Get REAL and HEEL Research Program

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Get REAL and HEEL Research Program

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Behavioral: 16-week Exercise Rehabilitation Program for Breast Cancer Survivors


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 16-week Exercise Program<br>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<br>* 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.<br>|

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 |