities; Site; Structure; Survivors; Symptoms; Testing; Thinking; Time; Vascular Dementia; Week; base; brain cell; cell type; cholinergic; cholinergic neuron; cognitive function; donepezil; double-blind placebo controlled trial; esterase; esterase inhibitor; functional disability; improved; irradiation; neurochemistry; novel strategies; programs; prospective; response to injury; rivastigmine; tumor; white matter change

DESCRIPTION (provided by applicant): Cognitive impairment associated with primary or metastatic brain tumors and related treatments, including radiation therapy, occurs in a significant proportion of patients with 10% of patients developing progressive dementia, and 50% to 90% showing deficits when assessed with sensitive tests of cognitive function. About 20-40% of the >1,300,000 new cancer patients diagnosed in 2004 developed brain metastases (mets). At least 200,000 cancer patients/year receive whole brain irradiation (WBI) for brain mets, while 15,000 receive partial (P) or WBI for the treatment of a primary brain tumor. Clinically, patients frequently complain of a neurocognitive symptom cluster that includes difficulty remembering, organizing thoughts, and language fluency. This neurocognitive symptom cluster in turn is associated with significantly reduced quality of life and mood. Presently, there are very few available treatments for neurocognitive symptoms in patients who have received cranial irradiation; and no known preventive interventions exist. Administration of selective inhibitors of acetylcholinesterase like donepezil (Aricept) has proven effective in improving neurocognitive functioning and behavioral symptoms in patients with Alzheimer's disease. A recent prospective, open-label Phase 2 study of donepezil in long-term (>6 month) survivors of P/WBI conducted by this research team demonstrated a significant reduction in neurocognitive symptoms, as well as a significant improvement in mood, fatigue and quality of life. We hypothesize that the AChE inhibitor, donepezil, will lessen the neurocognitive symptom cluster and improve quality of life and mood in long-term survivors of brain irradiation. Thus we propose a 24-week, Phase III, randomized, double-blind, placebo-controlled trial of donepezil with 200 patients following partial or whole brain irradiation. The significance of this application is that it represents the first prospective controlled trial of donepezil (a well-tolerated drug with proven efficacy for reducing cognitive and functional impairment in Alzheimer's dementia) in survivors of partial or whole brain irradiation. RELEVANCE: This study will demonstrate whether a drug that helps dementia patients will also help to reduce cognitive impairment following brain radiation treatment for tumors. If successful the study will offer physicians a treatment for radiation-induced cognitive impairment which also may improve mood and quality of life.

描述（由申请人提供）：与原发性或转移性脑肿瘤或相关治疗有关的认知障碍（包括放射疗法）发生在很大一部分患者中，患者中有10％的患者患有进行性痴呆症，50％至90％的患者在用敏感功能的敏感测试评估时表现出赤字。在2004年诊断出的> 130万名新癌症患者中，约有20-40％发生了脑转移（MetS）。至少有200,000名癌症患者/年患有全脑辐照（WBI），而15,000例则接受部分（P）或WBI治疗原发性脑肿瘤。在临床上，患者经常抱怨神经认知症状簇，其中包括难以记住，组织思想和语言流利性。这种神经认知症状簇反过来又与生活质量和情绪大大降低有关。目前，在接受颅辐射的患者中，几乎没有可用的神经认知症状治疗方法。并且没有已知的预防干预措施。事实证明，乙酰胆碱酯酶（如多奈哌齐）的选择性抑制剂已被证明有效改善阿尔茨海默氏病患者的神经认知功能和行为症状。该研究团队进行的长期（> 6个月）的P/WBI幸存者对多奈代兹尔的最新前瞻性开放标签2阶段研究表明，神经认知症状的显着降低以及情绪，疲劳和生活质量的显着改善。我们假设ACHE抑制剂Donepezil将减少神经认知症状簇，并改善脑照射长期幸存者的生活质量和情绪。因此，我们提出了一项为期24周，III期，随机，双盲，安慰剂对照试验，在部分或全脑照射后，有200名患者。该应用的意义在于，它代表了多奈替齐（Donepezil）（一种具有良好耐受性的药物，具有降低阿尔茨海默氏痴呆症的认知和功能障碍的良好疗效）。相关性：这项研究将证明有助于痴呆症患者的药物是否还将有助于减少肿瘤脑辐射治疗后的认知障碍。如果成功，该研究将为医生提供辐射引起的认知障碍的治疗方法，这也可能改善情绪和生活质量。