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.

随着新治疗方案的开发，乳腺癌患者的长期生存率不断提高，但其中 50-60% 的患者会出现化疗后认知障碍（PCCI），也称为“化疗脑”。多年来，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，PCCI 等神经系统后遗症给神经毒性化疗后的癌症幸存者带来了重大的健康负担，并且也具有重要的主权影响。我们面临着迫切需要探索临床相关的、创新的和有效的新治疗策略，长期目标是开发可以逆转 PCCI 并改善患者生活质量的靶向神经康复疗法。目前尚无基于证据的治疗方案。但初步研究发现，认知训练（CT）可以改善 PCCI 患者的认知能力。此外，非侵入性脑刺激（NIBS）是一种提高训练效果的方法，可以缩短训练时间，诱导转移。未经训练的功能，以及长期的经颅直流电刺激 (tDCS)（最广泛使用的 NIBS 技术）与 CT 相结合的效果令人鼓舞，显示出对改善健康老龄化患者的认知能力有好处，但对于痴呆或轻度认知障碍患者也有好处。尚未在 PCCI 患者中进行过检查，我们将在双盲随机对照 II 期临床试验中评估工作记忆功能多次 CT 联合 tDCS 干预是否可行，并产生显着的长期益处和转移效应。在患者中PCCI。所有患者将在左背外侧前额皮质上同时进行九次训练，其中一半的样本将在进行 CT 时接受阳极 tDCS，而另一半将在训练期间接受假刺激。因此，本试验将持续三周，每周进行三次训练，旨在评估使用 tDCS 治疗方案改善认知功能的干预措施的可行性和有效性（概念验证）。具体目标是 (1) 评估 PCCI 患者干预的可行性，(2) 收集第一批疗效数据，通过直接训练效果进行操作，转移到未经训练的领域，以及对认知和质量的长期影响。关于可行性和行为结果，本研究的目的是（3）为未来的验证性随机对照试验（RCT）提供规划和指导方案开发（包括功效分析）。 CT+tDCS 的疗效提高 PCCI 患者的认知功能。