RESET-BRAIN: REhabilitation of SleEp and CogniTive Impairment in BReast Cancer Survivors Using an App-based Intervention

The study is a randomized controlled trial comparing the effect of app-based cognitive behavioral therapy for insomnia (CBT-I) on cognitive function and insomnia to an active control group (sleep hygiene). Participants will be 84 breast cancer survivors who have completed primary treatment within 1-5 years and experience insomnia and cognitive impairment. After baseline assessment, participants will be randomized to either app-based CBT-I or sleep hygiene (active control). Both groups will undergo post-treatment assessments and 6-months follow-up assessments. The primary outcomes will be cognitive impairment assessed with the Conners Continuous Performance Test (CCPT) and insomnia assessed with the Insomnia Severity Index (ISI). To explore potential neurobiological and inflammatory mechanisms, structural magnetic resonance imaging (MRI) and inflammatory markers will be secondary outcomes. To provide a broader insight into cognitive function, participants will undergo further neuropsychological assessment with various standardized neuropsychological tests.

The study has the following aims and hypotheses:

PRIMARY AIM: To investigate whether an app-based CBT-I is associated with improved sleep and cognitive function in BC survivors screened for insomnia and CI when compared with an active control group. PRIMARY HYPOTHESIS: Compared with an active control group, CBT-I will be associated with a statistically significantly greater reduction in insomnia severity using the ISI and improvement of sustained attention and executive function assessed objectively using the CCPT. Effects on secondary sleep outcomes will also be tested. Exploratory hypothesis: Improvements in sustained attention and executive function will be mediated by improved insomnia severity and sleep outcomes.

SECONDARY AIM 1: To investigate whether CBT-I is associated with altered structural brain outcomes when compared with an active control group. HYPOTHESIS: Compared with an active control group, CBT-I will be associated with changes in brain gray and white matter properties, structural network topology, as well as glymphatic function as operationalized with the diffusion tensor image along the perivascular space (DTI-ALPS) approach.

SECONDARY AIM 2: To explore whether CBT-I is associated with changes in inflammatory immune function (IL-1β, IL-6, TNF-α, IFN-γ) when compared with an active control group. HYPOTHESIS: Compared with an active control group, CBT-I will be associated with a statistically significantly greater reduction in inflammatory markers. Improvements in sustained attention and executive function will be mediated by changes in inflammatory markers.

• Psychomotor Vigilance Test (PVT) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Trail-Making Test Part A (TMT-A) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) - Coding [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) - Digit span [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Paced Auditory Serial Addition Test (PASAT) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Hopkins Verbal Learning Test-Revised (HVLT-R) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Brief Visuospatial Memory Test-Revised (BVMT-R) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Controlled Oral Word Association Test (COWAT) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Trail-Making Test Part B (TMT-B) [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Stroop Color and Word Test [Срок оценки: Baseline (week 0), post-treatment (approximately week 9), 6-months follow-up (approximately week 33)]
• Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) - Information [Срок оценки: Baseline (week 0)]
• Glymphatic function [Срок оценки: Baseline (week 0), 6-months follow-up (approximately week 33)]