Dual-task Training Effects on Cognition in Breast Cancer Survivors: the BRAINonFIT Study (BRAINonFIT).

Study Overview
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Brief Summary
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The goal of this interventional study is to assess the effects of either physical exercise program or combined with cognitive training (dual motor and cognitive training program) on breast cancer survivors. The main questions it aims to answer are: Analyze the effectiveness of a supervised dual-task training program or a physical exercise program on the executive functions of the participants. Evaluate the impact of both interventions on physical function, emotional aspects, and important biomarkers related to muscle-brain crosstalk. Participants will perform a 20-week supervised and controlled program, three times a week, along with weekly calorie and step challenges. Researchers will compare the dual-task training group, with the physical exercise group, and with a control group, which will perform the guideline recommendations of physical activity (non-supervised) to see how these intervention approaches can impact cognitive functions, physical functions, emotional aspects, and biomarkers related to muscle-brain crosstalk. Assessments will take place at three-time points: at baseline, after the intervention (20 weeks post-baseline) and after a 12-week follow-up period (32 weeks post-baseline).

Official Title
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Dual-task Training Effects on Cancer-related Cognitive Impairment and Muscle-brain Crosstalk Biomarkers in Breast Cancer Survivors: the BRAINonFIT Study

Conditions
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Breast Cancer Survivors, Cognitive Impairment, Executive Dysfunction

Intervention / Treatment
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* Behavioral: Exercise
* Behavioral: Dual-Task Training
* Behavioral: Health and Wellness


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with stage I-IIIA breast cancer Completed primary treatment, including surgery, radiotherapy and/or chemotherapy Scheduled to receive adjuvant endocrine therapy, or currently receiving adjuvant endocrine therapy Without functional limitations or other illnesses that condition and prevent them from practising intense physical exercise FACT-Cog questionnaire score ≥ 10th percentile considering age groups Fluency in Spanish (spoken and written) Exclusion Criteria: Undergoing radiotherapy and/or chemotherapy FACT-Cog questionnaire score ≤ 10th percentile considering age groups Congenital heart disease Chronic lung disease Severe psychiatric disorders History of substance abuse, or dependence (other than tobacco) Mood disorders require treatment (anxiety or depression) Relapses (2-3 months before the study start)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study has been designed as a randomised, controlled, longitudinal (20 weeks), three-arm, parallel study with a follow-up phase (12 weeks).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Intervention<br>This arm will receive a 5-month (20 weeks) supervised exercise program based on aerobic and resistance/strength training together with a weekly calorie or step challenge. | Behavioral: Exercise<br>* Participants will complete a 5-month exercise program structured in 4 blocks of 5 weeks. Three supervised and combined aerobic/strength exercise sessions each week will be performed together with an aerobic weekly challenge. Aerobic exercise will be performed for 20-30 minutes using a treadmill, bicycle, or circuit training at light to moderate intensities (40-75% of heart rate reserve) during the first two blocks; gradually achieving high intensity (>75% of HHR) in the last two blocks. Heart rate and the subjective perception of the exertion scale (6-20 Borg scale) will be monitored. Strength exercises will be started at light to moderate intensities (2 sets of 15-20 repetitions at 40-50% of repetition maximum), performed muscle actions at high intensities in the last two blocks (2 sets of 8-15 repetitions at 50-75% RM); using elastic bands, free weights, and weights gym exercises.<br>|
| Experimental: Dual Motor-Cognitive Intervention<br>This arm will receive a 5-month (20 weeks) supervised and simultaneous dual-task program based on aerobic, resistance, and cognitive stimulation training together with a weekly calorie or step challenge | Behavioral: Dual-Task Training<br>* Participants will complete the same four-block exercise program in terms of type, frequency, intensity, and volume of physical/motor training. Simultaneous with the progression of physical/motor training, the complexity of cognitive stimulation will be increased according to the performance of the participants. General dual-task training will be performed, which describes the use of a physical/motor intervention with different cognitive stimulations (memory, language, intelligence, attention, processing speed, calculation, inhibitory control) that are not specific to the methods to be used for their assessment.<br>|
| Active Comparator: Health and Wellness Intervention<br>This arm will receive a 5-month health and wellness program. | Behavioral: Health and Wellness<br>* Participants randomly assigned to the health and wellness group will be advised and re-educated to support and improve health aspects. Participants in this group will aim to achieve the physical activity recommendations, and in addition, they will receive bi-weekly emails and phone call coaching with tools to empower patients with knowledge about physical exercise, nutrition, and brain health guidelines. Following completion of the 5-month exercise program, this group will receive an exercise program for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Executive Function (Cognitive Flexibility and Processing Speed) | Trail Making Test A and B (minimum and maximum values, defined by the time in seconds, depend on the age- and education-normalised groups; higher scores mean worse results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibitory Control and Concentration | Stroop Color and Word test (minimum and maximum values, defined by the time in seconds, depend on the age- and education-normalised groups; higher scores mean worse results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Verbal Intelligence, Non-verbal Intelligence, Verbal memory, and Non-verbal Memory | Reynolds Intellectual Assessment Scale (Global index values range from ≤ 69 to ≥ 130, mean value of 100; higher scores mean better results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Learning Ability | Wechsler Memory Scale subtest word pairs (The subtest score range from 40 to 60, mean value of 100; higher scores mean better results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Perceived Cognitive Functions | Functional Assessment of Cancer Therapy: Cognition (FACT-Cog) (Total score ranges from 0 to 148; higher scores mean better results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Max. Oxygen Consumption | Modified Bruce Test (80% sub-max) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Muscular Strength of shoulder and knee extensors | Isokinetic dynamometer | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Range of Movement | Manual Goniometer | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV) | Spirometry (FEV/FVC ratio, represented in percentages) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Volume of physical activity | Accelerometer (Volume in minutes per week) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Intensity of Physical Activity | Accelerometer (Intensity in metabolic equivalents) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Weight and Height | Body Mass Index (weight and height will be combined to report BMI in kg/m^2) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Brain-Derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor 17 (FDF-17), Soluble Klotho (S-KL) | Concentration of these proteins in plasma by ELISA kit (Concentration of these proteins will be expressed in pg/mL or ng/mL) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Fatigue | Functional Assessment of Chronic Illness Therapy: Fatigue (FACIT-F) (Total score range from 0 to 52; higher scores mean better results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Pain Scale | Visual Analogue Scale (Total score ranges from 0 to 10; higher scores mean worse results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Depression | Back Depression Inventory (Total score ranges from 0 to 63; higher scores mean worse results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 
| Anxiety | State-Trait Anxiety Inventory (The score ranges from 20 to 80; higher scores mean worse results) | Baseline (week 0); Post-intervention (25 weeks post-baseline); and Post-follow up (32 weeks post-baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer-related Cognitive Impairment, Physical exercise, dual motor-cognitive tasks, cognitive stimulation, Neurocognitive disorders