Caloric Restriction and Exercise for Protection From Anthracycline Toxic Effects

NCT03131024 | Completed

• 1 other identifier: HREBA.CC-17-0129
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer Female

Keywords

anthracyclines

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular ejection fraction reserve (peak exercise - rest)

  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

  3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment

Secondary Outcomes (15)

• Change in NT-proBNP

  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

• Change in aortic distensibility

  3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment

• Change in skeletal muscle oxygen extraction reserve (peak exercise - rest)

  3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment

• Change in skeletal muscle oxygen consumption reserve (peak exercise - rest)

  3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment

• Change in resting LV strain

  3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment

Other Outcomes (4)

• Health-related quality of life and fatigue

  3-14 days before first anthracycline treatment, 2-3 weeks after completion of anthracycline treatment, one year after initiation of anthracycline treatment

• Change in clinical tumor size

  Anytime prior to inititiation of chemotherapy, and within 1 month of completion of chemotherapy or as otherwise clinically indicated

• Combined clinical end-point

  1 and 5 years after completion of treatment

Study Arms (3)

Aerobic exercise

EXPERIMENTAL

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

50% caloric restriction

EXPERIMENTAL

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

Usual care

NO INTERVENTION

The usual care arm will be asked to maintain their typical exercise and diet throughout treatment.

Interventions

50% caloric restriction DIETARY_SUPPLEMENT

Meals mimicking participant dietary preferences and matching North American macronutrient guidelines will be provided consisting of 50% of total caloric intake for 48 hours

50% caloric restriction

Aerobic exercise OTHER

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

Aerobic exercise

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead
• Susan G. Komen Breast Cancer Foundation: collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

Related Publications (1)

• Kirkham AA, Paterson DI, Prado CM, Mackey JR, Courneya KS, Pituskin E, Thompson RB. Rationale and design of the Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study: a 3-arm parallel group phase II randomized controlled trial in early breast cancer. BMC Cancer. 2018 Sep 3;18(1):864. doi: 10.1186/s12885-018-4778-7.

  PMID: 30176834 DERIVED

MeSH Terms

Interventions

Caloric Restriction; Exercise

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Amy A Kirkham, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: April 27, 2017
• Study Start: October 15, 2017
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: September 19, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)