Simulated-altitude to Optimize Aerobic Exercise Among Breast Cancer Survivors With Limited Mobility

Study Overview
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Brief Summary
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The study will evaluate the utility of hypoxic exercise training to improve cardiovascular and metabolic health among obese breast cancer survivors. While participants exercise, a lower fraction of inspired oxygen will be used to simulate a higher altitude. This approach removes the mechanical strain needed to sustain moderate-to-vigorous exercise intensity which is believed to support exercise tolerance. Participants are randomized to either the treatment (walking+simulated-altitude) or control (walking under normoxic conditions).

Detailed Description
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Cancer survivors have a two-fold greater risk of having one or more functional limitations compared to those without a history of cancer. Though exercise interventions in breast cancer survivors exist, a large portion of women (61%) exhibit some form of lower-body dysfunction that severely restricts participation in physical activity and exercise. Both physical and emotional well-being are negatively affected by the combination of increased adiposity, orthopedic problems and muscle weakness, thus reinforcing a cycle of physical inactivity. For these reasons, obese breast cancer survivors with walking limitations are faced with a barrier that greatly increases the difficulty of meeting prescribed exercise guidelines (≥150 weekly minutes of moderate-to-vigorous intensity exercise). Though previous investigations have demonstrated the safety and benefits of exercise+simulated altitude to improve body fat, physical endurance and insulin sensitivity, results have been limited to non-cancer participants only. Given the comorbidities common to breast cancer survivors, specifically, heart disease risk, lower body joint problems, low aerobic capacity, and fatigue, further research is needed.

Official Title
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Simulated-Altitude as an Adjunct to Optimize Aerobic Exercise in Obese Breast Cancer Survivors With Limited Ambulatory Function: Pilot Randomized Trial

Conditions
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Obesity, Breast Cancer

Intervention / Treatment
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* Other: Walking+simulated-altitude
* Behavioral: Walking (control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician's medical clearance for participation English-speaking women 18-70 years of age with a history of Stage 0-III breast cancer Preferred walking speed of less than 2.9 mph as measured by a timed 10 meter walk test (to be performed on-site after consent during preliminary screening) OR the inability to complete a 6-minute walk without stopping (to be performed on-site after consent during preliminary screening) Body mass index between 30-45 kg/m2 ≥1 year post-treatment and not currently receiving or planning to receive chemo/radiation therapies Not participating in a structured exercise routine In the previous 6 months, not engaging in (on average) ≥60 minutes of moderate or ≥30 minutes of vigorous physical activity per week. Exclusion Criteria: Males Dementia Medical, psychological, and/or social characteristics that may interfere with the ability to fully participate in the proposed study activities/assessments (e.g., psychosis, schizophrenia) Contraindication to participate in regular exercise training Unwilling to complete prescribed exercise Inability to walk Pregnant Resting oxygen saturation via pulse oximetry below 90% Using home oxygen therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Walking+simulated-altitude<br>8-week exercise training program that involves 3 supervised, treadmill walking sessions each week with 16% oxygen, which will be administered through an exercise mask. | Other: Walking+simulated-altitude<br>* Participants will walk on a treadmill for up to 50 minutes at a 16% oxygen level (administered via exercise mask), which is similar in altitude to Flagstaff, AZ. The progression of exercise training will be based on a varying percents of heart rate reserve.<br>|
| Active Comparator: Walking (control)<br>8-week exercise training program that involves 3 supervised, treadmill walking session each week. | Behavioral: Walking (control)<br>* Participants will walk on a treadmill for up to 50 minutes.The progression of exercise training will be based on a varying percents of heart rate reserve.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the feasibility of an 8 week exercise intervention comparing walking+simulated-altitude to walking (control) based on retention. | number of participants completing the 8 week session | baseline to 8 weeks | 
| Determine the feasibility of an 8 week exercise intervention comparing walking+simulated-altitude to walking (control) based on adherence to exercise compliance. | mean compliance among all participantswith exercise prescription | baseline to 8 weeks | 
| Determine the feasibility of an 8 week exercise intervention comparing walking+simulated-altitude to walking (control) based on number of adverse events. | Number of adverse events in each group | baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect sizes for walking+simulated-altitude and walking (control) as measured by a 6 minute walk. | 6 minute walk test, a valid and reliable tool in cancer survivors will be used to evaluate cardiovascular health and mobility. Total distance (in meters) covered over the duration of 6 minutes will be recorded. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by the cardiorespiratory fitness. | Cardiorespiratory fitness, will be measured by indirect calorimetry during a graded walking test on a treadmill to estimate peak aerobic capacity. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by arterial elasticity. | Arterial elasticity, will be measured by local pulse contour analyses (HDI/Pulse Wave), A non-invasive procedure based on a modified Windkessel model which permits the evaluation of vascular health. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by resting heart rate variability. | Heart rate variability, will be determined by R-to-R interval variations in heart rate, used to index sympatho-vagal balance. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by the fasting glucose. | Typically, a normal blood sugar level is identified by experts as anything less than 100 mg/dL after a period of fasting. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by C-reactive protein (mg/L) serum assays. | Serum assays, will be measured following an overnight to evaluate metabolic and cardiovascular health. Standards practices will be implemented. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by tumor-necrosis factor-alpha (pg/mL) assays. | Serum assays, will be measured following an overnight to evaluate metabolic and cardiovascular health. Standards practices will be implemented. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by interleukin-6 (pg/mL) serum assays. | Serum assays, will be measured following an overnight to evaluate metabolic and cardiovascular health. Standards practices will be implemented. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by interleukin-10 (pg/mL) serum assays. | Serum assays, will be measured following an overnight to evaluate metabolic and cardiovascular health. Standards practices will be implemented. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by body composition (% body fat). | Body composition, will be measured by dual-energy X-ray absorptiometry during which participants will be scanned while lying supine in light clothing with their arms at their sides. | baseline to 8 weeks | 
| The effect sizes for walking+simulated-altitude and walking (control) as measured by free-living physical activity. | Free-living physical activity, will be measured by a triaxial accelerometer (e.g., Actigraph GT3X). Participants will wear the accelerometer on the hip of their non-dominant side during waking periods and around the wrist when sleeping according to a previously published protocol. | baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Cancer, Obesity