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Acute Exercise Cardioprotection From Doxorubicin

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02006979
First Posted: December 10, 2013
Last Update Posted: November 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
British Columbia Cancer Agency
Information provided by (Responsible Party):
Kristin Campbell, University of British Columbia
  Purpose
In rodents, a single bout of exercise prior to injection of a chemotherapy agent used to treat breast cancer prevents or attenuates a number of markers of cardiac injury. This study will investigate whether this finding translates to human breast cancer patients. Participants scheduled to receive chemotherapy for breast cancer will be randomized to exercise or no exercise 24 hours prior to every chemotherapy treatment. The effect on cardiac function will be compared between groups noninvasively by echocardiography and electrocardiography and a venous blood draw at baseline before chemotherapy, after the first treatment and at the end of chemotherapy.

Condition Intervention Phase
Breast Cancer Other: exercise Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effects of Exercise Before Doxorubicin Chemotherapy on Cardiac Function

Resource links provided by NLM:


Further study details as provided by Kristin Campbell, University of British Columbia:

Primary Outcome Measures:
  • global longitudinal strain [ Time Frame: 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle ]

Secondary Outcome Measures:
  • NT-proBNP [ Time Frame: 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle ]
    biomarker of cardiac injury

  • signal-averaged ECG area ratio [ Time Frame: 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle ]

Enrollment: 24
Actual Study Start Date: January 15, 2016
Study Completion Date: May 25, 2016
Primary Completion Date: May 25, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exercise
an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post
Other: exercise
An acute bout of exercise performed 24 hours prior to every anthracycline infusion.
No Intervention: No exercise
no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines

  Hide Detailed Description

Detailed Description:
  1. Purpose The purpose of this study is to investigate whether performing a single bout of exercise 24 hours prior to receiving infusions of the anthracycline chemotherapy agent doxorubicin for breast cancer can prevent some of the damaging cardiac effects. Currently, doxorubicin is the most effective chemotherapy agent for breast cancer but is also the most damaging. As such, increased risk of cardiovascular disease is a growing concern in doxorubicin-treated patients. Current strategies for minimizing cardiac injury are dose reduction and discontinuation of therapy, which compromise the effectiveness of the treatment. Interventions that can minimize the cardiac injury associated with doxorubicin could reduce cancer-related and cardiovascular disease-related mortality in women diagnosed with breast cancer.
  2. Hypotheses 1. Performing an acute bout of exercise within 24 hours before anthracycline infusion will decrease the acute negative change in markers of cardiotoxicity after the first anthracycline infusion seen in those who do not exercise for 72 hours prior.

2. Performing exercise within 24 hours before every infusion of anthracycline will decrease the negative change in markers of cardiac dysfunction seen at the end of chemotherapy in those who do not exercise for 72 hours prior to each infusion.

3) Justification An acute exercise bout prior to induction of a myocardial infarction in animals provides cardioprotective benefit by reducing the size of the infarct relative to control animals. Recently, acute exercise performed 24 hours before anthracycline injection in rodents has also provided a cardioprotective benefit. Oxidative stress and apoptosis of cardiomyocyte mitochondria are primary mechanisms of anthracycline-induced cardiotoxicity. The single acute bout of exercise prevented or attenuated some of the anthracycline-induced negative effects on cardiomyocytes including oxidative stress, apoptosis, mitochondrial dysfunction, as well as systolic dysfunction. There are no studies to date that have investigated the cardiac effects of an acute bout of exercise in close proximity to anthracycline infusion in humans. Aerobic exercise training is recommended throughout chemotherapy treatment, but there are no guidelines in place in terms of the timing of exercise in relation to receipt of chemotherapy infusions.

4) Objectives

  1. To compare the acute effect of performing exercise (within 24 hours before the first infusion) compared to no exercise (no exercise for 72 hours prior to the first infusion) on markers of cardiotoxicity 24-48 hours after the first anthracycline infusion.
  2. To compare the chronic effect of performing exercise (within 24 hours before every infusion) compared to no exercise (no exercise for 72 hours prior to every infusion) on markers of cardiotoxicity 7 to 14 days after the final anthracycline infusion 5) Research Method This study will be a two-arm randomized control trial. Twenty-four women aged 18 or older newly diagnosed with stage I-IIIA breast cancer, and scheduled to receive neoadjuvant or adjuvant doxorubicin chemotherapy in cycles of 2-3 weeks will be recruited by oncologist referral and posters. Participants will be randomized to one of two conditions: i) an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 24-48 hours post; or ii) no exercise for 72 hours prior or 24-48 hours post each cycle of anthracyclines.

6) Statistical Analysis The primary outcome will be global longitudinal strain measured by echocardiography. The secondary outcomes will be the NT-proBNP cardiac biomarker measured with an assay of blood taken via venous blood draw, and the other cardiac strain parameters, as well as standard systolic and diastolic echocardiographic parameters. The exploratory outcome will be signal-averaged electrocardiography. Outcome measures will be performed at the following time points: 1) Post diagnosis and >24 hours prior to the first cycle of anthracyclines; 2) 24-48 hours after the first cycle; 3) at least one week after the last cycle of anthracyclines, but before subsequent chemotherapy treatments.

Baseline characteristics of the two groups will be compared with independent t-tests. Descriptive statistics and frequencies will be calculated for all continuous and categorical variables. The Shapiro-Wilk test will be used to test the assumption of normality for all continuous variables. Levene's test will be used to test the homogeneity of variance assumption. The acute effect will be determined by the difference between time points 1) and 2). The chronic effect will be determined by the difference between time points 1) and 3). For each analysis, a time by condition (2 x 2) repeated mixed model ANOVA will be performed. If the interaction effect is not statistically significant, the main effects of time and condition will be explored. An alpha of 0.05 will be used for all analyses. The required sample size is estimated to be 20 participants based on reported global longitudinal strain changes from prior to anthracyclines to post anthracyclines in breast cancer patients. To allow for a 20% dropout rate, 24 participants total will be recruited.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • newly diagnosed with stage I-IIIA breast cancer
  • scheduled to receive neoadjuvant or adjuvant doxorubicin chemotherapy in cycles of 2-3 weeks long
  • receive their oncologist's approval to exercise
  • be able to complete first time point of data collection prior to first chemotherapy cycle
  • be able to understand and provide written informed consent in English

Exclusion Criteria:

  • concurrent participation in a structured exercise program or study
  • have orthopedic limitations to exercise
  • pre-existing cardiovascular disease
  • uncontrolled hypertension (blood pressure ≥ 140/90 mmHg)
  • uncontrolled diabetes
  • respiratory disease
  • current smoking status
  Contacts and Locations
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): NCT02006979


Locations
Canada, British Columbia
University of British Columbia Breast Cancer Research Exercise Gym
Vancouver, British Columbia, Canada, V5Z 4C2
Sponsors and Collaborators
University of British Columbia
British Columbia Cancer Agency
Investigators
Principal Investigator: Kristin L Campbell, PhD University of British Columbia
  More Information

Responsible Party: Kristin Campbell, Dr. Kristin Campbell, University of British Columbia
ClinicalTrials.gov Identifier: NCT02006979     History of Changes
Other Study ID Numbers: H13-03090
First Submitted: December 5, 2013
First Posted: December 10, 2013
Last Update Posted: November 10, 2017
Last Verified: April 2017

Keywords provided by Kristin Campbell, University of British Columbia:
cardiotoxicity
Chemotherapy, Adjuvant
Breast Neoplasms
Exercise
Cardiotoxins
Echocardiography
Speckle tracking
Biological Markers
Electrocardiography

Additional relevant MeSH terms:
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action