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.

随着新治疗选择的发展，乳腺癌患者的长期存活率正在增加。但是，这些患者中有50％的患者经历了化学疗法后认知障碍（PCCI），也称为“化学邻晶”。 PCCI可以持续多年，并发生在各种认知领域，例如执行功能，记忆，处理速度和注意力。神经后遗症（例如PCCI）在神经毒性化疗后为癌症幸存者提供了严重的健康燃烧，并且也具有重要的社会经济影响。这是我们面临的紧迫需要探索临床上相关，创新和有效的新治疗策略，其长期目标是开发有针对性的神经保障疗法，这可以逆转PCCI并改善患者的生活质量。没有循证治疗方案可用，但是第一项研究发现了初步证据表明认知训练（CT）可以提高PCCI患者的认知能力。此外，非侵入性大脑刺激（NIB）是一种提高训练增益的方法，可以较短的训练期，将转移到未经训练的功能以及长期影响。结合经颅直流电流刺激（TDC）的有希望的结果是，使用CT最广泛的NIBS技术已显示出在健康衰老中改善认知性能的好处，并且在患有痴呆症或轻度认知障碍的患者中也显示出好处。 PCCI患者尚未检查此技术。我们将在双盲随机对照期II期临床试验中评估是否可行，如果工作记忆函数的组合CT可行，则可以对PCCI患者产生实质性的长期益处和转移效应。所有患者将在9次培训课程中完成CT，并在左下角前额叶皮层上同时使用高清阳极TDC。在执行CT时，一半的样品将接受阳极TDC，而另一半将在训练过程中进行假刺激。干预措施将持续三周，每周进行三场培训。因此，本试验旨在评估使用TDCS治疗方案作为CT的增强，以评估改善认知功能的干预措施的可行性和有效性（概念证明）。具体目的是（1）评估PCCI患者的干预措施的可行性，（2）收集第一个有效性数据，通过直接训练效应，转移到未训练的领域进行操作以及对多个时间点的认知和生活质量的长期影响。关于可行性和行为结局，本研究的目的是（3）与未来有关的计划和指导方案开发（包括功率分析），确认的随机对照试验（RCT）对CT-Plus-TDC在增加PCCI患者认知功能方面的有效性。