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
Conditions
Brief summary
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
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.
Interventions
BEHAVIORALBrief Behavioral Therapy
Undergo BBT intervention
BEHAVIORALTelephone-Based Intervention
Undergo BBT intervention
OTHEREducational Intervention
Undergo HEAL
Sponsors
National Cancer Institute (NCI)
Stanford University
Gary Morrow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Eligible Patients Consented | baseline | 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. |
| Percentage of Consented Participants Who Complete the Study, Defined as Completion of at Least 5 BBT | Up to 1 month | 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%. |
| Percentage of Key Components of BBT Delivered by NCI Community Oncology Research Program (NCORP) Staff, Assessed by Checklist and Auditing of Audio-recordings | Up to 1 month | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Circadian Rhythm Amplitude Over 24 Hours | baseline to up to 1 month | 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. |
| Change in Circadian Rhythm Amplitude Over 12 Hours | baseline to up to 1 month | 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. |
| Change in Insomnia as Measured by the Insomnia Severity Index (ISI) | Baseline to up to 1 month | 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. |
| Change in Mean Circadian Rhythm Acrophase Over 12 Hours | baseline to up to 1 month | 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. |
| Change in Mean Circadian Rhythm Acrophase Over 24 Hours | baseline to up to 1 month | 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. |
| Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Baseline to up to 1 month | 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. |
| Change in Mean Circadian Rhythm Mesor | Baseline to up to 1 month | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (BBT Intervention) 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.
Brief Behavioral Therapy: Undergo BBT intervention
Telephone-Based Intervention: Undergo BBT intervention | 34 |
| Arm II (Control) 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.
Educational Intervention: Undergo HEAL
Telephone-Based Intervention: Undergo HEAL | 37 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 13 |
Baseline characteristics
| Characteristic | Arm I (BBT Intervention) | Total | Arm II (Control) |
|---|---|---|---|
| Age, Continuous | 50.9 years | 52.5 years | 53.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 71 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 68 Participants | 35 Participants |
| Region of Enrollment United States | 34 Participants | 71 Participants | 37 Participants |
| Sex: Female, Male Female | 34 Participants | 71 Participants | 37 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 3 / 37 |
| serious Total, serious adverse events | 0 / 34 | 0 / 37 |
Outcome results
Primary
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%.
Time frame: Up to 1 month
Population: Data on HEAL subjects was not collected since the main focus was BBT, therefore only rate of adherence is shown for BBT group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Consented Participants Who Complete the Study, Defined as Completion of at Least 5 BBT | 73.5 percentage of participants |
p-value: 0.735exact binomial test
Primary
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.
Time frame: baseline
Population: 92 people were approached to enroll in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Eligible Patients Consented | 77.17 percentage of participants |
p-value: >0.9999exact binomial test
Primary
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.
Time frame: Up to 1 month
Population: This assessment was only performed for the BBT arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Percentage of Key Components of BBT Delivered by NCI Community Oncology Research Program (NCORP) Staff, Assessed by Checklist and Auditing of Audio-recordings | 0.8075 percentage of components delivered | Standard Error 0.0845 |
p-value: <0.0001Mixed Models Analysis
Secondary
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.
Time frame: baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Circadian Rhythm Amplitude Over 12 Hours | 0.063 log10 (counts/minute) | Standard Deviation 0.164 |
| Arm II (Control) | Change in Circadian Rhythm Amplitude Over 12 Hours | 0.127 log10 (counts/minute) | Standard Deviation 0.236 |
p-value: 0.295ANCOVA
Secondary
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.
Time frame: baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Circadian Rhythm Amplitude Over 24 Hours | 0.061 log10 (counts/minute) | Standard Deviation 0.185 |
| Arm II (Control) | Change in Circadian Rhythm Amplitude Over 24 Hours | -0.164 log10 (counts/minute) | Standard Deviation 0.194 |
p-value: 0ANCOVA
Secondary
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.
Time frame: Baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Insomnia as Measured by the Insomnia Severity Index (ISI) | -6.259 units on a scale | Standard Deviation 5.134 |
| Arm II (Control) | Change in Insomnia as Measured by the Insomnia Severity Index (ISI) | -2.450 units on a scale | Standard Deviation 6.7 |
p-value: 0.1808ANCOVA
Secondary
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.
Time frame: baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Mean Circadian Rhythm Acrophase Over 12 Hours | 0.529 hours | Standard Deviation 2.519 |
| Arm II (Control) | Change in Mean Circadian Rhythm Acrophase Over 12 Hours | 1.516 hours | Standard Deviation 4.833 |
p-value: 0.015ANCOVA
p-value: 0.094ANCOVA
p-value: 0.114ANCOVA
p-value: 0.027ANCOVA
Secondary
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.
Time frame: baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Mean Circadian Rhythm Acrophase Over 24 Hours | 0.409 hours | Standard Deviation 3.698 |
| Arm II (Control) | Change in Mean Circadian Rhythm Acrophase Over 24 Hours | -0.912 hours | Standard Deviation 2.855 |
p-value: 0.573ANCOVA
Secondary
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.
Time frame: Baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Mean Circadian Rhythm Mesor | 0.008 log activity counts | Standard Deviation 0.153 |
| Arm II (Control) | Change in Mean Circadian Rhythm Mesor | -0.046 log activity counts | Standard Deviation 0.156 |
p-value: 0.005ANCOVA
p-value: 0.092ANCOVA
p-value: 0.556ANCOVA
p-value: 0.007ANCOVA
Secondary
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.
Time frame: Baseline to up to 1 month
Population: Based on subjects that completed study through post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | -4.000 units on a scale | Standard Deviation 3.59 |
| Arm II (Control) | Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) | -2.750 units on a scale | Standard Deviation 4.089 |
p-value: 0.14ANCOVA