ClinicalTrials.gov
ClinicalTrials.gov Menu

Caloric Restriction and Exercise for Protection From Anthracycline Toxic Effects (CREATE)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03131024
Recruitment Status : Recruiting
First Posted : April 27, 2017
Last Update Posted : August 22, 2018
Sponsor:
Collaborator:
Susan G. Komen Breast Cancer Foundation
Information provided by (Responsible Party):
University of Alberta

Brief Summary:
Doxorubicin and epirubicin are part of the class of chemotherapy agents called anthracyclines that are commonly used to treat breast cancer. Although these treatments work well against the tumor, they are known to cause damage to the heart muscle, resulting in diminished heart function that can be permanent, and may also damage the blood vessels and skeletal muscles. The purpose of this study is to determine whether short-term application of these interventions with specific timing relative to the receipt of each treatment can prevent the negative effects of anthracycline treatment on the heart, aorta (largest artery leaving the heart), and skeletal muscle, and reduce treatment symptoms. Fifty-six early stage breast cancer patients who will receive anthracycline treatment will be randomly assigned to 1 of 3 groups who will: 1) perform a single 30-minute aerobic exercise session 24 hours prior to each treatment; 2) eat a diet consisting of 50% less calories for 48 hours prior to each treatment; or 3) receive usual cancer care. Magnetic resonance imaging (MRI) will be used to precisely measure the function of the heart, aorta, and the lower leg skeletal muscle at rest, and again during exercise to allow detection of more subtle signs of damage. We will also measure exercise capacity (i.e. aerobic fitness), microscopic damage to the heart muscle cells, a marker released into the blood in response to anthracycline-related heart damage, tumor size in patients receiving chemotherapy before surgery, quality of life and fatigue. These measures will be performed before treatment, at the end of treatment and 1 year later.

Condition or disease Intervention/treatment Phase
Breast Cancer Female Dietary Supplement: 50% caloric restriction Other: Aerobic exercise Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: The Effects of Short-term Exercise or Caloric Restriction on Anthracycline Chemotherapy-related Treatment Toxicity
Actual Study Start Date : October 15, 2017
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : June 14, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Aerobic exercise
The exercise arm includes a single bout of supervised treadmill walking scheduled such that it would end approximately 24 hours prior to each of the participant's scheduled anthracycline treatment time.
Other: Aerobic exercise
The supervised exercise session will consist of a 10-minute warm-up, 30 minutes performed at 70-75% of heart rate reserve, which corresponds to a vigorous intensity, followed by a 5-minute cool-down

Experimental: 50% caloric restriction
The caloric restriction arm will restrict their total caloric intake by 50% for 48 hours prior to each anthracycline treatment.
Dietary Supplement: 50% caloric restriction
Meals mimicking participant dietary preferences and matching North American macronutrient guidelines will be provided consisting of 50% of total caloric intake for 48 hours

No Intervention: Usual care
The usual care arm will be asked to maintain their typical exercise and diet throughout treatment.



Primary Outcome Measures :
  1. Change in left ventricular ejection fraction reserve (peak exercise - rest) [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Cine steady-state free precession 2- and 4- chamber images will be taken at rest and at peak exercise using a resisted stepping device with a 3 T MRI scanner


Secondary Outcome Measures :
  1. Change in NT-proBNP [ Time Frame: 3-14 days before first anthracycline treatment, 24 hours after 1st and last anthracycline treatments, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    NT-proBNP will be analyzed in serum using electrochemiluminescence sandwich immunoassays

  2. Change in aortic distensibility [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Transverse cine images of the ascending and descending aorta will be taken with a 3 T MRI scanner

  3. Change in skeletal muscle oxygen extraction reserve (peak exercise - rest) [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Susceptometry-based oximetry using deoxyhemoglobin as an intrinsic contrast agent measured at rest and at peak exercise using a resisted plantar flexion device with a 3 T MRI scanner

  4. Change in skeletal muscle oxygen consumption reserve (peak exercise - rest) [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Susceptometry-based oximetry using deoxyhemoglobin as an intrinsic contrast agent, coupled with phase contrast imaging for simultaneous measurement of lower leg blood flow, will together yield oxygen consumption, which will be measured at rest and at peak exercise using a resisted plantar flexion device with a 3 T MRI scanner

  5. Change in resting LV strain [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Strain will be measured from cine steady-state free precession 2- and 4- chamber images will be taken at rest with a 3 T MRI scanner

  6. Change in peak exercise LV strain [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Strain will be measured from cine steady-state free precession 2- and 4- chamber images will be taken at peak exercise using a resisted stepping device with a 3 T MRI scanner

  7. Change in cardiac T1 [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    T1 mapping will performed in a mid-ventricular short-axis slice using saturation recovery single-shot acquisition (SASHA) pulse and Modified Look-Locker inversion recovery (MOLLI) sequencing

  8. Change in peak LVEF [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Cine steady-state free precession 2- and 4- chamber images will be taken at peak exercise using a resisted stepping device with a 3 T MRI scanner

  9. Patient-reported treatment symptoms [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    The Rotterdam Symptom Checklist will be used to rate the prevalence and severity of treatment symptoms

  10. Change in cardiac output [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Cine steady-state free precession will be taken at rest and peak exercise to quantify volumes and will be multiplied by heart rate to determine cardiac output

  11. Change in LV volumes [ Time Frame: Cine steady-state free precession will be taken at rest and peak exercise to quantify volumes and will be multiplied by heart rate to determine cardiac output ]
    Cine steady-state free precession will be taken at rest and peak exercise to quantify volumes

  12. Change in resting LVEF [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Cine steady-state free precession 2- and 4- chamber images will be taken at rest

  13. Change in LV mass [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Mass will be measured using MRI

  14. Change in thigh skeletal muscle mass and quality [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Skeletal muscle mass of the thigh will be measured using Dixon fat-water separation imaging method that yields separated water and fat images to quantify skeletal muscle and adipose tissue.

  15. Change in peak oxygen consumption [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Peak oxygen consumption will measured using a maximal cardiopulmonary exercise test


Other Outcome Measures:
  1. Health-related quality of life and fatigue [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment ]
    Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Fatigue (FACT-F) questionnaire.

  2. Change in clinical tumor size [ Time Frame: Anytime prior to inititiation of chemotherapy, and within 1 month of completion of chemotherapy or as otherwise clinically indicated ]
    Clinical tumor size will be assessed using ultrasound in participants receiving neoadjuvant chemotherapy only

  3. Combined clinical end-point [ Time Frame: 1 and 5 years after completion of treatment ]
    cancer recurrence, cardiac events, hospitalizations, and mortality will be extracted from clinical records and combined into a clinical end-point

  4. Change in circulating markers of oxidative stress/antioxidants [ Time Frame: 3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment ]
    ELISA assays will be used to measure circulating markers of oxidative stress such as MDA and antioxidants such as Mn-SOD. Due to rapid development of these types of assays, samples will be frozen and will be run in batch analysis at the end of the study such that the most modern assays can be used.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • age 18+
  • Female
  • stage I-IIIC breast cancer
  • scheduled to receive an anthracycline-containing chemotherapy protocol
  • able to read and communicate in English
  • willing and able to adhere to either intervention

Exclusion Criteria:

  • contraindications to MRI (e.g. pacemakers, metal implants)
  • contraindications to maximal exercise testing
  • pregnant
  • have orthopedic limitations to sustained exercise on all potential modes (treadmill, elliptical, bike)
  • have a body mass index <19 kg/m2
  • history of eating disorder (self- or oncologist-reported)
  • diabetes
  • severe food allergies or restrictions

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): NCT03131024


Contacts
Contact: Amy A Kirkham, PhD 780-492-8665 amy.kirkham@ualberta.ca
Contact: Richard Thompson, PhD 7804928665 richard.thompson@ualberta.ca

Locations
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2R3
Contact: Amy A Kirkham, PhD    7804926874    amy.kirkham@ualberta.ca   
Contact: Richard Thompson, PhD    780-492-8665    richard.thompson@ualberta.ca   
Sponsors and Collaborators
University of Alberta
Susan G. Komen Breast Cancer Foundation
Investigators
Principal Investigator: Amy A Kirkham, PhD University of Alberta

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT03131024     History of Changes
Other Study ID Numbers: HREBA.CC-17-0129
First Posted: April 27, 2017    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Alberta:
anthracyclines