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Trial registered on ANZCTR


Registration number
ACTRN12618001255279
Ethics application status
Approved
Date submitted
23/07/2018
Date registered
25/07/2018
Date last updated
20/11/2019
Date data sharing statement initially provided
16/09/2019
Date results information initially provided
20/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Sleepwell: A Trial to Improve Sleep During Chemotherapy for Breast Cancer
Scientific title
Light Enhanced Cognitive Behavioural Therapy (CBT+) for Sleep and Fatigue: A Randomized Controlled Trial during Chemotherapy for Breast Cancer
Secondary ID [1] 295633 0
None
Universal Trial Number (UTN)
U1111-1217-9000
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer 308966 0
sleep disruption 308968 0
Condition category
Condition code
Cancer 307866 307866 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CBT+ Intervention
The intervention was designed to deliver effective results whilst being as least burdensome as possible. Given that women with breast cancer are already subjected to an intensive treatment regimen, the design of the intervention was carefully considered such that the effort and time associated with each intervention component are outweighed by the likely physical and psychological benefits. The face-to-face session will be scheduled around participants’ existing appointments at the Peter MacCallum Cancer Centre to reduce burden of time and travel. All other aspects of the intervention can be completed in the comfort of participants’ own homes, at their leisure. The light glasses are comfortable, easy to wear, and are not likely to disrupt participant’s usual morning routines. Wearing the light glasses will not impair participants’ ability to move around and undertake any domestic or work related responsibilities such as preparing and consuming food, household cleaning, reading, writing or typing. Furthermore, the intervention is also economical from the perspective of the healthcare system, it is simple for clinicians to deliver and entails minimal financial expense and burden of time. These are important considerations when evaluating whether the intervention, if effective, could be implemented into routine care.
In this study, the intervention will be delivered by a provisional psychologist who has received specialist training in cognitive behavioral therapy for sleep.
Cognitive Behavioural Therapy
Those participants allocated to the intervention group will receive ‘cognitive behavioural and bright therapy’ (CBT+). CBT+ is delivered via one 75-minute face to face session, one phone call lasting approximately 30 minutes and a series of 7 emails, one per week, that take approximately 15-20 minutes to read. Generally, the intervention group will receive sleep strategies with the following core components:
• general information and skills for better sleep (e.g., sleep hygiene, relaxation and mindfulness exercises, dealing with nighttime worries);
• fostering healthy attitudes and expectations about sleep following cancer diagnosis and during treatment;
• managing sleep challenges specific to cancer patients (e.g., physical discomfort, pain, daytime consequences of poor sleep);
• identifying and managing symptoms of insomnia (e.g., self-monitoring, stimulus control, sleep scheduling, bed restriction).
The intervention materials for the CBT+ component were adapted from the Cognitive Behavioural Treatment of Insomnia Session by Session Guide (Perlis, Jungquist, Smith & Posner, 2005). This adapted version of CBT-I is designed to maximise treatment outcomes whilst promoting sustainable integration with current oncological care at the VCCC.
Bright Light Therapy Individualised Protocol
The light therapy component will consist of daily light glasses use for the six-week duration of the intervention. Participants will receive a pair of Luminette light glasses to take home with them during the face to face CBT-I session and will be instructed to wear them for 30 minutes upon awakening each morning. Specific timing of light glasses use will be established individually with each participant during the face-to-face session.
This guide will cover key components when discussing light and dark therapy with participants during the face to face session. The goals are to:
• assess current sleep/wake patterns and individualise light/dark exposure;
• explain the functions of light therapy so participants understand how to apply strategies in their daily experiences; and
• discuss potential barriers to using light glasses and engaging in light therapy more generally, collaboratively brainstorming solutions.
Note: Participants with very advanced (habitual bedtime before 8am and risetime before 4am)/delayed sleep timing (habitual bedtime after 3am and risetime after 11am), or have irregular or non-24 sleep/wake patterns are excluded based on the Duke interview.
Participants will be asked to wear a wrist-worn watch-like device throughout the entirety of the intervention to objectively measure sleep.
Adherence will be assessed by: accessing read and click information from emails including a comprehension check question included in each email and daily reports of the time and duration light glasses were worn.
Intervention code [1] 301948 0
Behaviour
Comparator / control treatment
Control Intervention
The control group will receive two emails containing web links to relaxation audio tracks. These emails will be received during the first and third week of the intervention. The first relaxation audio consists of abdominal breathing strategies that may assist in calming the mind and relaxing the body. The second audio consist of a body scan relaxation, both audio tracks are approximately 15 minutes and participants are instructed to listen to these audio tracks each day, whenever they feel they might be beneficial. These relaxation tracks were developed by the cancer council to assist patients in coping with a cancer diagnosis. The relaxation audio tracks do not contain any sleep specific information, instead, they include general relaxation strategies that can be used by participants at any time during the day or night. The control group will also receive a brief phone call (15 minutes) during the fourth week of their study involvement to check in with participants’ and respond to any queries or complaints. The phone call will be delivered by a provisional psychologist who has received specialist training in sleep.
Following the final follow-up assessment, the control group will receive the set of CBT+ email packages, an additional information booklet detailing the contents of the face-to-face session and an information booklet on light therapy.
Participants will be asked to wear a wrist-worn watch-like device throughout the entirety of the intervention to objectively measure sleep.
Adherence will be assessed by: accessing read and click information from emails.
Control group
Active

Outcomes
Primary outcome [1] 306840 0
Symptoms of insomnia assessed via the Insomnia Severity Index (ISI; Bastien, Vallières, & Morin, 2001).
Timepoint [1] 306840 0
Baseline (Week 0), Midpoint (Week 3), Post-Treatment (Week 6), and Follow-Up (3 months), used to estimate slopes over time. There is no single primary timepoint as we are using the change over time in outcome to define the success/failure of the trial.
Primary outcome [2] 306841 0
Sleep Diary - Sleep Efficiency
Timepoint [2] 306841 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time. There is no single primary timepoint as we are using the change over time in outcome to define the success/failure of the trial.
Secondary outcome [1] 349888 0
Sleep Diary – Sleep Onset Latency
Timepoint [1] 349888 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time.
Secondary outcome [2] 349889 0
Sleep Diary - Wake After Sleep Onset
Timepoint [2] 349889 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time.
Secondary outcome [3] 349890 0
Sleep Diary - Total Sleep Time
Timepoint [3] 349890 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time.
Secondary outcome [4] 349891 0
Actigraphy - Sleep Efficiency
Timepoint [4] 349891 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time.
Secondary outcome [5] 349894 0
Actigraphy - Wake After Sleep Onset
Timepoint [5] 349894 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time.
Secondary outcome [6] 349895 0
Actigraphy - Total Sleep Time
Timepoint [6] 349895 0
Continuously assessed over the 6 weeks of the trial and used to estimate slopes over time.
Secondary outcome [7] 349896 0
PROMIS Sleep Related Impairment - 8 item SFa
Timepoint [7] 349896 0
Baseline (Week 0), Midpoint (Week 3), Post-Treatment (Week 6), and Follow-Up (3 months), used to estimate slopes over time.
Secondary outcome [8] 349897 0
PROMIS Sleep Disturbance - 8 item SFa
Timepoint [8] 349897 0
Baseline (Week 0), Midpoint (Week 3), Post-Treatment (Week 6), and Follow-Up (3 months), used to estimate slopes over time.
Secondary outcome [9] 349898 0
PROMIS Fatigue - 8 item SFa
Timepoint [9] 349898 0
Baseline (Week 0), Midpoint (Week 3), Post-Treatment (Week 6), and Follow-Up (3 months), used to estimate slopes over time.
Secondary outcome [10] 349899 0
PROMIS Depression - 8 item SFa
Timepoint [10] 349899 0
Baseline (Week 0), Midpoint (Week 3), Post-Treatment (Week 6), and Follow-Up (3 months), used to estimate slopes over time.
Secondary outcome [11] 349900 0
PROMIS Anxiety - 8 item SFa
Timepoint [11] 349900 0
Baseline (Week 0), Midpoint (Week 3), Post-Treatment (Week 6), and Follow-Up (3 months), used to estimate slopes over time.

Eligibility
Key inclusion criteria
Inclusion criteria include:
1. Diagnosed with any stage primary BC
2. Over 18 years of age
3. Receiving or will receive during the study period intravenous chemotherapy, with or without radiotherapy
4. Able to provide informed consent
5. Able to understand and speak English
6. Able to regularly receive and access emails
7. Able and willing to wear bright light glasses
8. Recruitment and consent occurs at the Peter MacCallum Cancer Centre chemotherapy day unit so participants must have an appointment for chemotherapy at the Peter MacCallum Cancer Centre.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
1. Being male
2. Receiving only neoadjuvant chemotherapy
3. Severe psychiatric disorder
4. Severe substance use disorder
5. History of suffering migraines
6. Individuals with very advanced (habitual bedtime before 8pm and rise time before 4am)/delayed sleep timing (habitual bedtime after 3am and rise time after 11am), or have irregular or non-24 sleep/wake patterns are excluded based on the Duke structured sleep interview.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The randomization scheme will be generated and setup in REDCap by a member of the research staff who is (1) not involved in recruitment or delivery of intervention and (2) is not one of the study PIs, CI-Bei. REDCap is a web application and back-end database model designed to support data capture for research studies. REDCap is an open source tool developed by Vanderbilt University to build and manage online forms for data collection (www.project-REDCap.org). REDCap was developed specifically around HIPAA-security guidelines with features such as data encryption. REDCap implements role-based security, which will be used to limit access based on user function to certain forms, reports and fields. To randomize a participant, an authorized research staff member will login to REDCap, enter eligibility and stratification data on the participant and will receive the group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible participants will be randomized into group using a complete randomization scheme generated in advance. Specifically, block sizes of variable size (4, 6, or 8) will be used. Random seeds will be generated to assure allocation concealment and pre-guessing of the allocation sequence at the end of each block. Randomization will be stratified by baseline ISI (<= 7, >= 8) and cancer stage (<= 2, >= 3).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample Size and Power
Based on previous studies of CBT for insomnia (CBT-I) in cancer patients and bright white light (BWL), we expected a moderate to large effect size for the primary outcomes. We are using internet CBT combined with BWL, which each operate on different mechanisms. CBT targets behavioural and cognitive processes and BWL targets circadian processes. Given our combination of CBT + BWL and their different mechanisms of change, we expected larger effects than shown in previous studies utilizing only CBT or BWL. Specifically, we expected a standardized mean difference of d = 0.70, corresponding to a medium-to-large between-group effect at the post-treatment assessment.
Power analyses based on t-tests showed that 35 women in each condition will provide >80% power to detect a standardized mean difference of 0.70 at post treatment. Assuming that 85% of women randomized complete the post-treatment assessment, 40 women need to be randomized to each group to obtain a final post-treatment sample size of 35 per group.
Based on common chemotherapy rates, non-English speaking, and other exclusion criteria, we estimate that approximately 45% of women diagnosed with BC will not meet eligibility criteria. Based on adoption rates in previous CBT-I trials, of eligible women, we estimate that approximately 40% will decline. Therefore, to randomize 80 women, we expect to assess approximately 200 women for eligibility and possible inclusion.
All analyses will be conducted on an intention-to-treat basis. Results for all randomized women will be analysed in the group to which they were assigned regardless of protocol violations. The only exception will be women where consent to use their data in the analysis is withheld or withdrawn. All tests are two-sided, and the nominal level of a will be 5%. All statistical analyses will be unadjusted except where indicated.
Aim 1
Test the efficacy of cognitive behavioural and bright light therapy (CBT+) compared to relaxation audio for improving symptoms of sleep disturbance. Aim 1 will be tested using latent growth models. Latent growth models (LGMs) will be estimated with an intercept and two, linear slopes, representing a piecewise model. Slope 1 will have loadings constrained to 0, 0.5, 1.0, and 1.0 for times t0, t1, t2, and t3, respectively, capturing the linear change from baseline (t0) to post intervention (t2). Slope 2 will have loadings constrained to 0, 0, 0, and 1.0 for times t0, t1, t2, and t3, respectively, allowing a different slope from from post intervention (t2) to follow-up (t3) compared to from baseline to post. The means and variances of the intercept and slope factors will be freely estimated (corresponding to random effects in linear mixed models) and the intercept and slope covariances will be estimated. The residual variance will be constrained to equality across time and residuals assumed uncorrelated, corresponding to an independent, homogenous residual structure. Intercepts of indicators will be constrained to 0 to allow estimation of the latent random intercept mean.
There are two stratification factors: screening ISI (= 7, = 8) and cancer stage (= 2, = 3). These factors will be crossed creating four groups: Early Stage, Low ISI; Advanced Stage, Low ISI; Early Stage, High ISI; and Advanced Stage, High ISI. Dummy codes will be created for each strata, with Early Stage, Low ISI treated as the reference group. These dummy codes will be included as covariates to adjust for their effect on the random intercept, following recommendations that stratification factors be adjusted for in analyses of randomised controlled trials (Kahan & Morris, 2011; Kahan & Morris, 2012).
Treatment effects will be evaluated by creating a dummy code (0 = TAU+, 1 = CBT+). This dummy code will be entered as a predictor of the intercept, Slope 1, and Slope 2. However, treatment factors will be constrained to 0 for the intercept, to implement so-called “constrained longitudinal data analysis” (Coffman, Edelman, Woolson, 2016; Twisk, Bosman, Hoekstra, et al, 2018), which studies show provides a more accurate estimate of treatment effects from randomised controlled trials with repeated measures.
The primary trial results will be the effect of treatment on Slope 1 (i.e., from baseline to post-treatment). This interaction directly tests whether the change in primary outcomes over time is different in the control and intervention arm. Effect sizes of the group difference at each time point also will be calculated.
A similar process will be followed for sleep efficiency, however a continuous time model will be estimated using a mixed effects model in Mplus because up to 42 days of sleep efficiency are collected. Sleep efficiency may not follow a normal distribution. If the assumption of normality is violated, significance tests and confidence intervals will be based on non-parametric bootstrapping.
Aim 2
Test the efficacy of CBT+ versus relaxation audio for psychological outcomes. Aim 2 will be tested identically to Aim 1, but using psychological outcomes in place of the sleep and fatigue outcomes

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11495 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 23519 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 300217 0
University
Name [1] 300217 0
Monash University
Address [1] 300217 0
Monash University
18 Innovation Walk
Clayton, Victoria
3800 Australia
Country [1] 300217 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street
Melbourne Victoria
3000 Australia
Country
Australia
Secondary sponsor category [1] 299626 0
University
Name [1] 299626 0
Monash University
Address [1] 299626 0
18 Innovation Walk
Clayton Victoria
3800 Australia
Country [1] 299626 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301038 0
Peter MacCallum Cancer Centre Human Research Ethics Committee [EC00235]
Ethics committee address [1] 301038 0
305 Grattan Street
Melbourne Victoria
3000 Australia
Ethics committee country [1] 301038 0
Australia
Date submitted for ethics approval [1] 301038 0
27/11/2017
Approval date [1] 301038 0
11/07/2018
Ethics approval number [1] 301038 0
HREC/18/PMCC/188

Summary
Brief summary
This study aims to test the effectiveness of cognitive behaviour therapy in combination with light therapy compared to relaxation audio.

Who is it for?
You may be eligible for this study if you are a woman aged over 18, have a diagnosis of primary breast cancer (any stage) and are receiving (or will receive) chemotherapy.

Study details
Participants will be randomised (by chance) to one of two treatments. One treatment (the Intervention group) is a cognitive behavioural therapy session in addition to use of Light glasses to be worn for 30 minutes each morning. The other group (the Control group) will receive relaxing audio tracks by email. The Control group will receive the information provided to the Intervention group after 3 months. All participants (both groups) will fill out a sleep diary, fill out a questionnaire and wear a watch that measures sleep.

It is hoped that this research will help us understand whether a combined behavioural and bright light intervention can reduce sleep disruption and fatigue during chemotherapy for breast cancer and provide a basis for expanding the treatment to people with other types of cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85670 0
Ms Justine Diggens
Address 85670 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne Victoria
3000
Country 85670 0
Australia
Phone 85670 0
+61 3 8559 5117
Fax 85670 0
Email 85670 0
justine.diggens@monash.edu
Contact person for public queries
Name 85671 0
Dr Joshua F. Wiley
Address 85671 0
Monash University
18 Innovation Walk
Clayton, Victoria
3800 Australia
Country 85671 0
Australia
Phone 85671 0
+61 42 4646 114
Fax 85671 0
Email 85671 0
joshua.wiley@monash.edu
Contact person for scientific queries
Name 85672 0
Dr Joshua F. Wiley
Address 85672 0
Monash University
18 Innovation Walk
Clayton, Victoria
3800 Australia
Country 85672 0
Australia
Phone 85672 0
+61 42 4646 114
Fax 85672 0
Email 85672 0
joshua.wiley@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics approval not currently obtained for sharing of individual data. If ethics approval is obtained, IPD will be de-identified and made available.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Analytic code
How or where can supporting documents be obtained?
Type [1] 4772 0
Study protocol
Citation [1] 4772 0
Link [1] 4772 0
Email [1] 4772 0
Other [1] 4772 0
Publication under review currently, will update registry when available.
Type [2] 4773 0
Statistical analysis plan
Citation [2] 4773 0
Link [2] 4773 0
Email [2] 4773 0
Other [2] 4773 0
Publication under review currently, will update registry when available.
Attachment [2] 4773 0
Type [3] 4774 0
Informed consent form
Citation [3] 4774 0
Link [3] 4774 0
Email [3] 4774 0
Other [3] 4774 0
Will be available after the study through GitHub repository
Type [4] 4775 0
Ethical approval
Citation [4] 4775 0
Link [4] 4775 0
Email [4] 4775 0
Other [4] 4775 0
Will be available after the study through GitHub repository
Attachment [4] 4775 0
Type [5] 4776 0
Analytic code
Citation [5] 4776 0
Link [5] 4776 0
Email [5] 4776 0
Other [5] 4776 0
Will be available after the study through GitHub repository
Attachment [5] 4776 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary