Breathe Easier II: A Dyad-based Multiple Behavior Intervention

Study Overview
=================
Brief Summary
-----------------
This pilot randomized control trial (RCT) will test a 12-week, multiple behavior intervention physical activity and stress management for survivors with early stage lung cancer (stages I-III) and their family members (1 survivor + 1 family member or friend = 1 dyad). The long-term goal of this research is to improve health outcomes for survivors of lung cancer and their family members. The goals of the intervention, Breathe Easier, are symptom reduction (less breathlessness, less fatigue, less stress) and change in multiple behaviors (increase in stress management and increase in physical activity, and decrease tobacco use - if appropriate). Our aim is: To conduct a 6-month, two-group, pilot randomized control trial intervention study with a pre- and post-test study design to estimate preliminary intervention effects on (a) reduction of symptoms (breathlessness, fatigue, and stress) in survivors of non small cell lung cancer (stages I-III) and family members or friends; (b) increase in physical activity behaviors immediately following the intervention and at 3-months; (c) increase in stress management strategies immediately following the intervention and at 3-months; (d) reduction in smoking behavior among participants who smoke tobacco products at study entry immediately following the intervention at 3-months.

Detailed Description
-----------------
Lung cancer is the second most diagnosed malignancy and the leading cause of cancer deaths, accounting for more annual deaths than breast, prostate, and colorectal cancer combined. Approximately 80% will be diagnosed with NSCLC, and about 42.1% will present with early-stage or localized disease (stages I-III). Improvements in screening and treatment have led to better outcomes for early-stage diagnoses. As early detection improves along with treatments, the current 5-year survival rates (57%, stages I-III; 70%, stage I) are projected to improve. Only a small percentage (5-10%) of patients with lung cancer are asymptomatic at diagnosis. Cough, dyspnea, chest discomfort, and fatigue are common symptoms. Up to 80% of long-term lung cancer survivors report smoking-related comorbidities such as chronic obstructive pulmonary disease (COPD) and heart disease. Thoracic surgery, radiation and chemotherapy may improve or worsen symptoms. After curative surgery, survivors describe persistent physical and psychological symptoms negatively affecting their QOL. The extent of the resection, co-morbid conditions, and smoking status further exacerbate symptoms. Symptoms may be intensified by smoking or withdrawal from tobacco. Nicotine withdrawal brings about a variety of physical and psychological symptoms that can temporarily intensify the symptom burden. Overall, survivors with lung cancer experience more symptom distress than survivors with other types of cancer. Multiple unhealthy behaviors often accompany smoking, including lower physical activity levels and ineffective stress-management skills. Researchers have examined the prevalence of multiple health behaviors in lung cancer survivors; four studies targeted dyads. In one cross-sectional study data from 37 dyads (mostly white, non-Hispanic) showed high rates of smoking (43%, survivors; 30%, family members (FMs)) and physical inactivity (84%, each group). In terms of readiness to change, within 6 months post-diagnosis, 63% of patients and 81% of FMs were ready to increase their physical activity, and 88% of patients and 91% of FMs were prepared to stop smoking. A qualitative study involving 26 African American dyads, within 7 years post-diagnosis, revealed fewer current smokers (15%, survivors; 8% FMs) and persistent physical inactivity (65% survivors; 42% FMs). Two more recent studies collected similar data from survivors and their caregivers (mostly white, non-Hispanic) within 1-month post-diagnosis and 6-months post thoracic surgery reported that survivors and caregivers were receptive to educational and lifestyle behavior modification programs. Evidence strongly suggests that smoking cessation and physical exercise interventions (individually administered) improve QOL and other outcomes; furthermore, exercise therapy is a well-tolerated, safe, and feasible adjunct therapy that can mitigate several diseases- and treatment-related side effects. Mounting evidence suggests that survivors with early-stage lung cancer benefit from regular physical activity. In a study of 175 long-term lung cancer survivors, the 27% who reported meeting physical activity guidelines also reported a higher QOL. Two pilot studies provided proof of principle and showed aerobic training (continuous activity involving large muscle groups) is safe and feasible for survivors of early-stage lung cancer. Thus, it is hoped that this research will advance scientific knowledge about these behaviors being complementary and producing a synergistic effect on behavior change and symptom management. Family, friends, and especially partners of survivors of lung cancer must cope with its physical and psychological impact on the survivor, themselves, and others. It is important to recognize that survivors and their family members react to a serious illness as a unit, and as a result they both have a genuine need for help from healthcare providers. Partners not only provide emotional and practical support, but they must also cope with their own concerns, including the uncertainty surrounding the course of the illness, fear of losing their partner and the impact of their health behaviors. More than half of the partners of lung cancer survivors report negative emotional effects of being the support person. Relationships between survivors and partners are affected by the cancer also. An emerging consensus in the literature is that when both the survivor and family member are treated simultaneously, the well-being of each individual improves. When their needs are not addressed, family members are at risk for impaired health. Interestingly, most health behavior-related interventions focus on an individual's behaviors. Yet, health behaviors tend to cluster in families and social networks. The past decade has seen a growth in interventions exploring the effects of family members (and their behaviors) on each other when a serious illness is diagnosed in one of them. A greater emphasis is needed on interventions that target families, not only the survivor. This proposed research represents the next step toward understanding the best ways to improve multiple behaviors and therefore reduce the burden of symptoms among survivors of lung cancer and their family members. The long-term contribution of this research is to advance scientific knowledge about improving outcomes for the survivors of localized NSCLC (stages I-III) and their family members. Theoretical Framework: Individual and family self-management theory (IFSMT) is a descriptive mid-range theory developed based on conceptual and theoretical perspectives from Systems Theory, Social Learning Theory/Social Cognitive Theory, and Social Support Theory and research related to self-management (SM) of chronic illnesses. IFSMT proposes that successful change in the self-management of behaviors (physical inactivity and stress management) after a diagnosis of lung cancer requires active involvement by the survivor coupled with family support. IFSMT encompasses three broad dimensions: context, process, and outcomes. The context dimension can directly impact individual and family engagement in the self-management process and, therefore, the outcomes. Within the process dimension, self-regulation is the process used to change behavior. Social support enhances the capacity to change and includes influence and collaboration among individuals and family members. In this study, the intervention impacts the self-management process by promoting self-efficacy, self-regulation, and social support; enhancing these three factors, in turn, will lead to improved proximal outcomes (increased stress management and physical activity and reduction in tobacco smoking, relapse prevention) and distal outcomes (reduction of symptoms of dyspnea, fatigue, and stress) for all participants. Design: This study will use a 6-month, longitudinal, two-group, repeated-measures, attention control pilot RCT design. During an enrollment period, the research team will provide information about the study, execute an informed consent process, and collect baseline data. After baseline data is collected, participants will be instructed about the wearing of a wrist accelerometer and responding to Ecological Momentary Assessment (EMA) surveys on their cell phones for a 7-day period prior to randomization. All participants will be instructed on how to keep an accelerometer log and how to respond to mobile EMA surveys. At the end of the 7-day period, accelerometers are returned and completed data is confirmed, the randomization process will take place. The randomization strategy will be determined by the statistician. Based on a grid developed by the statistician each envelope identified by study number only will contain the identification of the study randomized condition (Breathe Easier II [intervention] or attention control. Statistical Analysis As a preliminary step, baseline demographic characteristics and medical histories will be compared between groups (intervention and control), for survivors and family members separately, as well as aggregated across the dyads, using t-tests (for continuous variables) and chi-squared tests (for categorical variables). This is only a preliminary step, dyadic analysis follows. Additionally within-dyad correlations in baseline measures may differ across dyads. For example, whether the association between baseline sleep and physical activity within-dyad differs across pairs. A dyadic analysis will be used as follows: using a series of longitudinal mixed effects models, the effect of intervention vs. control on changes in symptoms (shortness of breath and fatigue) after baseline will be estimated. Specifically, mean symptom at follow-up (end of intervention, 3- and 6-month follow-up) will be simultaneously regressed on group, time, group x time, baseline value, and covariates not balanced by randomization. In addition, models will control for smoking status. Interactions between smoking status at study entry within the intervention group will be explored, as it is hypothesized that the effect of the intervention will be greatest among those who were smoking at study entry. Models will include a subject-specific intercept to adjust for repeated measures of the outcome within participants. Models will be run for the study pool (survivors and family members, considered as dyadic units) with clustering by dyad. This will adjust standard errors for the dependence of outcomes within the dyad by including an interaction term between participant (survivor vs. family member) and treatment group (intervention vs. control). As this is a pilot study, the interest is in estimating effect sizes and corresponding 95% confidence intervals, rather than strict statistical hypothesis testing. Similar analyses will be run to estimate intervention effects on physical activity behavior (exercise capacity, minutes of moderate-intensity activity both objectively measured and self-reported, and sedentary time) and to explore intervention effects on changes in exploratory variables (context and process measures) over time. Finally, using a series of longitudinal regression models implemented with generalized estimating equations with robust standard errors and clustering by dyad, the effect on smoking outcomes at follow-up (abstinence) will be estimated. Specifically, binary indicators of abstinence on treatment assigned (intervention vs. control) and potential covariates (including variables not balanced by randomization) will be regressed using binomial errors, a logit link function, and a working unstructured correlation to accommodate within-subject correlation. Coefficients will be standardized, and models run with the sub-sample of dyads where at least one member smoked at study entry. All models will be run on the intent to treat the sample with all randomized participants included. Changes over time in secondary measured variables (e.g., process measures, sleep) and potential moderators of the intervention effect, will be explored using a similar analytic strategy to that described above. Moderator analyses will be explored by including main effects of the potential moderators (in the model of physical activity behavior for example), as well as the interaction with the treatment group.

Official Title
-----------------
A Dyad-based Multiple Behavior Intervention for Reducing Lung Cancer Symptoms - a Pilot Randomized Control Trial (Breathe Easier II)

Conditions
-----------------
Lung Cancer, Nonsmall Cell, COPD, Self-Management, Physical Inactivity, Stress, Quality of Life

Intervention / Treatment
-----------------
* Behavioral: Breathe Easier


Participation Criteria
=================
Eligibility Criteria
-----------------
Vulnerable populations: Three groups (prisoners, pregnant women and unborn fetuses, and children) will not be included in this study because there may be unknown risks. Prisoners will be excluded because if a survivor or a family member were a current prisoner, it would be impractical to expect an individual to fully participate for 6 months. Pregnant women and unborn fetuses will be excluded because there may be unknown risks. Inclusion of adolescents and children: Adolescents and children will be excluded also because they are younger than the Inclusion Criteria requirement of 21 years of age. Strategies to obtain representation of children in this study would not be appropriate, as they do not get the disease. Also, they will be excluded from participating as family members. Table 3. Inclusion and Exclusion Criteria Inclusion Criteria: Survivors Completed primary treatment for localized NSCLC (stages I-III). Survivors receiving adjuvant therapy are eligible. Willing to use a cell phone capable of receiving text messages Willing to complete a 12-week, home-based intervention program that includes face-to-face and telephone interaction Willing to consider behavior change at this time A family member or friend is willing to participate who is at least 21 years old Able to speak and read English Capable of informed consent A health clearance form is signed by a health care provider prior to enrollment Inclusion Criteria: Family Members or Friends Willing to use a cell phone capable of receiving text messages Willing to complete a 12-week, home-based intervention program that includes face-to-face and telephone interaction Willing to consider behavior change at this time Has an eligible family member willing to participate who is at least 21 years old Able to speak and read English Capable of informed consent A health clearance form signed by a health care provider prior to enrollment Exclusion Criteria: Both A known diagnosis of advanced lung cancer (stage IV) Physical activity is not recommended A history of recurrent falls A substantial mobility impairment related to rheumatoid arthritis, cerebral palsy, muscular dystrophy, multiple sclerosis, paralysis, Parkinson's disease, stroke

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

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A 6-month, two-group, longitudinal pilot RCT study with a pre- and post-test design. The intervention is 12 weeks followed by a 12 week taper. Two groups include an intervention group and an attention control group.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Attention Control<br>Education: Each survivor will receive a copy of Facing Forward; Life After Cancer Treatment (No. 18-2424, March 2018). Each family member or friend will receive When Someone You Love is Being Treated for Cancer (No. 14-5726, May 2014). Specific parts of booklets will be reviewed during the 15-minute/per participant telephone chat. Telephone Chats: The primary purpose is study retention. After the first 12-week period ends the weekly chats will be tapered for 12 weeks. One text message delivered weekly by telephone is a reminder of the day and time of the chat(s). Tobacco Use Reduction: Many survivors of lung cancer struggle with nicotine addiction; smoking cessation and relapse prevention content will be made available to current smokers (The FOREVER FREE program - a free, twelve short booklet evidence-based resource created by the H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida). | Behavioral: Breathe Easier<br>* See Intervention Group (IG) description.<br>|
| Experimental: BE Intervention Group<br>The BE Manual is an educational resource for Managing Stress, Increasing Physical Activity (PA) and Stopping Smoking and Staying Smoke free. A timed, weekly telephone counseling session (60 min./dyad max) will be recorded. The purpose is to provide social support with SMART goal setting, adherence monitoring, encouragement.. Breathing Exercises and Meditations are incorporated into the BE Manual and sent by a link via text messages. A Texting Library provides additional education, support, and encouragement daily. There are 5 story lines: BE Active, BE Kind to Yourself, BE Supportive and BE Smoke free (offered to current smokers only). Stay Smoke free will be instituted once tobacco use has stopped. Weekly Logs for tracking goals and progress with behavior changes (PA, breathing practices and meditations) and a pedometer are provided. After 12 weeks, the calls and texts will be tapered. | Behavioral: Breathe Easier<br>* See Intervention Group (IG) description.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical function behavior change | Measured by self-reported step counting using a pedometer and documented on a daily log. | Daily for 6 months | 
| Physical function behavior change | Objectively measured by wearing an Accelerometer (on the participant's wrist with a velcro band) for 7 days. Measures physical activity intensity (sedentary, light, moderate, vigorous, and very vigorous). | Pre-intervention (Baseline) and post 3-months | 
| Physical function behavior change | Objectively measured by wearing an Accelerometer (on the participant's wrist with a velcro band) for 7 days. Measures physical activity intensity (sedentary, light, moderate, vigorous, and very vigorous). | Pre-intervention (Baseline) and post 6-months | 
| Physical function behavior change | Objectively measured by a Six-minutes Walk Test. Specifically measures physical activity/exercise tolerance. Score = distance traveled in 6 min. measured in meters. | Pre-intervention (Baseline) and post 3-months | 
| Physical function behavior change | Objectively measured by a Six-minutes Walk Test. Specifically measures physical activity/exercise tolerance. Score = distance traveled in 6 min. measured in meters. | Pre-intervention (Baseline) and post 6-months | 
| Stress management behavior change | Measured by self-reported practice of breathing exercises documented on daily logs. | Daily for 6 months | 
| Stress management behavior change | Measured by self-reported meditation practice documented on daily logs. | Daily for 6 months | 
| Change in the symptom of dyspnea | As measured by a validated instrument: Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea Short Form (Part 1) Measured by 10 items with a 4-point rating scale measuring shortness of breath (SOB) over the past 7 days (0 = not SOB; 1 = mildly SOB; 2= moderately SOB; 3 = severe SOB). Total score range 0 to 40. The higher the score measures worse SOB. | Pre-intervention (Baseline) and post 3-months | 
| Change in the symptom of dyspnea | As measured by a validated instrument: Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea Short Form (Part 1) Measured by 10 items with a 4-point rating scale measuring shortness of breath (SOB) over the past 7 days (0 = not SOB; 1 = mildly SOB; 2= moderately SOB; 3 = severe SOB). Total score range 0 to 40. The higher the score measures worse SOB. | Pre-intervention (Baseline) and post 6-months | 
| Change in the symptom of dyspnea | As measured by a validated instrument: Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea Short Form (Part 2). Measured by 10 items with a 4-point rating scale measuring functional limitations due to shortness of breath (SOB) over the past 7 days (0 = no difficulty, 1 = little difficulty; 2= some difficulty; 3 = much difficulty). Total score range 0 to 40. The higher the score measures greater functional difficulty due to SOB. | Pre-intervention (Baseline) and post 3-months | 
| Change in the symptom of dyspnea | As measured by a validated instrument: Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea Short Form (Part 2). Measured by 10 items with a 4-point rating scale measuring functional limitations due to shortness of breath (SOB) over the past 7 days (0 = no difficulty, 1 = little difficulty; 2= some difficulty; 3 = much difficulty). Total score range 0 to 40. The higher the score measures greater functional difficulty due to SOB. | Pre-intervention (Baseline) and post 6-months | 
| Change in the symptom of breathlessness | As measured by validated instrument: Modified Medical Research Council - Dyspnea (mMRC) measures respiratory disability. 1 item measures perceived breathlessness. There are 5 statements describing respiratory disability. Scores range from 1 to 5. No disability = I only get breathless with strenuous exercise (Grade 1) to I am too breathless to leave the house (Grade 5). The higher the score the greater the disability. | Pre-intervention (Baseline) and post 3-months | 
| Change in the symptom of breathlessness | As measured by validated instrument: Modified Medical Research Council - Dyspnea (mMRC) measures respiratory disability. 1 item measures perceived breathlessness. There are 5 statements describing respiratory disability. Scores range from 1 to 5. No disability = I only get breathless with strenuous exercise (Grade 1) to I am too breathless to leave the house (Grade 5). The higher the score the greater the disability. | Pre-intervention (Baseline) and post 6-months | 
| Change in the symptom of fatigue | As measured by a validated instrument: Functional Assessment of Chronic Illness Therapy Scale (FACIT)-Fatigue (V.4) measures fatigue. Measured by 13-items with a 4-point rating scale (4 = not fatigued at all; 0 = very much fatigued). Score range is 6 to 52. The higher the score the less fatigue. | Pre-intervention (Baseline) and post 3-months | 
| Change in the symptom of fatigue | As measured by a validated instrument: Functional Assessment of Chronic Illness Therapy Scale (FACIT)-Fatigue (V.4) measures fatigue. Measured by 13-items with a 4-point rating scale (4 = not fatigued at all; 0 = very much fatigued). Score range is 6 to 52. The higher the score the less fatigue. | Pre-intervention (Baseline) and post 6-months | 
| Change in perceived stress | As measured by a validated instrument: Perceived Stress Scale measures perceived stress using a 10-item scale. There are 5 response items (0 = never, 1 = almost never, 2 = sometimes, 3 = fairly often, 4 = very often). Score ranges from 0 to 40. The higher the score the greater perceived stress. | Pre-intervention (Baseline) and post 3-months | 
| Change in perceived stress | As measured by a validated instrument: Perceived Stress Scale measures perceived stress using a 10-item scale. There are 5 response items (0 = never, 1 = almost never, 2 = sometimes, 3 = fairly often, 4 = very often). Score ranges from 0 to 40. The higher the score the greater perceived stress. | Pre-intervention (Baseline) and post 6-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tobacco use abstinence | Abstinence since quit date (score options yes/no) | Pre-intervention (Baseline) and post 3-months | 
| Tobacco use abstinence | Abstinence since quit date (score options yes/no) | Pre-intervention (Baseline) and post 6-months | 
| Tobacco use abstinence | Number of days without smoking in previous 7 days (score options: 0 to 7 days) will be measured by self report. The greater the number the greater daily abstinence. | Pre-intervention (Baseline) and post 3-month | 
| Tobacco use abstinence | Number of days without smoking in previous 7 days (score options: 0 to 7 days) will be measured by self report. The greater the number the greater daily abstinence. | Pre-intervention (Baseline) and post 6-months | 
| Tobacco use abstinence | Saliva cotinine analysis: immune-chromatographic assay that quantifies cotinine (a major metabolite of nicotine with a relatively long half-life [10-40 hr]) will verify tobacco abstinence. Results will be reported as ___ng/ml. Result interpretations will be guided by https://salimetrics.com/guidelines-for-interpreting-cotinine-levels-united-states. | Pre-intervention (Baseline) and post 3-months | 
| Tobacco use abstinence | Saliva cotinine analysis: immune-chromatographic assay that quantifies cotinine (a major metabolite of nicotine with a relatively long half-life [10-40 hr]) will verify tobacco abstinence. Results will be reported as ___ng/ml. Result interpretations will be guided by https://salimetrics.com/guidelines-for-interpreting-cotinine-levels-united-states. | Pre-intervention (Baseline) and post 6-months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer Survivorship