Capnography-Assisted Learned Monitored (CALM) Breathing Therapy for COPD

Study Overview
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Brief Summary
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This pilot study is part of a phased approach to refine, optimize, and test the feasibility of CALM Breathing. Preliminary participant feedback from the Capnography-Assisted Respiratory Therapy (CART) study was applied to adapt and design CALM Breathing (including its dose, schedule, delivery, and home program). This pilot builds on initial lessons learned and identifies intervention areas still needing greater development to assure the success of a future large trial, targeting a subpopulation at risk, that is, those with COPD and anxiety sensitivity.

Detailed Description
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The purpose of this study is to evaluate an experimental breathing therapy for adults with chronic obstructive pulmonary disease (COPD) called Capnography-Assisted Learned, Monitored (CALM) Breathing. CALM Breathing is an experimental therapy that uses exercises combined with breathing feedback. CALM Breathing promotes self-regulated breathing to relieve symptoms. In sessions, biofeedback of breathing is predominately provided by two devices that are cleared by the Food and Drug Administration (FDA) to measure carbon dioxide at the end of a breath and breathing rate. A capnograph uses tubing at the nose to evaluate levels of carbon dioxide and breathing rate from exhaled air and to display breathing patterns. A pulse oximeter for home use also evaluates breathing rate at the fingertip with a sensor that detects blood flow changes. The investigators are studying CALM Breathing to see if it can relieve shortness of breath and other symptoms; reduce stress; and improve quality of life and exercise tolerance in adults with COPD. The investigators are planning to recruit up to approximately 65 subjects with COPD at Columbia University Irving Medical Center. Participants will be assigned by chance into one of two treatment groups: 1) CALM Breathing or Usual Care (Waitlist). Participants will have an equal chance of being assigned to either group. CALM Breathing is a 4-week therapy program that uses breathing exercises with biofeedback to reduce shortness of breath and other symptoms related to COPD. Biofeedback uses sensors to give information about breathing pattern and airflow to help participants better self-regulate their breathing. Participants assigned by chance to CALM Breathing, will participate in eight breathing therapy sessions, provided twice per week; each session will each take approximately 1-hour. All participants will receive 16-20 standard care pulmonary rehabilitation sessions beginning at approximately week 6-10. Participants will complete three study evaluation visits (at baseline,  6 weeks, and at a 3-month follow-up).

Official Title
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Capnography-Assisted Learned Monitored (CALM) Breathing Therapy for COPD

Conditions
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COPD

Intervention / Treatment
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* Behavioral: CALM Breathing
* Behavioral: Traditional outpatient PR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: be adult males or females have a diagnosis of COPD as defined by FEV1/FVC of < 0.70 on spirometry testing or as shown on a chest computed tomography (CT) receive standard care of pharmacotherapy with bronchodilators (e.g. long-acting beta-agonists, LABAs, or long-acting muscarinic antagonists, or LAMAs) as prescribed by their physician are in stable medical condition as determined by pulmonary rehabilitation physician (i.e., not in need of acute higher level of care such as hospitalization) have dyspnea [as documented in their medical record or based on self-report; e.g., ≥1 on modified Medical Research Council questionnaire (mMRC) dyspnea; or ≥2 dyspnea score on item: Over the last 4 weeks, I have had shortness of breath: almost every day = 4, several days a week = 3, a few days a month = 2, only with lung/respiratory infections = 1, not at all = 0; or yes response of binary presence of dyspnea-related avoidance of activities: Have you avoided any activities due to shortness of breath?)] have elevated dyspnea-related anxiety symptoms: DMQ-CAT dyspnea anxiety score ≤50; or DMQ-CAT activity avoidance ≤50; VAS dyspnea anxiety scale score of ≥20, administered with 6-minute walk test; ASI-16: item #10, It scares me when I become short of breath (at least some); require ≤ 24 hours per day of supplemental oxygen Mini-Mental State Examination score ≥24 speak, read, and write English are stably medicated for at least 4 weeks prior to study entry with long-acting anti-anxiety medication (e.g., selective serotonin reuptake inhibitors, SSRIs, and serotonin norepinephrine reuptake inhibitors, SNRIs), benzodiazepines, or cannabis if prescribed, with no plans to change psychotropic medication dose have not received any pulmonary rehabilitation training in the past 12 months. Exclusion Criteria: are not eligible for pulmonary rehabilitation are actively being treated for cancer have morbid obesity (Body Mass Index (BMI) > 40) have hypercapnia of ETCO2 > 50 mmHg at rest have a musculoskeletal disorder severe enough to interfere with walking or ability to exercise or have neuromuscular disease have had a seizure in the past 3 months reside in an acute hospital, sub-acute care, assisted living, or nursing home are active smokers are pregnant have any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening, which in the opinion of the investigator may put the patient at risk or interfere with study assessments have low literacy as indicated by scores of 4 or 5 (often and always) on the Single Item Literacy Screener (SILS) that asks, How often do you need to have someone help you when you read instructions, pamphlets, or other written material from your doctor or pharmacy? have a diagnosis or medical history of schizophrenia, psychotic disorders, or bipolar disorder as diagnosed by study psychologist have alcohol or substance abuse or dependence within the past 6 months as evaluated by study psychologist have serious suicidal risk (suicidal ideation or suicidal behaviors within the past year) as defined by a score of >1 on psychologist interview-administered Clinician Suicide Assessment Checklist, which is a Modified Columbia-Suicide Severity Rating Scale-CSSRS Take prescribed opioids ≥50 MME (morphine mg equivalents) per day. A dosage threshold of ≥50 MME significantly increases the risk of fatal respiratory depression and necessitates additional precautions. Participants' opioid medication dose will be confirmed by their prescribing physician (e.g., their primary care or pain management doctor). Actively take both prescribed opioids and benzodiazepines. Combining benzodiazepines and opioids significantly increases the risk of respiratory failure in patients with chronic obstructive pulmonary disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: A prospective RCT: In Phase I, participants will be randomized 1:1 to one of two groups: CALM Breathing (N = 25) and Wait-List control (N = 25). In Phase II, both groups will be offered Columbia University's 10-week PR program (care as usual). Access to timely initiation of PR will be facilitated. We will use a hybrid design to evaluate feasibility and acceptability.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CALM Breathing<br> | Behavioral: CALM Breathing<br>* CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.<br>|
| Active Comparator: Wait-List Control<br> | Behavioral: Traditional outpatient PR<br>* After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Participants with High Attendance Rate of CALM Breathing Treatment Sessions | High attendance rate is defined as greater than or equal to 70% (where 100% = all 8 sessions attended). | 3 months | 
| Acceptability Aim #2 CALM Breathing Attendance | The acceptability of the CALM Breathing therapy will be evaluated based on mixed methods data collected from CALM Breathing attendance, drop-out, and satisfaction ratings, and from semi-structured interviews. Acceptability will be determined in part by whether or not we achieve a ≥70% CALM Breathing attendance. | 3 months | 
| Acceptability Aim #2 Drop-Out Rate | The acceptability of the CALM Breathing therapy will be evaluated based on mixed methods data collected from CALM Breathing attendance, drop-out, and satisfaction ratings, and from semi-structured interviews. Acceptability will be determined in part by whether or not we achieve a CALM Breathing drop-out rate of ≤10-15%. | 3 months | 
| Acceptability Aim #2 CALM Breathing Satisfaction | The acceptability of the CALM Breathing therapy will be evaluated based on mixed methods data collected from CALM Breathing attendance, drop-out, and satisfaction ratings, and semi-structured interviews. Acceptability will be determined in part by whether or not we achieve a mean of ≥2 good satisfaction rating for CALM Breathing treatment overall (item 8 of FACIT; (0-4 scale). Higher scores indicate more satisfaction. Single FACIT Treatment Satisfaction items (6 and 8) ask: (1) Would you recommend this treatment to others with your illness? (with 0-2 rating scale, 0 = No, 1 = Maybe, 2 = Yes); and (2) How do you rate this treatment [CALM Breathing] overall? (with 0-4 rating scale, 0 = poor and 4 = excellent). The investigators will also ask, How do you rate the CALM Breathing home exercises overall? (and use the same FACIT 0-4 rating scale). | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Respiratory Disease Questionnaire (CRQ) Score | This questionnaire measures the impact of chronic obstructive pulmonary disease (COPD) on a person's life. It consists of 20 items across 4 domains (dyspnea, fatigue, emotional function, and master). Items are on a 7-point Likert scale (1 - 7) and are scored from 1 (most severe) to 7 (no impairment) (better outcome). For this trial, questions 4a- 4e are included which is the dyspnea domain. The 5 scores are summated and divided by the number of items. The range is 1-7. Higher scores indicate better outcomes. | 3 months | 
| Dyspnea management Questionnaire Computer Adaptive test (DMQ-CAT) Score | The DMQ-CAT is a 71-item questionnaire that measures dyspnea anxiety. Raw scores range from 0 (low) to 6 (high). These raw scores are transformed into item response theory (IRT) calibrations with a mean score of 50 and a standard deviation of ±10. The full range is 0 to 100. The DQM-CAT software automatically scores these scales. Higher scores indicate better outcomes. | 3 months | 
| Modified Borg Scale Score | The Modified Borg Scale is most commonly used to assess symptoms of breathlessness. On the 11-item scale, a score of 0 indicates No Exertion and a score of 10 indicates Maximal exertion (10-point scale). The full range is 0-10. Higher scores indicate worse outcomes (i.e. more exertion). An average of the pre-Tx, post-Tx, and 3-month 6-Minute Walk Test Modified Borg Scale Scores could be reported (taken from all participants). | 3 months | 
| Generalized Anxiety Disorder-7 (GAD-7) Score | The General Anxiety Disorder-7 is a 7-item screening tool and symptom severity measure for the four most common anxiety disorders. This is calculated by assigning scores of 0 (not at all), 1 (several days'), 2 (more than half the days), or 3 (nearly every day). GAD-7 total score for the seven items ranges from 0 to 21. Higher scores indicate worse outcomes (i.e. greater anxiety). | 3 months | 
| Perceived Stress Scale Score (PSS) | The PSS is a 10-item classic stress assessment instrument. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. | 3 months | 
| 6 mile Walking Distance Score (6MinWT) | This is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. | 3 months | 
| Physical Activity Scale for the Elderly (PASE) | This 12-item questionnaire uses frequency, duration, and intensity level of activity over the previous week to assign a score, ranging from 0 to 793, with higher scores indicating greater physical activity. | 3 months | 
| COPD Assessment Test (CAT) | The CAT quantifies the impact of COPD symptoms on patients' overall health. Participants assign a score ranging from 0 to 5 for each of the 8 areas. A score of 0 means there is no impairment in that area. A score of 5 means severe impairment. Your overall score will range from 0 to 40. The score is a composite score. | 3 months | 
| Patient-Reported Outcomes Measurement Information System (PROMIS-24). | This is a 10-item tool used to measure patient-reported outcomes (PROs) relevant across common medical conditions. The response options are presented as a 5-point rating scale, with higher scores indicating a healthier patient (better outcome). Scores are standardized to the general population using the T-Score, with the average T-score for the US population is 50 points, with a SD of 10 points. | 3 months | 
| End-tidal CO2 | This measures the partial pressure of CO2 at the end of an exhaled breath. | 3 months | 
| Respiratory Rate (RR) | The RR will be measured as total number of breaths per minute. | 3 months | 
| Predicted Forced Expiratory Volume (FEV1) Percentage | Percent of predicted forced expiratory volume (FEV) in 1 second. | 3 months | 
| Forced vital capacity (FVC) | FVC measures the total amount of air exhaled during the FEV test. | 3 months | 
| Ratio of FEV1/FVC | Ratio of FEV1/FVC based on American Thoracic Society (ATS) guidelines and will be calculated from the FEV1 and FVC values. This is used to confirm diagnosis of COPD. | 3 months | 
| Pulmonary Rehabilitation Engagement | Uptake; treatment initiation; attrition; and patient activation using the Patient Activation Measure. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breathing, Anxiety