Neuromodulation through brain stimulation-assisted cognitive training in patients with post-chemotherapy cognitive impairment (Neuromod-PCCI): an explorative proof-of-concept randomized sham-controlled double-blind feasibility phase II trial

通过脑刺激辅助认知训练对化疗后认知障碍患者进行神经调节 (Neuromod-PCCI)：一项探索性概念验证随机假手术对照双盲可行性 II 期试验

• 批准号: 517737874
• 负责人: Professorin Dr. Agnes Flöel
• 金额: --
• 依托单位: Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/517737874?language=en
• 关键词: Neuromodulation; through; brain; stimulation; assisted

With the development of new treatment options, long-term survival rates of breast cancer patients are increasing. However, 50-60 % of these patients experience post-chemotherapy cognitive impairment (PCCI), also referred to as “chemobrain”. PCCI can persist for many years and occurs in various cognitive domains, such as executive functions, memory, processing speed, and attention. Neurological sequelae such as PCCI present a major health burden for cancer survivors following a neurotoxic chemotherapy, and also have important socioeconomic impact. Thus, we are faced with the pressing need to explore clinically relevant, innovative and effective new treatment strategies with the long-range aim of developing targeted neuro-rehabilitative therapy which can reverse PCCI and improve quality of life of the patients. No evidence-based treatment options are available, but first studies have found preliminary evidence that cognitive training (CT) may improve cognitive abilities of patients with PCCI. In addition, non-invasive brain stimulation (NIBS), an approach to boost training gains, allows for shorter training periods, induction of transfer to untrained functions, and long-term effects. Promising results of combining transcranial direct current stimulation (tDCS), the most widely used NIBS technique, with CT, have shown benefit for improving cognitive performance in healthy aging, but also in patients with dementia or mild cognitive impairment. This technique has not yet been examined in patients with PCCI. We will assess in a double-blind randomized controlled phase II clinical trial if a combined multi-session CT of working memory functions-plus-tDCS intervention is feasible and yields substantial long-term benefits and transfer effects in patients with PCCI. All patients will complete CT over nine training sessions with concurrent high-definition anodal tDCS over left dorsolateral prefrontal cortex. Half of the sample will receive anodal tDCS while performing the CT, whereas the other half will undergo sham stimulation during training. The intervention will span three weeks, with three training sessions per week. The present trial thus aims to assess the feasibility and efficacy (proof-of-concept) of an intervention for improving cognitive function using a tDCS treatment protocol as augmentation to CT. Specific aims are to (1) assess feasibility of the intervention for patients with PCCI, (2) collect first efficacy data, operationalized by direct training effects, transfer to untrained domains, and long-term effects on cognition and quality of life at multiple time points. With regard to both feasibility and behavioral outcomes, the purpose of the present study is to (3) inform planning and guide protocol development (including power analysis) in relation to future, confirmatory randomized controlled trials (RCT) on the efficacy of CT-plus-tDCS in increasing cognitive functions in patients with PCCI.

随着新的治疗方案的发展，乳腺癌患者的长期存活率正在上升。然而，这些患者中有50%-60%经历了化疗后认知障碍(PCCI)，也被称为“化疗障碍”。PCCI可以持续多年，发生在执行功能、记忆、加工速度和注意力等多个认知领域。PCCI等神经后遗症是神经毒性化疗后癌症幸存者的主要健康负担，也有重要的社会经济影响。因此，我们迫切需要探索具有临床意义、创新和有效的新的治疗策略，以发展具有针对性的神经康复治疗，从而逆转PCCI，提高患者的生活质量。目前尚无循证治疗方案，但初步研究发现，认知训练(CT)可能会改善PCCI患者的认知能力。此外，非侵入性脑刺激(NIB)是一种提高训练收益的方法，允许较短的训练时间，诱导转移到未训练的功能，并产生长期效果。将最广泛使用的NIBS技术经颅直流电刺激(Tdcs)与CT相结合的可喜结果显示，在健康老龄化以及痴呆症或轻度认知障碍患者中，经颅直流电刺激(Tdcs)有助于改善认知能力。这项技术还没有在PCCI患者中进行检验。我们将在一项双盲、随机对照的II期临床试验中评估工作记忆功能的多时段CT联合tDCS干预是否可行，并在PCCI患者中产生实质性的长期益处和转移效果。所有患者都将在9个训练课程中完成CT扫描，同时在左侧前额叶背外侧皮质上进行高清晰度阳极TDC扫描。一半的样本将在进行CT时接受阳极tDCs，而另一半的样本将在训练期间接受假刺激。干预将持续三周，每周三次培训。因此，本试验旨在评估使用tdcs治疗方案作为CT的补充来改善认知功能的干预的可行性和有效性(概念验证)。具体目的是：(1)评估PCCI患者干预的可行性；(2)收集通过直接训练效应进行操作的第一次疗效数据，转移到未训练领域，以及在多个时间点对认知和生活质量的长期影响。就可行性和行为结果而言，本研究的目的是(3)就CT-Plus-tDCs在改善PCCI患者认知功能方面的有效性进行规划并指导未来的验证性随机对照试验(RCT)的方案制定(包括功率分析)。