High-intensity Exercise After Treatment (HEAT)

Enhancing Cognitive and Cardiovascular Function in Breast Cancer Survivors Through High-intensity Interval Training

This pilot study tests the feasibility and preliminary efficacy of an 8-week, 3-arm pilot exercise trial in which 45 breast cancer survivors will be randomized to high-intensity interval training (HIIT; n=15), moderate-intensity aerobic training (MOD; n=15), or Usual Care (UC; n=15).

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Breast Neoplasm Female
• Intervention / Treatment: Behavioral: High-Intensity Interval Training; Behavioral: Moderate-Intensity Exercise

Detailed Description

Aim 1: Determine the feasibility and acceptability of an 8-week high-intensity interval training (HIIT) program compared with a standard moderate-intensity aerobic training (MOD) program in 45 breast cancer survivors prescribed aromatase inhibitors.

Aim 2: Calculate effect sizes associated with the 8-week HIIT program, compared with MOD and Usual Care (UC), on cognitive and cardiovascular functions in 45 breast cancer survivors.

Eligible individuals will be women diagnosed with Stages I-IIIa breast cancer, have completed primary treatment (i.e., surgery, chemotherapy, and/or radiation therapy), and currently prescribed an aromatase inhibitor. The specific aims are: 1) Determine the feasibility and acceptability of an 8-week high-intensity interval training (HIIT) program compared with a standard moderate-intensity (MOD) program; and 2) Calculate effect sizes associated with the 8-week HIIT program, compared with MOD and usual care (UC), on cognitive and cardiovascular functions. Cognitive function is operationalized as performance on executive function and working memory tasks. Cardiovascular function is operationalized as exercise capacity (VO2peak, heart rate recovery), resting function (heart rate, blood pressure), and cardiovascular structure/function (arterial stiffness, arterial wall thickness, endothelial function). Associations between change in cardiovascular outcomes and change in cognitive outcomes across the intervention period will also be explored.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult female (aged 19 or older)
• First, primary diagnosis of Stage I-IIIa breast cancer
• Hormone receptor positive (ER+ and/or PR+) diagnosis
• Human epidermal growth factor receptor 2 negative (HER2-) diagnosis
• Completed primary adjuvant treatment (i.e., surgery, chemotherapy, and/or radiation therapy)
• Currently prescribed an aromatase inhibitor
• No evidence of possible cognitive impairment as assessed using the Telephone Interview of Cognitive Status (TICS-M; score >21)
• Sedentary except for casual lifestyle recreation. This is defined as self-reporting 20+ minutes of exercise physical activity on 2 or fewer days per week within the previous six months.
• Receive physician's clearance to participate in an exercise program
• Agree to be randomized
• Fully vaccinated for COVID-19 ≥2 weeks prior to participation
• Provide written informed consent to participate in study

Exclusion Criteria:

• Males.
• Stage 0 breast cancer diagnosis or metastatic disease
• Currently receiving chemotherapy or radiation therapy for any cancer
• Scheduled to receive breast surgery (e.g., mastectomy, reconstructive surgery) during the study period
• Second cancer diagnosis (excluding non-invasive skin cancers; including breast cancer recurrence)
• Self-report an 20+ minutes of exercise physical activity on 3+ days per week for the previous 6 months
• Pregnant or plan to become pregnant during study period.
• Is not cleared to participate in exercise by a physician.
• Enrolled in another physical activity program
• Unable to cycle on a stationary bike
• Unwilling to complete study requirements
• History of stroke, transient ischemic attack, other neurological disorders, or brain surgery involving tissue removal
• Clinically significant TICS-M score (<21) during baseline procedures
• Not fully vaccinated for COVID-19

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Intensity Interval Training (HIIT); Breast cancer survivors randomized to HIIT will participate in a high-intensity interval training program for 8 weeks.	Behavioral: High-Intensity Interval Training; HIIT is a type of training in which short periods of high-intensity anaerobic exercise (1-4 minutes at 80-95% of VO2peak) are alternated with less intense aerobic recovery periods (1-3 minutes at 50-60% VO2peak). Individually-tailored exercise prescriptions will be developed based upon each participant's baseline maximal graded exercise test (heart rate corresponding with %VO2 peak) and symptom limitation. Sessions will be progressive in nature such that the volume of exercise (i.e., number and intensity of intervals) increases across weeks. Intervals will progress from a heart rate corresponding with 75% VO2peak in Week 1 to 90-95% VO2peak in Weeks 5-8. Sessions will be ~30 minutes in length. Indoor cycling is the primary mode of exercise.
Active Comparator: Moderate-Intensity Exercise (MOD); Breast cancer survivors randomized to MOD will participate in a moderate-intensity aerobic exercise program for 8 weeks.	Behavioral: Moderate-Intensity Exercise; Individually-tailored exercise prescriptions will be developed based upon each participant's baseline maximal graded exercise test (heart rate corresponding with %VO2 peak) and symptom limitation. Sessions will be progressive in nature such that the volume of exercise increases across weeks. Indoor cycling is the primary mode of exercise. Sessions will include moderate-intensity cycling that progresses from a heart rate corresponding with 55-60% VO2peak for 30 minutes in Week 1 to 65-70% VO2peak for 45-50 minutes in Weeks 5-8.
No Intervention: Usual Care (UC); Individuals randomized to UC will be instructed to continue standard cancer care and engage in habitual lifestyle behaviors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participation Rate	Sample size / [1-(#ineligible/# exposed to recruitment)*(#exposed to recruitment)]	Baseline
Adherence to the exercise programs	average number of exercise sessions (out of 24) attended	post-intervention (Week 9)
Compliance of the exercise programs	average number of exercise sessions (out of 24) in which the prescribed exercise duration and intensity are achieved	post-intervention
Acceptability of the exercise programs	satisfaction with the exercise program as measured by a satisfaction survey. Survey uses a 5-point Likert-type scale. Satisfaction for each item is defined as reporting 4-5 on the scale (i.e., somewhat agree or completely agree).	post-intervention
Change in executive function processing	Change in completion time on Trails B task, with higher values indicating lower executive function.	Baseline, post-intervention (Week 9)
Change in cognitive flexibility	Change in reaction time on Task-switch task, with higher values indicating lower cognitive flexibility	Baseline, post-intervention (Week 9)
Change in spatial working memory reaction time	Change in reaction time on spatial working memory task, with faster reaction times indicating better spatial working memory	Baseline, post-intervention (Week 9)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiorespiratory Fitness	Change in Peak VO2 as measured by a modified Balke treadmill graded exercise test protocol.	Baseline, post-intervention (Week 9)
Carotid arterial wall thickness	will be estimated from vascular ultrasound and expressed as average and maximum mm	Baseline, post-intervention (Week 9)
Endothelial function	estimated from brachial artery flow mediated dilation and expressed as percent change in brachial artery diameter relative to baseline diameter	Baseline, post-intervention (Week 9)

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Diane Ehlers, PhD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: physical activity; breast cancer; exercise; cognitive function; cardiovascular function
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 0439-21-FB; 1U54GM115458 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Although the final dataset will not include identifying information, there is still a possibility of deductive disclosure of identity. Therefore, data will not be shared via an NIH or approved public repository; however, we will share de-identified data as required for publication in scientific journals and with outside collaborators and scientists upon request.
• IPD Sharing Time Frame: Data will be shared via scientific journals at the time of publication and with outside collaborators before publication.
• IPD Sharing Access Criteria: We will make data available to researchers who agree to use the data only for research purposes, protect the data using secure computer technologies, and destroy the data after relevant analyses are completed and manuscripts published.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No