High-Flow Oxygen in Reducing Shortness of Breath Caused by Exercise in Patients With Cancer

Study Overview
=================
Brief Summary
-----------------
This randomized phase II trial studies how well high-flow oxygen works in reducing difficulty breathing during exercise (exertional dyspnea) in patients with cancer. Dyspnea is linked to decreased lung function, quality of life, and survival. High-flow oxygen is a device that delivers heated and humidified oxygen through the nose. This may be effective in reducing dyspnea, and may help patients' lungs function better and improve their quality of life.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Obtain preliminary estimates of the effect size of oxygen and high flow rate on exertional dyspnea (modified Borg Scale adjusted for work rate and baseline dyspnea). SECONDARY OBJECTIVES: I. Determine the completion rate of a randomized controlled trial of exertional dyspnea in cancer patients. II. Obtain preliminary estimates of the effects of oxygen and flow rate on physiologic function (respiratory rate and oxygen saturation) and exercise capacity (work rate and exercise duration). OUTLINE: All patients undergo a baseline structured exercise session with air. Patients are then randomized to 1 of 4 treatments for a second session approximately 3 days later. ARM I: Patients receive high-flow oxygen via nasal prongs during a structured stationary bicycle exercise session. ARM II: Patients receive high-flow air via nasal prongs during a structured stationary bicycle exercise session. ARM III: Patients receive low-flow oxygen via a nasal cannula during a structured stationary bicycle exercise session. ARM IV: Patients receive low-flow air via a nasal cannula during structured stationary bicycle exercise session.

Official Title
-----------------
High-Flow Oxygen for Exertional Dyspnea in Cancer Patients

Conditions
-----------------
Dyspnea, Malignant Neoplasm

Intervention / Treatment
-----------------
* Procedure: Oxygen Therapy
* Procedure: Oxygen Therapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Procedure: Respiratory Therapy
* Procedure: Respiratory Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of cancer, with evidence of primary or secondary lung involvement Average dyspnea Borg Scale >= 4 of 10 with severe exertion over the past week Oxygen saturation > 90% on ambient air at time of assessment Able to communicate in English or Spanish Karnofsky performance status >= 50% Seen at Supportive Care, cardiopulmonary center, thoracic radiation oncology or thoracic medical oncology Exclusion Criteria: Resting dyspnea modified Borg Scale > 7 of 10 at enrollment Severe obstructive lung disease (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] < 70% post bronchodilator and forced expiratory volume in 1 second < 30% predicted) Delirium (i.e., Memorial Delirium Rating Scale > 13) History of unstable angina or myocardial infarction in the last week Acute pulmonary embolus or pulmonary infarction in the last week Thrombosis of lower extremities in the last week Acute myocarditis, pericarditis, or endocarditis in the last week Symptomatic aortic stenosis or syncope in the last week Suspected dissecting aneurysm Severe untreated resting arterial hypertension (> 200 mmHg systolic, > 120 mmHg diastolic) at the time of enrollment Uncontrolled arrhythmias causing symptoms or hemodynamic compromise in the last week Uncontrolled heart failure in the last week Pleural effusion requiring thoracentesis within 1 week of study enrollment or scheduled during the study period Airway obstruction requiring stenting within 1 week of study enrollment or scheduled during the study period Pneumonia requiring antibiotics at the time of study enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (high-flow oxygen)<br>Patients receive high-flow oxygen via nasal prongs during a structured stationary bicycle exercise session. | Procedure: Oxygen Therapy<br>* Receive high-flow oxygen<br>* Other names: supplemental oxygen therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (high-flow air)<br>Patients receive high-flow air via nasal prongs during a structured stationary bicycle exercise session | Procedure: Oxygen Therapy<br>* Receive high-flow air<br>* Other names: supplemental oxygen therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm III (low-flow oxygen)<br>Patients receive low-flow oxygen via a nasal cannula during a structured stationary bicycle exercise session. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Respiratory Therapy<br>* Receive low-flow oxygen<br>|
| Active Comparator: Arm IV (low-flow air)<br>Patients receive low-flow air via a nasal cannula during a structured stationary bicycle exercise session. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Respiratory Therapy<br>* Receive low-flow air<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Borg Scale Dyspnea Intensity at Isotime | Assessed Dyspnea using the Modified Borg Scale Dyspnea Intensity that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath) at Isotime. Measured the mean difference of Modified Borg Scale Dyspnea Intensity at isotime between the second exercise test (in which all patients received Low Flow Oxygen) and the third exercise tests (in which all patients received the assigned intervention). | End of second exercise test and end of third exercise test, approximately up to 12 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test) | Dyspnea unpleasantness was measured using the Modified Borg Scale Dyspnea Intensity that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Dyspnea intensity was measured every minute. The number of minutes varied by patient, per test. It was measured as pairwise difference of slope (taking 'low flow air' arm as a reference). This linear mixed model was constructed based on the following: Dyspnea Unpleasantness at third test = Minutes + Study Arm + Study Arm*Minutes + Total work rate + Slope of Dyspnea Unpleasantness and Minutes at Second test + Minutes at second test. | Third exercise test, approximately up to 12 minutes | 
| Modified Borg Scale Leg Discomfort | Leg discomfort was measured using the Modified Borg Scale Leg discomfort that ranges from 0 (no discomfort) to 10 (worst possible discomfort) during the constant work exercise of third test. Leg discomfort was measured every minute. The number of minutes varied by patient, per test. It was measured as pairwise difference of slope (taking 'low flow air' arm as a reference). This linear mixed model was constructed based on the following: Leg Discomfort at third test = Minutes + Study Arm + Study Arm*Minutes + Total work rate + Slope of Leg Discomfort and Minutes at Second test + Minutes at Second test. | Third exercise test, approximately up to 12 minutes | 
| Exercise Endurance | The Exercise endurance was measured as a mean duration of constant work in minutes during third test. It was measured as pairwise comparison of mean difference of exercise duration (taking 'low flow air' as a reference). This linear mixed model was constructed based on the following: Time at third test = Study Arm + Minutes at Second test. Detail output from the mixed models | End of third exercise test, approximately up to 12 minutes | 
| Adverse Events | Adverse effects related to supplemental oxygen use were assessed using a numeric rating scale from 0 (not at all) to 10 (worst possible) before and after the study intervention. The mean change was measured before and after the 3rd test ranging between -10 (improvement) and +10 (deterioration). | Before and after 3rd test during intervention phase, approximately up to 12 minutes |