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: 10522254
• 负责人: Roy H Hamilton
• 金额: $ 150.09万
• 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/10522254
• 关键词: Address; Affect; Aftercare; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; Anomia; Aphasia; Area; Atrophic; Attention; BDNF gene; Behavioral; Biological; Brain; Brain imaging; Canada; Characteristics; Clinical; Clinical Research; 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; Phase III Clinical Trials; Pilot Projects; Placebos; Population; Positioning Attribute; Prevalence; Primary Progressive Aphasia; Production; Publishing; Randomized; Research; Research Personnel; Rest; Risk; Severities; Site; Synaptic Transmission; Synaptic plasticity; Syndrome; Techniques; Testing; Therapeutic; Thick; Universities; Variant; Work; alternative treatment; arm; base; behavior test; bilingualism; clinical practice; cognitive control; cohort; computerized; effective therapy; experience; improved; neuroimaging; neuroregulation; novel; novel therapeutics; patient population; prevent; primary outcome; relating to nervous system; response; sex; spelling; success; symptom treatment; targeted treatment

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。与 AD/ADRD 的这种表现相关的最常见和最繁重的障碍之一是失忆症，即无法说出物体的名称，患者会经历找词困难。经颅直流电刺激 (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，将这种新型治疗方法引入临床实践的努力受到了该患者群体先前 tDCS 研究规模和范围有限的阻碍，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。为了弥补这一差距，该提案旨在开展世界上第一个针对 PPA 的 tDCS 疗法的强有力的多中心 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北美已发表的 PPA tDCS 研究的 100% 和国际上 80% 的研究。在总共 120 名 PPA 患者的队列中，我们将采用随机、双盲、受试者内交叉设计，类似于之前在每个贡献站点采用的试验。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 配合 NAming 和 Spelling 治疗（NASP；一种针对口头和书面命名产生的行为语言治疗）或假（安慰剂）tDCS 配合 NASP。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检查（不进行治疗），以便与 PPA 受试者在语言表现和脑成像方面进行比较。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，并且还将确定预测 tDCS 对命名表现影响的临床、神经、生物、认知和人口特征。由于我们有独特的机会研究加拿大大部分双语人口，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 是否有效治疗 PPA 命名缺陷提供迄今为止最可靠的答案，并将帮助该领域确定最适合这种有希望的 AD/ADRD 干预措施的患者。