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.

原发性进行性失语症 (PPA) 是一种与阿尔茨海默病和阿尔茨海默病相关痴呆 (AD/ADRD) 相关的语言丧失性疾病，影响许多额颞叶痴呆 (FTD) 和阿尔茨海默病 (AD) 患者，目前缺乏有效的治疗方法之一。与 AD/ADRD 的这种表现相关的最常见和繁重的障碍是失忆症，即无法说出物体的名称，患者会经历经颅直接找词困难。电流刺激 (tDCS) 是一种无创神经调节形式，有望作为 PPA 患者贫血的干预措施，然而，将这种新颖的治疗方法引入临床实践的努力因先前 tDCS 研究的规模和范围有限而受到阻碍。患者群体，这阻碍了建立明确、有力的临床证据来支持 tDCS 在临床环境中的广泛使用。为了解决这一差距，该提案旨在开展世界上第一个功能强大的多站点 2 期临床试验。为了实现这一目标，当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，这些研究团队共同完成了 100% 的北部 PPA 中的 tDCS 已发表研究。美国和国际上 80% 的研究在总共 120 名 PPA 患者的队列中，我们将采用类似于以前采用的试验的随机、双盲、受试者内交叉设计。在以语言能力和 MRI 成像为重点的基线行为测试之后，患有 PPA 的受试者将在两周内每天接受 10 次 tDCS 治疗，并配合 NAming 和 Spelling 治疗（NASP；一种针对口语和口语的行为语言治疗）。书面命名生产）或假（安慰剂）tDCS 与 NASP 配对，参与者将在干预结束时再次接受行为测试和成像，一个月后接受行为测试，然后在干预结束后 3 个月重复测试和脑成像。然后，参与者将切换研究组并以相同的时间间隔接受干预、测试和成像。我们还将对 60 名神经健康的老年人进行基线行为测试和神经影像学检查（不进行治疗），以便与 PPA 受试者进行比较。随后的分析将确定左额叶语言区域的 tDCS 与命名治疗相结合是否会导致口头和书面命名的持续改善，并且还将确定临床、神经、生物、认知和人口特征。预测 tDCS 对命名的影响由于我们有独特的机会研究加拿大大部分双语人群，我们将特别关注双语作为可能影响结果的人口特征。总体而言，这项有影响力的试验将为 tDCS 是否有效提供迄今为止最可靠的答案。可以有效治疗 PPA 中的命名缺陷，并将帮助该领域识别出最适合这种有希望的 AD/ADRD 干预措施的患者。