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Exercise and Cognitive (Brain) Function in Breast Cancer Patients Getting Chemotherapy After Breast Surgery

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ClinicalTrials.gov Identifier: NCT04616300
Recruitment Status : Recruiting
First Posted : November 4, 2020
Last Update Posted : June 28, 2021
Sponsor:
Information provided by (Responsible Party):
Linda Trinh, University of Toronto

Brief Summary:
This study will primarily identify longitudinal associations between cardiorespiratory fitness (CRF) and cognitive function pre- (baseline) to post-chemotherapy (~3 months). This will be a prospective study of 50 BCS. We hypothesize that breast cancer patients undergoing chemotherapy who have higher levels of CRF at baseline will have significantly improved measures of attention, executive function, and memory post-chemotherapy. In addition, the exploratory aims will examine the longitudinal associations between physical activity (PA) and cognitive function from pre- to post-chemotherapy and explore the associations between inflammatory and non-inflammatory biomarkers and CRF with cognitive function.

Condition or disease
Breast Cancer

Detailed Description:

Cognitive impairments are reported as a chief quality of life (QoL) complaint by approximately 75% of breast cancer survivors (BCS). Women who have undergone adjuvant chemotherapy are at the highest risk for cognitive impairments, that may affect BCS up to 20 years post-treatment.Despite the prevalence and significance, it is largely underdiagnosed and there are no proven treatments beyond symptom management. Several studies have assessed cognitive function in cancer populations. Increasing evidence highlights the role of lifestyle behaviours on cancer-related outcomes, ranging from QoL to prognosis. However, very few studies have examined the associations of lifestyle factors and cognitive function in BCS.One of the most important mediators of CRCI in BCS may be cardiorespiratory fitness (CRF).

Our overall objective is to examine the behavioral and biological mechanisms that contribute to cognitive decline in BCS undergoing chemotherapy using an epidemiologic, prospective cohort design.

Assessments taken at baseline (pre-chemotherapy) and post-chemotherapy (month 3). Cognitive Function will be assessed using the NIH toolbox cognition battery. Physical Activity. PA will be assessed by accelerometers and through self-report using the Godin-Leisure Time Exercise Questionnaire. Cardiorespiratory Fitness will be assessed using the 6-minute walk test to estimate maximum oxygen uptake (VO2max).Cancer Biomarkers will be assessed using venous blood (2 microtubes) will be drawn from the antecubital vein by a trained phlebotomist. Biological markers analyzed in blood will include a multiplex panel of inflammatory cytokines (i.e., IL1, IL6, TNFα), and brain-derived neurotrophic factor (BDNF).

Our proposed study will be instrumental in designing future targeted translational lifestyle interventions to improve cognitive health in BCS. In addition, understanding the trajectory of cognitive function as it relates to these factors will determine the opportune timeframe to intervene during the cancer care continuum for the greatest impact

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 3 Months
Official Title: Cardiorespiratory Fitness, Inflammatory Biomarkers, and Cognitive Function Patterns During Treatment for Breast Cancer: A Prospective Cohort Study
Actual Study Start Date : December 12, 2019
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer




Primary Outcome Measures :
  1. Fluid Cognition (Composite) [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). This composite includes all the tests noted above that are fluid ability measures: Flanker, Dimensional Change Card Sort, Picture Sequence Memory, List Sorting and Pattern Comparison. This composite score is derived by averaging the normalized scores of each of the measures, and then deriving scale scores based on this new distribution. An Age-Adjusted Scale Score, Fully Adjusted Scale Score, Unadjusted Scale Score and Age-Adjusted National Percentile are provided for the Fluid Cognition Composite. The Fluid Cognition Composite is a more global assessment of individual and group fluid cognition functioning. Higher scores indicate higher levels of functioning.


Secondary Outcome Measures :
  1. Executive/Attention [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Flanker Inhibitory Control and Attention Test tests the ability to inhibit visual attention to irrelevant task dimensions. A scoring algorithm integrates accuracy and reaction time yielding scores from 0 to 10. There are 40 trials and the average time to complete the task is 4 minutes.To interpret individual performance, one can evaluate all three types of scale scores in which higher scores indicate higher levels of ability to attend to relevant stimuli and inhibit attention from irrelevant stimuli.

  2. Executive/Shifting [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Dimensional Change Card Sort Test involves a target visual stimulus that must be matched to 1 of 2 choice stimuli according to shape or color. Scoring is based on an algorithm that weights reaction time. A total of 40 trials require 4 minutes. Higher scores indicate higher levels of cognitive flexibility.

  3. Working Memory [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The List Sorting Working Memory Test includes a series of stimuli is presented on the computer screen visually (object) and orally (spoken name), 1 at a time. Participants are instructed to repeat the stimuli to the tester in order of size, from smallest to largest. The List Sorting task takes approximately 7 minutes to administer. Test scores consist of total items correct across all trials. Higher scores indicate better working memory.

  4. Episodic Memory [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Picture Sequence Memory Test involves a presentation of stimuli which are pictured objects and activities, thematically related but with no inherent order. For each trial, pictures appear in the center of the screen and then are moved 1 at a time into a fixed spatial order, as an audio file simultaneously describes the content of each. The score is based on the cumulative number of adjacent pairs of pictures remembered correctly over 3 learning trials. The test takes approximately 10 minutes. Higher scores indicate better episodic memory.

  5. Language [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Oral Reading Recognition Test measures the ability to pronounce single printed words and/or to recognize letters. Items are administered by computer adaptive testing (CAT) and participant responses are entered by the tester. The CAT item bank contains approximately 250 items with only 30 to 40 that will be presented, depending on performance. Average administration time is 4 minutes. A higher Computed Score for Reading would mean that the participant is able to correctly identify more difficult words on the subsequent assessment, which may indicate developmental growth or a return to a previous level of functioning.

  6. Language [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Picture Vocabulary Test involves single words that are presented via an audio file, paired simultaneously with 4 screen images of objects, actions, and/or depictions of concepts. The participant will pick the picture that matches the spoken word. Total administration time is approximately 5 minutes. To interpret individual performance, one can evaluate all three types of scale scores. A participant's age-adjusted scale score at or near 100 indicates vocabulary ability that is average for the age level. Scores around 115 suggest above-average vocabulary ability, while scores around 130 suggest superior ability - in the top 2 percent nationally for age, based on Toolbox normative data.

  7. Processing Speed [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Pattern Comparison Processing Speed Test requires participants to identify whether two visual patterns are the "same" or "not the same." Average time of administration is 3 minutes and the score is the number of correct items (of a possible 130) completed in 90 seconds. Higher scores indicate faster speed of processing.

  8. Crystallized Cognition [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). This composite includes the Picture Vocabulary and Reading Tests. This composite score is derived by averaging the normalized scores of each of the measures, and then deriving scale scores based on this 14 new distribution. An Age-Adjusted Scale Score, Fully Adjusted Scale Score, Unadjusted Scale Score and Age-Adjusted National Percentile are provided for the Crystallized Cognition Composite. Crystallized Cognition Composite is a more global assessment of individual and group verbal reasoning. Higher scores indicate higher levels of functioning.

  9. Immediate Recall [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Auditory Verbal Learning Test (Rey) measures immediate recall. Unrelated words presented via audio recording and participant recalls as many as possible. he Rey is scored by taking the sum of the number of words recalled across all trials (possible range is 0-45 words). The raw score is most commonly used for interpretation of the Rey test, with higher scores reflecting better episodic memory.

  10. Processing Speed [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Oral Symbol Digit Test measures speed of processing. Symbols on the screen are associated with a number, then presented with symbols without numbers. The Oral Symbol Digit Test is scored as the number of items answered correctly in 120 seconds (possible range is 0-144).Higher scores indicate better processing speed.

  11. Objectively-assessed physical activity [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Objectively assessed PA was measured using Actigraph GTX3+ accelerometers (Pensacola, FL). Participants will wear the accelerometer on their non-dominant hip during waking hours for 7 consecutive days. Data will be downloaded in 60-s epochs and processed and converted to mean counts per minute in ActiLife software package (Version 6; Actigraph) to estimate daily minutes of light (101-1951 counts min-1), moderate (1952-5724 counts min-1), vigorous (≥ 5725 counts min-1), and total moderate-to-vigorous physical activity (MVPA; ≥ 1952 counts min-1) based on established cut-points (Freedson, Melanson, & Sirard, 1998). Estimated average daily minutes spent in each activity intensity category was calculated by dividing the number of minutes spent in each category by the total number of valid days worn.

  12. Self-reported physical activity [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Physical activity will be assessed using a modified version of the validated leisure score index (LSI) from the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Participants are asked to recall the average number of times per week and average duration they performed light (minimal effort, no perspiration), moderate (not exhausting, light perspiration), and vigorous (heart beats rapidly, sweating) physical activity during free time in the past month. The percentage of participants meeting the public health aerobic physical activity guidelines was calculated based on the physical activity guidelines recommended for cancer survivors by the American College of Sports Medicine. These guidelines recommend that individuals obtain 75 min of vigorous aerobic physical activity per week, 150 min of moderate aerobic physical activity per week, or an equivalent combination. Thus, will calculated physical activity minutes as moderate minutes plus two times the vigorous minutes.

  13. Cancer biomarkers [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cancer Biomarkers will be assessed using venous blood (2 microtubes) will be drawn from the antecubital vein by a trained phlebotomist. Biological markers analyzed in blood will include a multiplex panel of inflammatory cytokines (i.e., IL1, IL6, TNFα), and brain-derived neurotrophic factor (BDNF).

  14. Cardiorespiratory fitness [ Time Frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3) ]
    Cardiorespiratory Fitness will be assessed using the six-minute walk test (6MWT) to estimate maximum oxygen uptake (VO2max).The 6MWT measures the distance in meters an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes at their own pace.A lower score (reflecting less distance covered) indicates worse function.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
50 BCS from the Odette Cancer Centre and breast cancer organizations within the Greater Toronto Area
Criteria

Inclusion Criteria:

  • 18-65 years old
  • histologically-confirmed stage I-III breast cancer, but prior to the initiation of chemotherapy (<1 cycle of adjuvant therapy or neoadjuvant therapy)
  • no diagnosed major cognitive disorders and uncontrolled comorbidities.

Exclusion Criteria:

  • received neoadjuvant chemotherapy and scheduled to receive adjuvant chemotherapy
  • scheduled to receive concurrent radiation therapy with chemotherapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04616300


Contacts
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Contact: Linda Trinh, PhD (416) 946-3624 linda.trinh@utoronto.ca

Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre -Odette Cancer Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Ellen Warner, MD         
Principal Investigator: Ellen Warner, MD         
Sponsors and Collaborators
University of Toronto
Publications:

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Responsible Party: Linda Trinh, Assistant Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT04616300    
Other Study ID Numbers: 38406
First Posted: November 4, 2020    Key Record Dates
Last Update Posted: June 28, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Linda Trinh, University of Toronto:
cardiorespiratory fitness
cognitive function
physical activity
chemotherapy treatment
cancer biomarkers
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases