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

• Applicant: Professorin Dr. Agnes Flöel
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Human Cognitive and Systems Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517737874

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.

• DFG Programme: Clinical Trials
• Co-Investigators: Dr. Daria Antonenko; Dr. Antje Kristina Belau; Professorin Dr. Eva-Lotta Brakemeier