Phase II clinical trial of transcranial direct current stimulation in the treatment of primary progressive aphasia

经颅直流电刺激治疗原发性进行性失语症II期临床试验

• 批准号: 10705285
• 负责人: Roy H Hamilton
• 金额: $ 134.91万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705285
• 关键词: Address; Affect; Aftercare; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Anomia; Aphasia; Area; Atrophic; Attention; BDNF gene; Behavioral; Biological; Brain; Brain imaging; Canada; Characteristics; Clinical; Clinical Research; Clinical Trials; Clinical effectiveness; Cognitive; Collaborations; Communication; Crossover Design; Degenerative Disorder; Disease; Double-Blind Method; Elderly; Failure; Frontotemporal Dementia; Genetic Polymorphism; Goals; Health Sciences; Image; Impairment; Inferior; International; Intervention; Investigation; Language; Language Disorders; Language Therapy; Left; Magnetic Resonance Imaging; Measures; Membrane Potentials; Multi-Institutional Clinical Trial; Names; Neurodegenerative Disorders; Neurologic; Neurons; North America; Oral; Outcome; Parietal; Participant; Patients; Pennsylvania; Performance; Persons; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Pilot Projects; Placebos; Population; Positioning Attribute; Prevalence; Primary Progressive Aphasia; Production; Progressive Nonfluent Aphasias; Publishing; Randomized; Research; Research Personnel; Rest; Risk; Severities; Site; Synaptic Transmission; Synaptic plasticity; Syndrome; Techniques; Testing; Therapeutic; Thick; Universities; Variant; Work; Writing; alternative treatment; arm; behavior test; bilingualism; clinical practice; clinical translation; cognitive control; cohort; computerized; effective therapy; experience; improved; neural; neuroimaging; neuroregulation; novel; novel therapeutics; patient population; prevent; primary outcome; remediation; response; sex; spelling; success; symptom treatment; targeted treatment; transcranial direct current stimulation

Primary progressive aphasia (PPA), a debilitating condition of language loss associated with Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) affecting many patients with frontotemporal dementia (FTD) and Alzheimer’s disease (AD), lacks effective treatments. One of the most common and burdensome impairments associated with this manifestation of AD/ADRD is anomia, the inability to access the names of objects, experienced by patients as word-finding difficulty. Transcranial direct current stimulation (tDCS), a form of noninvasive neuromodulation, shows promise as an intervention for anomia in persons with PPA. However, efforts to introduce this novel treatment approach into clinical practice are hampered by the modest size and scope of prior tDCS studies in this patient population, which prevents establishment of clear, robust clinical evidence to support the widespread use of tDCS in clinical contexts. To address this gap, this proposal aims to conduct the world’s first well-powered, multi-site Phase 2 clinical trial of tDCS therapy in PPA. In order to accomplish this goal, the current project solidifies a collaboration between research teams at Johns Hopkins, University of Pennsylvania, and Baycrest Health Sciences, which have collectively produced 100% of the published studies on tDCS in PPA in North America and 80% of the studies internationally. In a total cohort of 120 patients with PPA, we will employ a randomized, double-blind, within-subject, cross-over design similar to trials that have been previously employed at each of the contributing sites. Following baseline behavioral testing focused on language abilities and MRI imaging, subjects with PPA will receive 10 daily sessions over two weeks of either tDCS paired with NAming and SPelling treatment (NASP; a behavioral language therapy targeting both oral and written naming production) or sham (placebo) tDCS paired with NASP. Participants will undergo behavioral testing and imaging again at the end of the intervention, receive behavioral testing a month later, and then repeat testing and brain imaging 3 months after the end of the intervention. Participants will then switch study arms and receive the intervention, testing, and imaging at the same intervals. We will also conduct baseline behavioral testing and neuroimaging (with no treatment) on 60 neurologically healthy older adults for comparison to PPA subjects with respect to language performance and brain imaging. Subsequent analyses will determine whether tDCS over the left frontal language areas paired with naming treatment results in persistent improvement in oral and written naming, and will also identify the clinical, neural, biological, cognitive, and demographic characteristics that predict tDCS effects on naming performance. Owing to our unique opportunity to study a largely bilingual population in Canada, we will focus specific attention on bilingualism as a demographic feature that may influence outcomes. Overall, this impactful trial will provide the most reliable answer to date as to whether tDCS is effective for treating naming deficits in PPA and will help the field to identify patients best suited for this promising intervention in AD/ADRD.

初级进行性失语（PPA）是与阿尔茨海默氏病和阿尔茨海默氏病有关的语言丧失状况的使人衰弱的状况，影响了许多额叶痴呆症（FTD）和阿尔茨海默氏病（AD）（AD）（AD）的患者缺乏有效治疗方法。与AD/ADRD表现相关的最常见和抛光的障碍之一是异常，无法访问患者经历的物体名称，因为患者很难找到索引。经颅直流模拟（TDCS）是一种非侵入性神经调节的形式，在患有PPA的人中对异常症表示有望。但是，将这种新颖的治疗方法引入临床实践的努力受到该患者人群先前的TDCS研究的适度范围和范围的限制，这阻止了在临床环境中建立明确，可靠的临床证据以支持TDC的宽度。为了解决这一差距，该提案旨在进行世界上第一个在PPA中进行TDCS治疗的第2期临床试验。为了实现这一目标，目前的项目巩固了约翰·霍普金斯大学，宾夕法尼亚大学和Baycrest Health Sciences的研究团队之间的合作，这些研究团体在北美PPA和80％的研究中共同生产了100％关于TDCS的发表研究。在总共120名PPA患者中，我们将采用随机，双盲，受试者内部的，交叉设计类似于以前在每个贡献地点进行的试验。在集中在语言能力和MRI成像上的基线行为测试之后，患有PPA的受试者将在两周的TDC中接受10次每日疗程，并与命名和拼写治疗（NASP；一种针对口服和书面命名生产的行为语言疗法）或SHAMBO（plastbo）TDC与NASP配对的行为语言治疗。参与者将在干预结束时再次进行行为测试和成像，一个月后接受行为测试，然后在干预结束后3个月重复测试和大脑成像。然后，参与者将切换研究臂，并以相同的间隔接受干预，测试和成像。我们还将对60位神经系统健康的老年人进行基线行为测试和神经影像学（无治疗），以与PPA受试者相对于语言表现和大脑成像进行比较。随后的分析将确定左额语区域与命名治疗配对的TDC是否会导致口服和书面命名的持续改善，还将确定临床，神经元，生物学，认知和人口统计学特征，以预测TDCS对命名性能的影响。由于我们在加拿大研究主要双语人群的独特机会，我们将专门关注双语主义，这是一种可能影响结果的人群特征。总体而言，这项有影响力的试验将为迄今为止提供最可靠的答案，即TDC是否有效治疗PPA的命名防御，并将帮助该领域确定最适合这种承诺的AD/ADRD干预的患者。