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

基本信息

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
项目类别：
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&apos 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

项目摘要

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和相关治疗（包括放射治疗）相关的认知障碍发生在相当大比例的患者中，其中 10% 的患者出现进行性痴呆，50% 至 90% 的患者在评估时表现出缺陷通过敏感的认知功能测试。 2004 年诊断的超过 1,300,000 名新癌症患者中，约有 20-40% 出现脑转移 (mets)。每年至少有 200,000 名癌症患者接受全脑照射 (WBI) 治疗脑转移，而 15,000 名癌症患者接受部分 (P) 或 WBI 治疗原发性脑肿瘤。临床上，患者经常抱怨神经认知症状群，包括记忆困难、思维组织困难和语言流畅性困难。这种神经认知症状群反过来又与生活质量和情绪的显着下降有关。目前，对于接受颅脑照射的患者的神经认知症状，可用的治疗方法很少；并且不存在已知的预防性干预措施。事实证明，服用选择性乙酰胆碱酯酶抑制剂如多奈哌齐（Aricept）可有效改善阿尔茨海默病患者的神经认知功能和行为症状。该研究小组最近在 P/WBI 长期（>6 个月）幸存者中进行的一项前瞻性、开放标签 2 期研究表明，多奈哌齐可显着减轻神经认知症状，并显着改善情绪、疲劳和生活质量。我们假设乙酰胆碱酯酶抑制剂多奈哌齐将减轻脑辐射长期幸存者的神经认知症状群并改善生活质量和情绪。因此，我们建议对 200 名接受部分或全脑照射的患者进行为期 24 周的 III 期随机、双盲、安慰剂对照试验。这项申请的意义在于，它代表了在部分或全脑辐射幸存者中进行的第一个多奈哌齐（一种耐受性良好的药物，已被证明可有效减少阿尔茨海默氏痴呆症认知和功能障碍）的前瞻性对照试验。相关性：这项研究将证明一种帮助痴呆症患者的药物是否也有助于减少肿瘤脑放射治疗后的认知障碍。如果成功，这项研究将为医生提供治疗辐射引起的认知障碍的方法，这也可能改善情绪和生活质量。