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Breast CancerNCT04616300

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

An observational study of Breast Cancer, run by University of Toronto at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years, women only
Conditions the study is for
Breast Cancer
How many people
50 participants
Where
1 siteCanada
Study dates
12 Dec 2019to 30 Apr 2025
How long will I take part?
3 Months
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Study population: 50 BCS from the Odette Cancer Centre and breast cancer organizations within the Greater Toronto Area

Who may be able to join

  • 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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Canada1 site, 1 recruiting
  • Sunnybrook Health Sciences Centre-Odette Cancer Centre

    Toronto, Ontario, M4N3M5

    Ellen Warner, MD

    Recruiting

Other trials in Canada

About this study

Official title: Cardiorespiratory Fitness, Inflammatory Biomarkers, and Cognitive Function Patterns During Treatment for Breast Cancer: a Prospective Cohort Study

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.

Read the detailed description

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.

Conditions
Breast Cancer
Keywords
cardiorespiratory fitness, cognitive function, physical activity, chemotherapy treatment, cancer biomarkers
Medical subject headings
Breast Neoplasms, Motor Activity

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fluid Cognition (Composite)

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

Secondary outcomes (14)
  1. Executive/Attention

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  2. Executive/Shifting

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  3. Working Memory

    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.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 match

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  4. Episodic Memory

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  5. Language (oral reading)

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  6. Language (picture vocabulary)

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  7. Processing Speed (Pattern comparison)

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  8. Crystallized Cognition

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  9. Immediate Recall

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  10. Processing Speed (oral symbol digit test)

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  11. Objectively-assessed physical activity

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  12. Self-reported physical activity

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  13. Cancer biomarkers

    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).

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

  14. Cardiorespiratory fitness

    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.

    Measured: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2020
  2. Study start12 Dec 2019
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion30 Apr 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
50 participants (estimated)
Target duration
3 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT04616300
Sponsor's protocol ID
38406
Status last verified
Dec 2024
First submitted
2 Nov 2020
Last updated
6 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004 Oct;26(7):955-69. doi: 10.1080/13803390490510905.

    PubMed 15742545
  • Kesler SR, Kent JS, O'Hara R. Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol. 2011 Nov;68(11):1447-53. doi: 10.1001/archneurol.2011.245.

    PubMed 22084128
  • Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol. 2012 Apr 1;30(10):1080-6. doi: 10.1200/JCO.2011.37.0189. Epub 2012 Feb 27.

    PubMed 22370315
  • Kesler S, Hadi Hosseini SM, Heckler C, Janelsins M, Palesh O, Mustian K, Morrow G. Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors. Clin Breast Cancer. 2013 Aug;13(4):299-306. doi: 10.1016/j.clbc.2013.02.004. Epub 2013 May 4.

    PubMed 23647804
  • Von Ah D, Tallman EF. Perceived cognitive function in breast cancer survivors: evaluating relationships with objective cognitive performance and other symptoms using the functional assessment of cancer therapy-cognitive function instrument. J Pain Symptom Manage. 2015 Apr;49(4):697-706. doi: 10.1016/j.jpainsymman.2014.08.012. Epub 2014 Sep 18.

    PubMed 25240787
  • Frank JS, Vance DE, Triebel KL, Meneses KM. Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy. J Neurosci Nurs. 2015 Dec;47(6):302-12. doi: 10.1097/JNN.0000000000000171.

    PubMed 26447567
  • Von Ah D, Habermann B, Carpenter JS, Schneider BL. Impact of perceived cognitive impairment in breast cancer survivors. Eur J Oncol Nurs. 2013 Apr;17(2):236-41. doi: 10.1016/j.ejon.2012.06.002. Epub 2012 Aug 14.

    PubMed 22901546
  • Argyriou AA, Assimakopoulos K, Iconomou G, Giannakopoulou F, Kalofonos HP. Either called "chemobrain" or "chemofog," the long-term chemotherapy-induced cognitive decline in cancer survivors is real. J Pain Symptom Manage. 2011 Jan;41(1):126-39. doi: 10.1016/j.jpainsymman.2010.04.021. Epub 2010 Sep 15.

    PubMed 20832978
  • Jean-Pierre P, Johnson-Greene D, Burish TG. Neuropsychological care and rehabilitation of cancer patients with chemobrain: strategies for evaluation and intervention development. Support Care Cancer. 2014 Aug;22(8):2251-60. doi: 10.1007/s00520-014-2162-y. Epub 2014 Mar 27.

    PubMed 24671433
  • Zimmer P, Baumann FT, Oberste M, Wright P, Garthe A, Schenk A, Elter T, Galvao DA, Bloch W, Hubner ST, Wolf F. Effects of Exercise Interventions and Physical Activity Behavior on Cancer Related Cognitive Impairments: A Systematic Review. Biomed Res Int. 2016;2016:1820954. doi: 10.1155/2016/1820954. Epub 2016 Apr 10.

    PubMed 27144158
  • Wefel JS, Schagen SB. Chemotherapy-related cognitive dysfunction. Curr Neurol Neurosci Rep. 2012 Jun;12(3):267-75. doi: 10.1007/s11910-012-0264-9.

    PubMed 22453825
  • Ballard-Barbash R, Friedenreich CM, Courneya KS, Siddiqi SM, McTiernan A, Alfano CM. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012 Jun 6;104(11):815-40. doi: 10.1093/jnci/djs207. Epub 2012 May 8.

    PubMed 22570317
  • Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Al-Delaimy WK, Thomson CA, Kealey S, Hajek R, Parker BA, Newman VA, Caan B, Rock CL. Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol. 2007 Jun 10;25(17):2345-51. doi: 10.1200/JCO.2006.08.6819.

    PubMed 17557947
  • Zuniga KE, Mackenzie MJ, Roberts SA, Raine LB, Hillman CH, Kramer AF, McAuley E. Relationship between fruit and vegetable intake and interference control in breast cancer survivors. Eur J Nutr. 2016 Jun;55(4):1555-62. doi: 10.1007/s00394-015-0973-3. Epub 2015 Jun 30.

    PubMed 26123915
  • Jones LW, Haykowsky MJ, Swartz JJ, Douglas PS, Mackey JR. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007 Oct 9;50(15):1435-41. doi: 10.1016/j.jacc.2007.06.037. Epub 2007 Sep 24.

    PubMed 17919562

Questions about this trial

What is this clinical trial studying?

An observational study of Breast Cancer, run by University of Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Linda Trinh, PhD ((416) 946-3624, linda.trinh@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fluid Cognition (Composite) (time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04616300, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2024.

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