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

• Sponsor: Gary Morrow (Other)
• Overall Status: Completed
• CT.gov ID: NCT02002533
• Collaborator: National Cancer Institute (NCI) (NIH), Stanford University (Other)
• Enrollment: 71
• Locations: 6
• Arms: 2
• Actual Duration (Months): 34.4
• Patients Per Site: 11.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Behavioral: Brief Behavioral Therapy; Behavioral: Telephone-Based Intervention; Other: Educational Intervention; Behavioral: Telephone-Based Intervention	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. Determine recruitment rates to the proposed randomized controlled trial (RCT).

2. 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:

1. Obtain preliminary estimates for the effect of the intervention (compared with control) on insomnia as measured by the Insomnia Severity Index (ISI).

2. Obtain preliminary estimates for the effect of the intervention (compared with control) on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI).

3. 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.

4. 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:

1. 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.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Feasibility, Acceptability and Mechanisms of Brief Behavioral Therapy (BBT) for Sleep Problems During Chemotherapy: A Phase II Randomized Controlled Trial
• Actual Study Start Date: Feb 3, 2014
• Actual Primary Completion Date: Dec 16, 2016
• Actual Study Completion Date: Dec 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Behavioral: Brief Behavioral Therapy; Undergo BBT intervention; Other Names: Behavior Conditioning Therapy Behavior Modification Behavior or Life Style Modifications Behavior Therapy Behavioral Interventions ; Behavioral: Telephone-Based Intervention; Undergo BBT intervention
Active Comparator: 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.	Other: Educational Intervention; Undergo HEAL; Other Names: Education for Intervention Intervention, Educational ; Behavioral: Telephone-Based Intervention; Undergo HEAL

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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%.

3. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305
2	Heartland NCORP	Decatur	Illinois	United States	62526
3	Wichita NCORP	Wichita	Kansas	United States	67214
4	Metro-Minnesota NCORP	Minneapolis	Minnesota	United States	55426
5	University of Rochester	Rochester	New York	United States	14642
6	Southeast Clinical Oncology Research Program	Winston-Salem	North Carolina	United States	27104

Sponsors and Collaborators

• Gary Morrow
• National Cancer Institute (NCI)
• Stanford University

Investigators

• Principal Investigator: Oxana Palesh, University of Rochester NCORP Research Base

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary Morrow, Director, University of Rochester NCORP Research Base
• ClinicalTrials.gov Identifier: NCT02002533
• Other Study ID Numbers: URCC12048; NCI-2013-01170; URCC12048; URCC-12048; URCC12048; UG1CA189961; U10CA037420
• First Posted: Dec 6, 2013
• Last Update Posted: Jun 5, 2019
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Breast Neoplasms; Sleep Wake Disorders; Parasomnias

Study Results

Participant Flow

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	34	37
COMPLETED	28	19
NOT COMPLETED	6	18

Baseline Characteristics

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	34	37	71
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	50.9	53.9	52.5
Sex: Female, Male (Count of Participants)
Female	34 100%	37 100%	71 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	34 100%	37 100%	71 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.7%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 2.9%	1 2.7%	2 2.8%
White	33 97.1%	35 94.6%	68 95.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	34 100%	37 100%	71 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Eligible Patients Consented
Description	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

Outcome Measure Data

Analysis Population Description

92 people were approached to enroll in the study

Arm/Group Title	All Participants
Arm/Group Description	All people that were enrolled in the study regardless of intervention assigned.
Measure Participants	92
Number (95% Confidence Interval) [percentage of participants]	77.17 227%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	exact binomial test
	Comments	The percentage is greater than or equal to 40%.

2. Primary Outcome

Title	Percentage of Consented Participants Who Complete the Study, Defined as Completion of at Least 5 BBT
Description	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

Outcome Measure Data

Analysis Population Description

Data on HEAL subjects was not collected since the main focus was BBT, therefore only rate of adherence is shown for BBT group.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	34	0
Number (95% Confidence Interval) [percentage of participants]	73.5 216.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7350
	Comments
	Method	exact binomial test
	Comments

3. Primary Outcome

Title	Percentage of Key Components of BBT Delivered by NCI Community Oncology Research Program (NCORP) Staff, Assessed by Checklist and Auditing of Audio-recordings
Description	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

Outcome Measure Data

Analysis Population Description

This assessment was only performed for the BBT arm.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	34	0
Mean (Standard Error) [percentage of components delivered]	0.8075 (0.08450)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8075
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08450
	Estimation Comments

4. Secondary Outcome

Title	Change in Insomnia as Measured by the Insomnia Severity Index (ISI)
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [units on a scale]	-6.259 (5.134)	-2.450 (6.700)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1808
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.64
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.21
	Estimation Comments	The estimated value is BBT minus HEAL.

5. Secondary Outcome

Title	Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI)
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [units on a scale]	-4.000 (3.590)	-2.750 (4.089)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.08
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	Estimation Comments	Estimated value is BBT minus HEAL.

6. Secondary Outcome

Title	Change in Mean Circadian Rhythm Mesor
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [log activity counts]	0.008 (0.153)	-0.046 (0.156)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments	For baseline of 0.7.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.404
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.137
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments	At baseline 1.3.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.077
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.045
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.556
	Comments	At baseline of 1.5.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.032
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.053
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	Grouped by baseline interaction.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.24
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.221
	Estimation Comments	The estimated value is grouped by baseline interaction parameter.

7. Secondary Outcome

Title	Change in Circadian Rhythm Amplitude Over 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [log10 (counts/minute)]	0.061 (0.185)	-0.164 (0.194)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Change in Circadian Rhythm Amplitude Over 12 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [log10 (counts/minute)]	0.063 (0.164)	0.127 (0.236)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.295
	Comments
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Change in Mean Circadian Rhythm Acrophase Over 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [hours]	0.409 (3.698)	-0.912 (2.855)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.573
	Comments
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Change in Mean Circadian Rhythm Acrophase Over 12 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Based on subjects that completed study through post-intervention.

Arm/Group Title	Arm I (BBT Intervention)	Arm II (Control)
Arm/Group Description	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	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
Measure Participants	28	19
Mean (Standard Deviation) [hours]	0.529 (2.519)	1.516 (4.833)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.502
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.558
	Estimation Comments	Group difference (BBT - HEAL) in mean post-pre change.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.094
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.723
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.007
	Estimation Comments	Group difference (BBT - HEAL) in mean post-pre change.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.114
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.750
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.326
	Estimation Comments	Group difference (BBT - HEAL) in mean post-pre change.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	All Participants, Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.911
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.400
	Estimation Comments	This is an arm by baseline interaction parameter.

Adverse Events

Arm/Group Title	Arm I (BBT Intervention)		Arm II (Control)
Arm/Group Description	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		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
All Cause Mortality
	Arm I (BBT Intervention)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (BBT Intervention)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (BBT Intervention)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		3/37 (8.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/34 (0%)	0	3/37 (8.1%)	3
Anemia	0/34 (0%)	0	1/37 (2.7%)	1
Gastrointestinal disorders
mucositis stomastitis	0/34 (0%)	0	1/37 (2.7%)	1
Metabolism and nutrition disorders
hypophosphatemia	0/34 (0%)	0	1/37 (2.7%)	1
Nervous system disorders
Headache	0/34 (0%)	0	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Sore Throat	0/34 (0%)	0	1/37 (2.7%)	1
Vascular disorders
hypotension	0/34 (0%)	0	1/37 (2.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.