Cognitive Stimulation and Chemobrain. An Innovative Intervention for Cancer Survivors

Study Overview
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Brief Summary
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The present study aims to establish a non-pharmacological alternative in alleviating cognitive deterioration derived from undergoing chemotherapy treatment. Thus, the effectiveness of a personalized and computerized cognitive stimulation program in breast cancer survivors is assessed.

Detailed Description
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A phase I/II/III clinical trial is proposed in which the first two phases will serve to evaluate the safety of the intervention and the maximum tolerated time of computerized cognitive training per session in the absence of adverse effects. The third phase will consist of a double-blind randomized controlled trial where the effectiveness of the personalized and self-administered computerized cognitive stimulation program will be evaluated. Phase I. Based on a dose-escalation 3+3 design, experienced fatigue or adverse effects will be measured after succeeding 15 minutes cognitive stimulation training blocks. The training dose will be set to a block before extreme fatigue or notable adverse effect has been reported by two or more participants. A trained psychologist will supervise the process. Phase II. To evaluate the effectiveness of the intervention, 20 participants will undertake an interspersed training day and evaluation day through 15 consecutive days. In this way, a total of 8 evaluation sessions (day 1, 3, 5, 7, 9, 11, 13, and 15) and 7 cognitive stimulation sessions (day 2, 4, 6, 8, 10, 12, and 14) will be carried out. A trained psychologist will supervise every step of the process. Phase III. An 8-week personalized and computerized cognitive stimulation program will be established, where the training time per session will be as determined on phase I. 120 participants will be randomized 1:1 ratio to an intervention or active control group. All participants will undertake a pre and post-test, with a total of 40 training sessions (Monday to Friday) during 8 weeks. Although this phase is set to be an online home-based stage, the responsible psychologist will be monitoring participants' performance and will periodically contact participants via telephone.

Official Title
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Cognitive Stimulation Intervention Program for Cancer Survivors and Its Benefit on Cognitive Performance and Quality of Life

Conditions
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Breast Cancer, Cognitive Decline

Intervention / Treatment
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* Other: Personalized cognitive stimulation
* Other: Sham cognitive stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have been diagnosed with breast cancer. Having undergone chemotherapy. Report objective or subjective complaints of cognitive impairment. Exclusion Criteria: Metastases or brain tumors. Existence of a relevant medical, psychiatric, or neurological disorder. Significant visual or motor impairments. History of alcohol or drug abuse or dependence. Be receiving another cognitive stimulation intervention.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: A home-based intervention will be set through the CogniFit® online platform. Participants will access remotely from home using a personal computer or smart device. The cognitive stimulation program will be held for 5 consecutive days (Monday to Friday) for 8 weeks, completing a total of 40 training sessions. Researchers will supervise the participant's performance daily and will periodically contact participants via telephone.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Online games designed to target specific cognitive skills such as attention, perception, or inhibition). Activities' difficulty will be automatically adjusted accordingly to each participant's performance, always demanding a maximum cognitive effort. | Other: Personalized cognitive stimulation<br>* Online gamified activities designed to stimulate cognitive functions (specifically executive function) will be carried out through a mobile application or web browser. Performance feedback will be shown after each activity.<br>* Other names: CogniFit's personalized brain training;|
| Active Comparator: Control Group<br>Online painting and artistic games designed not to target the specific cognitive skills at test. Activities' duration will match those of the experimental group, and its difficulty will be constant through the intervention. | Other: Sham cognitive stimulation<br>* Non-therapeutic online games based on artistic tasks designed to not train the specific cognitive abilities at test. The time of each session will match that of the experimental group. Performance feedback will be shown after each game.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in mini-Mental Adjustment to Cancer Scale (mini-MAC) at Week 8 | The mini-MAC is a validated 29-item self-rated questionnaire that examines five cancer-specific coping strategies: fighting spirit, helplessness, anxious preoccupation, cognitive avoidance, and fatalism. Each item is scored using a 4-point Likert scale. Higher scores on each subscale mean greater use of that strategy. | Baseline and Week 8 | 
| Change from Baseline in Cognitive Assessment for Chemo Fog Research (CAB-CF) at Week 8 | The CAB-CF is an online neuropsychological assessment battery that evaluates a total of 23 cognitive skills, grouped into 5 cognitive domains (attention, memory, coordination, perception, and reasoning). Each cognitive skill is scored from 0 to 800. The cognitive domain score is calculated by averaging the scores of the cognitive skills that comprise it. Higher scores mean better cognitive performance. | Baseline and Week 8 | 
| Change from Baseline in the Functionality Assessment Instrument in Cancer Treatment - Cognitive Function (FACT-COG) at Week 8 | The FACT-COG is a 37 item self-report questionnaire that assesses patients' perception of their cognitive abilities, functionality, and quality of life. Each item is scored using a 5-point Likert scale. Higher scores indicate less perceived cognitive impairment. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the State-Trait Anxiety Inventory (STAI) at Week 8 | The STAI is a validated self-report that assesses anxiety that measures both trait and state anxiety. Each item is scored using a 4-point Likert scale. Possible scores range from 0 (no anxiety) to 60 (severe anxiety), for each category. | Baseline and Week 8 | 
| Change from Baseline in the Beck Depression Inventory (BDI-II) at Week 8 | The BDI-II is a validated 21-item self-report inventory designed to measure the frequency and severity of depressive symptoms. Scores range from 0 (no depressive symptoms) to 63 (severe depression). | Baseline and Week 8 | 
| Change from Baseline in the Brief Fatigue Inventory (BFI) at Week 8 | The BFI is a 9-items instrument designed to assess the severity and impact of cancer-related fatigue. For the three items that assess fatigue severity, scores range from 0 (no fatigue) to 10 (the worst fatigue you can imagine). For the six items that assess how fatigue interferes with daily life, scores range from 0 (does not interfere) to 10 (interferes completely). | Baseline and Week 8 | 
| Change from Baseline in the Measuring Quality of Life | The World Health Organization - abridged version (WHOQOL-BREF) at Week 8 | The WHOQOL-BREF is a 26-question questionnaire designed to measure the quality of life. It has two questions concerning the general satisfaction with health, and the remaining 24 questions are grouped in four areas: physical health, psychological health, social relations, and environment. Scores for each domain range from 0 (poor perceived quality of life) to 100 (greater perceived quality of life) | Baseline and Week 8 | 
| Change from Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) at Week 8 | The C-SSRS is a questionnaire designed to assess the existence of thoughts, desires or behaviors related to suicidal ideation, assessing a total of ten categories (wish to be dead; non-specific active suicidal thoughts; active suicidal ideation with any methods without intent to act; active suicidal ideation with some intent to act, without a specific plan; active suicidal Ideation with a specific plan and intent; preparatory acts or behavior; aborted attempt; interrupted attempt; actual attempt; completed suicide. The questionnaire can be administered as a self-report, with additional open-ended follow-up questions to provide more information. Scoring refers to the presence or absence of each of the 10 categories, provided by the dichotomous responses (Yes/No). | Baseline and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Cancer survivors, Chemobrain, Cognitive stimulation, Online intervention