Get REAL and HEEL Research Program

The UNC Get REAL & HEEL (GR&H) program has provided after treatment support for women with a breast cancer diagnosis since 2006. The 16-week program includes an individualized training program and the opportunity to continue working out in the GR&H facilities at the conclusion of the 16-week program. The purpose of this protocol is to implement a research agenda at GR&H that will examine the efficacy of the program. The primary aim of this study is a pre-post test of the impact of the GR&H program (standardized combination of aerobic and resistance training) on VO2peak1,2. The secondary aims of this study are to evaluate quality of life as well as cardiorespiratory function (vascular health), physical function (muscular strength, body composition), cognition, balance, and patient-reported outcomes (fatigue, depression, anxiety, quality of life). Exploratory aims are focused on evaluating the impact of exercise on biomarkers: (1) aging - p16INK4a, (2) immune cell function - total leukocyte count, T and natural killer cells, monocytes, and neutrophils count and activity, and (3) circulating pro- and anti-inflammatory cytokines.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Behavioral: 16-week Exercise Rehabilitation Program for Breast Cancer Survivors

Detailed Description

Objectives:

Primary:

Evaluate the impact of the Get REAL and HEEL research program (standardized combination of aerobic and resistance training) on change in V02peak from pre to post 16-week intervention.

Secondary:

Evaluate the impact of the GR&H program (standardized combination of aerobic and resistance training) on change in cardiorespiratory function, immunology, physical function parameters, cognition, balance, and patient-reported outcomes from pre to post 16-week intervention.

Evaluate changes in all measures annually over the 5 year follow-up period.

Report on enrollment, recruitment, and attrition.

Exploratory Objectives

The investigator's exploratory aims are focused on evaluating the impact of exercise on biomarkers: (1) aging - p16INK4a, (2) total leukocyte, lymphocyte (T cells and natural killer cells), monocyte and neutrophil counts and T cell proliferation assays, natural killer cytotoxicity assays, and cytokine production from stimulated neutrophils and monocytes, and (3) circulating pro- and anti-inflammatory cytokines.

OUTLINE:

Participants will complete pre-intervention assessments, questionnaires and blood draw at week 1 and 2 pre-intervention, followed by a 16-week aerobic and resistance training exercise program (intervention). Participants will complete assessments, questionnaires and blood draws at week 1 and 2 following the intervention and then again at 6 months and 12 months following intervention. Questionnaires only will be administered at year 2, 3,4 and 5 following intervention.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • North Carolina Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Potential study participants with confirmed early-stage breast cancer will be screened through a review of daily clinic schedules for patients seen at the North Carolina Cancer Hospital. Patients must have recently completed their initial treatment (be within one year of completion).

Description

Inclusion Criteria:

Patients will be eligible for this protocol if they have

• histologically confirmed early stage (non-metastatic) breast cancer
• and have recently (within 1 year) completed their initial treatment (they may continue to be on endocrine treatment).

No exclusions will be made based on ethnicity or race, although patients must be able to read and speak English.

Participants must provide IRB-approved signed written informed consent. The consent includes access to their medical records, including demographic and billing information, diagnoses, treatments, and laboratory results. Participants may also be asked to provide permission to contact their non-UNC doctors for additional medical record information, and may also require a medical release from various treating physicians.

Interested persons must agree to adhere to the 16-week GR&H protocol and complete all blood draws, assessments and questionnaires to the best of their ability. The informed consent will also include annual follow-up assessments and questionnaires for up to 5 years after they have completed the 16-week program.

Patients who are approached about participating in LCCC1630 and decline to do so are able to join GR&H as a supportive care program.

Exclusion Criteria:

Interested persons will be excluded from study participation if

• they do not have evidence of a cancer diagnosis or completion of surgery, radiation and/or chemotherapy treatment,
• or if they have previously completed the GR&H exercise program. Entirely at the discretion of GR&H investigators, physical function and other assessments conducted at baseline may also determine that a patient is not medically suitable for the GR&H protocol. Consented patients who are determined to be medically not suited for the GR&H protocol (unevaluable) will remain in the study for analyses comparing those who are evaluable with those who are not.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

16-week Exercise Program; Interested patients will attend a group meeting where they will be screened and consented to the study. During weeks 1 and 2 patients will complete pre-intervention baseline assessments and blood draws followed by a 16-week supervised exercise program at Get REEL and HEAL facility. Study participants will complete progressive aerobic and resistance exercise training. Post-intervention weeks 1 and 2 participants will complete assessments, questionnaires and blood draws. Participants will be followed up at 6 and 12 months post intervention with physical assessments, questionnaires and blood draws. Annual follow-up will occur at year 2,3,4 and 5 post intervention with questionnaires only.

Behavioral: 16-week Exercise Rehabilitation Program for Breast Cancer Survivors; Interested patients will attend a group meeting where they will be screened and consented to the study. During weeks 1 and 2 patients will complete pre-intervention baseline assessments and blood draws followed by a 16-week supervised exercise program at Get REEL and HEAL facility. Study participants will complete progressive aerobic and resistance exercise training. Post-intervention weeks 1 and 2 participants will complete assessments, questionnaires and blood draws. Participants will be followed up at 6 and 12 months post intervention with physical assessments, questionnaires and blood draws. Annual follow-up will occur at year 2,3,4 and 5 post intervention with questionnaires only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiopulmonary exercise test with NIRS and PWA (vascular function)	The Cardiopulmonary Exercise Test (CPET) with NIRS and PWA will be used to measure peak oxygen content (VO2peak), tissue oxygen saturation and pulse wave analysis during this symptom-limited exercise test.	Pre-intervention (weeks 1-2), Post-intervention (weeks 17 or 18), 6 months post-intervention, 12-months post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometrics-Height	Measure Height	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6 months post intervention, 12 months post-intervention
Anthropometrics-Weight	Weight	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6 months post intervention, 12 months post-intervention
Anthropometrics-BMI	Measure BMI	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6 months post intervention, 12 months post-intervention
Anthropometrics-Blood Pressure	Measure blood pressure -- both systolic and diastolic	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6 months post intervention, 12 months post-intervention
Anthropometrics-Resting Heart Rate	Measure Resting Heart Rate	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6 months post intervention, 12 months post-intervention
Body Composition	DEXA -- Body Composition will be perfomed using a Hologic (Discovery W) Dual X-ray Absorptiometry (DEXA) located in the EORL. Total body weight-mass (BW) and compositional aspects of lean body mass (LBM), fat tissue mass (FM), and percentage body fat (% BF) will be examined using standard DEXA screening procedures. The BW will be measured using a high grade analytical balance-scale (accuracy ± 10 grams).	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6 months post-intervention, 12 months post-intervention
Measure of muscle composition -- proportion of body fat to lean muscle mass	Ultrasound -- LogicView™ software (General Electric Company, Milwaukee, WI, USA) will be used to generate real-time panoramic cross-sectional images of the VL. Three panoramic scans at a gain of 50dB and a depth of 5.0 cm. All image analyses will be completed using Image-J software (version 1.46r, National Institutes of Health, USA) with each image area individually scaled from pixels to centimeters via the straight-line function. The polygon function will be used to determine the CSA of the VL by selecting a region including mostly muscle and minimal surrounding fascia. Greater EI values represent greater fibrous (non-muscular) composition.	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Vascular Function	XCEL Sphygmacor+USCOM	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Resting ECG	Resting electrocardiogram -- Individual wave/complex/intervals components and overall ECG tracings will be assessed using a 12-lead ECG. The study Cardiologist will review each report individually at baseline prior to the Cardiopulmonary Exercise Test for evidence of overt cardiac dysfunction and will deem the potential study participant appropriate/not appropriate for exercise testing.	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Functional Tests	6-minute walk	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Functional Tests	Timed Up and Go	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Cognitive Testing	Administer DKEFS	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Cognitive Testing	Administer Digit Span	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Cognitive Testing	Administer Sequencing	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Cognitive Testing	Administer HVLT-R	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Cognitive Testing	Administer TMT	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Cognitive Testing	Administer NeuroCom balance test	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Muscle Strength and Power	Isokinetic, isometric handgrip tests	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Blood Draw	30 mL Blood draw for non-subset group	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Satisfaction with GR&H Questionnaire	Administer Satisfaction with GR&H Questionnaire	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention
Acute exercise bout with blood draw for immune/inflammatory parameters (subset group only)	Cannulated, 3 blood draws over course of 45 minute visit. 50 mL total collected pre-intervention and post intervention; 30 mL total collected at 6 months and 12 months post-intervention	Pre-intervention (weeks 1-2), post-intervention (weeks 17 or 18), 6-months post-intervention, 12-months post-intervention

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Claudio L Battaglini, PhD, UNC Lineberger Comprehensive Cancer Center; Study Director: Kirsten Nyrop, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

General Publications

• Wagoner CW, Lee JT, Hanson ED, Kerr ZY, Nyrop KA, Muss HB, Battaglini CL. Baseline fatigue in early breast cancer survivors: understanding its prevalence in community-based exercise. Support Care Cancer. 2022 May;30(5):4407-4416. doi: 10.1007/s00520-021-06776-8. Epub 2022 Jan 31.
• Bartlett DB, Hanson ED, Lee JT, Wagoner CW, Harrell EP, Sullivan SA, Bates LC, Alzer MS, Amatuli DJ, Deal AM, Jensen BC, MacDonald G, Deal MA, Muss HB, Nyrop KA, Battaglini CL. The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors. Front Immunol. 2021 Oct 27;12:733101. doi: 10.3389/fimmu.2021.733101. eCollection 2021.
• Hanson ED, Bates LC, Harrell EP, Bartlett DB, Lee JT, Wagoner CW, Alzer MS, Amatuli DJ, Jensen BC, Deal AM, Muss HB, Nyrop KA, Battaglini CL. Exercise training partially rescues impaired mucosal associated invariant t-cell mobilization in breast cancer survivors compared to healthy older women. Exp Gerontol. 2021 Sep;152:111454. doi: 10.1016/j.exger.2021.111454. Epub 2021 Jun 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2017
• Primary Completion (Actual): March 9, 2019
• Study Completion (Actual): February 12, 2020

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: LCCC 1630

Drug and device information, study documents

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