Brief Behavioral Therapy in Improving Sleep Disorders in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

Study Overview
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Brief Summary
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This randomized phase II trial studies how well brief behavioral therapy works in improving sleep disorders in patients with stage I-III breast cancer undergoing chemotherapy. Sleep disorder counseling may reduce fatigue and insomnia as well as improve the well-being and quality of life in patients with breast cancer who are undergoing chemotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine recruitment rates to the proposed randomized controlled trial (RCT). II. Determine the rate of intervention adherence. III. Determine the feasibility of training National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical research staff to successfully deliver the Brief Behavioral Therapy (BBT) intervention. SECONDARY OBJECTIVES: I. Obtain preliminary estimates for the effect of the intervention (compared with control) on insomnia as measured by the Insomnia Severity Index (ISI). II. Obtain preliminary estimates for the effect of the intervention (compared with control) on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). III. Obtain preliminary estimates for the effect of the intervention (compared with control) on circadian rhythm as measured by the two-oscillator cosinor parameter estimates based on actigraphy data. IV. Obtain preliminary estimates for the effect of the intervention (compared with control) on heart rate variability (HRV) as measured by the Firstbeat® ambulatory heart-rate monitor (i.e., 1. respiratory sinus arrhythmia-RSA, 2. standard deviation of all normal R-wave to R-wave intervals--SDNN, 3. root mean square of successive differences between adjacent normal R-wave to R-wave intervals--RMSSD, 4. The ratio of low frequency total spectrum power of all NN intervals between .04 to .15 Hertz to high frequency total spectrum power of all NN intervals between .15 to .40 Hertz--LF/HF ratio, and 5. natural log of low frequency total spectrum power of all NN intervals between 0.04 to 0.15Hz.). TERTIARY OBJECTIVES: I. Obtain preliminary estimates for the effect of the intervention (compared with control) on quality of life as measured by the Functional Assessment of Chronic Illness Therapy (FACIT) total score and subscales. II. Obtain preliminary estimates for the effect of the intervention (compared with control) on general mood as measured by the Profile of Mood States (POMS) total score and subscales. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo BBT intervention, comprising insomnia education, stimulus control, discouragement of napping and encouragement of exercise, and sleep compression over two 60 minute face-to-face sessions in weeks 1 and 3 or 4, and four 15 minute telephone sessions in weeks 2, 3, 5, and 6 or 2, 4, 5, and 6. ARM II: Patients undergo Healthy Eating Education (HEAL) comprising nutritional education and suggestions for symptom management over two 60 minute face-to-face sessions in weeks 1 and 2 or 3, and four 15 minute telephone sessions in weeks 2, 3, 5, and 6 or 2, 4, 5, and 6. After completion of study, patients are followed up at 1 month.

Official Title
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Feasibility, Acceptability and Mechanisms of Brief Behavioral Therapy (BBT) for Sleep Problems During Chemotherapy: A Phase II Randomized Controlled Trial

Conditions
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Sleep Disorder, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Intervention / Treatment
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* Behavioral: Brief Behavioral Therapy
* Behavioral: Telephone-Based Intervention
* Other: Educational Intervention
* Behavioral: Telephone-Based Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed breast cancer (stage I, II, III) Be receiving chemotherapy in either weekly, 2-week or 3-week cycles and have at least 6 weeks of chemotherapy treatment remaining; patients are eligible any time before chemotherapy cycle 3 if on a 2- or 3-week cycle, or cycle 4 if on a 1-week cycle; (Note: use of biologics [e.g., Herceptin (trastuzumab)] is permitted) For patients on a weekly regimen, there should be at least 3 dosages of chemotherapy remaining For patients on either a 2 week or 3 week cycle, there should be at least 2 dosages of chemotherapy remaining Patients will not be dropped from the study if their chemotherapy is discontinued after they are enrolled Report sleep disturbance of 8 (sum total of all 7 items) or greater on the Insomnia Severity Index (Note: this measure will be repeated again at baseline assessment) Report sleep problems that began or got worse with the diagnosis of cancer or with chemotherapy; (did your sleep problems begin or get worse with the diagnosis of cancer or with chemotherapy?) Be able to speak and read English Patients can take sleep aids (e.g., hypnotics and sedatives) for insomnia if they use sleep aids as needed; patients taking sleep aids every night are excluded; use of melatonin every night is permitted and these patients are not excluded Be able and willing to wear an Actiwatch for the entire 24 hours of each day they are scheduled to wear it Exclusion Criteria: Have diagnosis of breast cancer stage IV Have sleep problems that began before diagnosis and have not changed since diagnosis Self-report or have a medical record of an unstable comorbid medical or psychiatric condition that would make it unsafe or impossible to adhere to the study protocol Have a clinical diagnosis of sleep apnea or restless leg syndrome Be unable or unwilling to discontinue anxiolytic medication within 4 hours of intervention sessions Take medication for sleep (e.g., hypnotics and sedatives) every night; melatonin is permitted Patients who are shift workers are excluded; shift worker is defined as someone who has irregular work and sleep hours (such as working a non-traditional schedule: e.g., 4pm-midnight or 10pm-6am; a rotating schedule e.g., alternating between day and night shifts, or starting work between 4am and 7am) Have an implanted device for heart failure (e.g., pacemaker, defibrillator, left ventricular assist device, etc.)

Ages Eligible for Study
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Minimum Age: 21 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (BBT intervention)<br>Patients undergo BBT intervention, comprising insomnia education, stimulus control, discouragement of napping and encouragement of exercise, and sleep compression over two 60 minute face-to-face sessions in weeks 1 and 3 or 4, and four 15 minute telephone sessions in weeks 2, 3, 5, and 6 or 2, 4, 5, and 6. | Behavioral: Brief Behavioral Therapy<br>* Undergo BBT intervention<br>* Other names: Behavioral Interventions;Behavioral: Telephone-Based Intervention<br>* Undergo BBT intervention<br>|
| Active Comparator: Arm II (control)<br>Patients undergo HEAL comprising nutritional education and suggestions for symptom management over two 60 minute face-to-face sessions in weeks 1 and 3 or 4, and four 15 minute telephone sessions in weeks 2, 3, 5, and 6 or 2, 4, 5, and 6. | Other: Educational Intervention<br>* Undergo HEAL<br>* Other names: Intervention, Educational;Behavioral: Telephone-Based Intervention<br>* Undergo HEAL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Eligible Patients Consented | Will be evaluated by calculating the specific percentage (with 95% confidence interval) of the total number of participants approached that then consented and enrolled in the study. | baseline | 
| Percentage of Consented Participants Who Complete the Study, Defined as Completion of at Least 5 BBT | Will be evaluated by calculating the specific percentage (with 95% confidence interval) and performing an exact binomial test with the null hypothesis being greater than or equal to 75%. | Up to 1 month | 
| Percentage of Key Components of BBT Delivered by NCI Community Oncology Research Program (NCORP) Staff, Assessed by Checklist and Auditing of Audio-recordings | Each NCORP staff person completed a study checklist in which they designated which concepts they discussed with the patient at each session. Concepts included how sleep problems develped, how to control stimulus, and sleeping environment. The overall mean percent delivery was measured using a random effects model (residual maximum likelihood [REML] estimation), where the intercept represents the mean delivery and three independent random effects are included. Because of the small sample size, testing will use the Kenward-Roger procedure. | Up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insomnia as Measured by the Insomnia Severity Index (ISI) | The ISI has seven questions. The seven answers are added up to get a total score. Total score categories: 0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate severity) 22-28 = Clinical insomnia (severe) The difference between arms will be assessed using analysis of covariance (ANCOVA). The response will be the post-intervention outcome. Arm will be the factor, and baseline will be the covariate. Appropriate contrasts will be used to estimate the difference between arms in change from baseline. Initially, the arm*baseline interaction will be assessed with an F test. If this interaction is insignificant at the 0.05 level, it will be dropped from the final model. If the interaction is significant, then mean change from baseline at various levels of baseline will be reported. | Baseline to up to 1 month | 
| Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. The difference between arms will be assessed using ANCOVA. The response will be the post-intervention outcome. Arm will be the factor, and baseline will be the covariate. Appropriate contrasts will be used to estimate the difference between arms in change from baseline. Initially, the arm*baseline interaction will be assessed with an F test. If this interaction is insignificant at the 0.05 level, it will be dropped from the final model. If the interaction is significant, then mean change from baseline at various levels of baseline will be reported. | Baseline to up to 1 month | 
| Change in Mean Circadian Rhythm Mesor | Activity levels were measured using an actigraphy device worn as a watch. The data was collected by the device for a 24 hour period. A model consisting of two cosine functions, one with a period of 12 hours, and the other with a period of 24 hours is fit to log activity counts as the dependent variable, and hour (0 to 24) as the independent variable. The mesor is the average activity over a 24 hour period. | Baseline to up to 1 month | 
| Change in Circadian Rhythm Amplitude Over 24 Hours | Activity levels were measured using an actigraphy device worn as a watch. The data was collected by the device for a 24 hour period. A model consisting of two cosine functions, one with a period of 12 hours, and the other with a period of 24 hours is fit to log activity counts as the dependent variable, and hour (0 to 24) as the independent variable. The ampliitude is the peak activity level over a 24 hour period. | baseline to up to 1 month | 
| Change in Circadian Rhythm Amplitude Over 12 Hours | Activity levels were measured using an actigraphy device worn as a watch. The data was collected by the device for a 24 hour period. A model consisting of two cosine functions, one with a period of 12 hours, and the other with a period of 24 hours is fit to log activity counts as the dependent variable, and hour (0 to 24) as the independent variable. The amplitude is the highest activity level over a 12 hour period. | baseline to up to 1 month | 
| Change in Mean Circadian Rhythm Acrophase Over 24 Hours | Activity levels were measured using an actigraphy device worn as a watch. The data was collected by the device for a 24 hour period. A model consisting of two cosine functions, one with a period of 12 hours, and the other with a period of 24 hours is fit to log activity counts as the dependent variable, and hour (0 to 24) as the independent variable. The acrophase is the time where peak activity occurs over a 24 hour period. The larger the acrophase the later in the day is the peak activity. | baseline to up to 1 month | 
| Change in Mean Circadian Rhythm Acrophase Over 12 Hours | Activity levels were measured using an actigraphy device worn as a watch. The data was collected by the device for a 24 hour period. A model consisting of two cosine functions, one with a period of 12 hours, and the other with a period of 24 hours is fit to log activity counts as the dependent variable, and hour (0 to 24) as the independent variable. The acrophase is the time where peak activity occurs over a 12 hour period. The larger the acrophase the later in the day is the peak activity. | baseline to up to 1 month |