Childhood Cancer, Insomnia, Late Effect, Neurocognitive Impairment, Sleep, Survivorship
Conditions
Brief summary
There is evidence that survivors of childhood cancer have a high prevalence of poor sleep, including symptoms of insomnia. Insomnia is highly comorbid and has been associated with impaired cognitive performance, a range of psychiatric disorders, cardiovascular disease, and reduced quality of life. However, we still lack knowledge about the direct impact of available internet-based insomnia treatment programs for survivors of childhood cancer experiencing insomnia, in addition to how improving insomnia symptoms impacts neurocognitive function and late health morbidities in this population. Therefore, in this study, we will utilize the resources available in the Childhood Cancer Survivor Study (CCSS) to use an accepted, established, efficacious internet-delivered CBTi insomnia treatment program and evaluate the efficacy of this program in adult survivors of childhood cancer. Positive results from this study and our use of an internet-based intervention are likely generalizable and be scalable to the large and geographically diverse population of childhood cancer survivors with chronic health conditions. Primary Objective To examine the efficacy of an eHealth intervention for improving symptoms of insomnia among adult survivors of childhood cancer. Secondary Objectives To examine the impact of an eHealth intervention for insomnia on the clinical severity of insomnia symptoms in adult survivors of childhood cancer. To determine whether treatment of insomnia symptoms will improve neurocognitive function in adult survivors of childhood cancer with both insomnia and neurocognitive impairment. To explore the mediating effects of improved neurocognitive function, emotional distress, and cardiovascular health on the association between insomnia symptoms and quality of life.
Detailed description
Participants with clinically significant insomnia and neurocognitive impairment are eligible for the current study. Participants will complete a 9-week internet-based insomnia treatment program (SHUTi) or receive sleep education, depending on randomized group assignment. Participants will complete home-based assessments at 3 time points (baseline, post-intervention, 6 months). These assessments will include online questionnaires measuring insomnia symptoms, neurocognitive problems, fatigue, daytime sleepiness, and health related quality of life. In addition, at each time point participants will be asked to wear an activity monitor for one week to measure physical activity and sleep patterns. Each assessment time point will also include assessment of cardiovascular biomarkers (dried blood spot cards) and neurocognitive function (CNS Vital Signs).
Interventions
DEVICESleep Healthy Using the Internet (SHUTi) Intervention Group
SHUTi is a fully automated, interactive and tailored web-based program that incorporates the primary tenets of face-to-face CBT-I, including sleep restriction, stimulus control, cognitive restructuring, sleep hygiene, and relapse prevention. Intervention content is presented in six Cores, metered out over time.
DEVICEOnline Patient Education (PE) Control Group
The online PE program provides static information about: insomnia symptoms; the impact, prevalence, and causes of insomnia; when to see a doctor; and basic lifestyle, environmental, and behavioral strategies to improve sleep.
Sponsors
National Cancer Institute (NCI)
St. Jude Children's Research Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Enrollment in CCSS * Between the ages of 18 and 65 years old * Meeting at least one of the following three insomnia criteria: * Clinically significant insomnia (i.e. score ≥8 on the Insomnia Severity Index) * Delayed sleep onset latency (SOL) (i.e. cannot get to sleep within 30 minutes, three or more times a week) * Excessive wake after sleep onset (WASO) (i.e. nighttime awakenings lasting a total of at least 30 minutes, three or more times per week) * Neurocognitive impairment (i.e. score \>84th %ile of sibling normative data in at least one domain on the CCSS-NCQ) * Regular access to the internet (at least 2-3 days per week) * Ability to read and speak English * Access to a desktop computer or a laptop * Access to a smart phone (android or iPhone), tablet or iPad with Bluetooth Low Energy BLE 4.2 or higher
Exclusion criteria
* History of a brain tumor * An irregular schedule that would prevent adoption of intervention strategies (i.e. work schedule resulting in usual bedtime earlier than 8 PM or later than 2 AM or arising time earlier than 4 AM or later than 10 AM) * Currently pregnant or breast feeding * Behavioral treatment for insomnia in the past 12 months * Diagnosis of schizophrenia or a psychotic disorder * Alcohol or drug abuse in past year * Other concurrent sleep disorders, including narcolepsy, obstructive/central sleep apnea, or restless leg syndrome * Current treatment or intervention for cognitive impairment (i.e. stimulant medication, transcranial direct current stimulation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insomnia Severity Index (ISI) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Baseline and Post-Intervention (approximately 10 weeks after Baseline)] | This is a 7-item, Likert scale, self-report questionnaire assessing perception of sleep and consequences of insomnia. The scores range from 0 to 28 with higher values indicating increasing symptom burden. Changes in scores on a scale from baseline to post-intervention are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Baseline and Post-Intervention (approximately 10 weeks after Baseline) | The CCSS-NCQ was developed specifically to address neurocognitive concerns of adult survivors of childhood cancer and includes assessment of problems with memory, task efficiency, organization, and emotional regulation. The domains of memory, task efficiency, and emotional regulation are used in this study. Z-scores are calculated using sibling normative data (Mean=1, SD=0) with higher scores indicating worse problems. Changes in z-scores from baseline to post-intervention are reported. |
| Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Baseline and Post-Intervention (approximately 10 weeks after Baseline)] | This is a computerized assessment that measures 3 domains of cognitive function; Executive Function, Processing Speed and Memory. Age, sex, and race specific Standard Scores (M=100, SD=15) are calculated. Higher scores indicate better functioning. Changes in standard scores from baseline to post-intervention are reported. |
| Change in Patient Health Questionnaire (PHQ-8) Scores From Baseline to 6-Month Follow-Up (Approximately 6 Months After Baseline) | Baseline and 6-Month Follow up (approximately 6 months after Baseline) | This questionnaire measures symptoms of depression. Scores range from 0 to 24 with higher scores indicating more severe symptoms. Changes in scores on a scale from baseline to 6-month follow-up are reported. |
| Change in Generalized Anxiety Disorder-7 (GAD-7) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | Baseline and 6-Month Follow up (approximately 6 months after Baseline) | This questionnaire measures symptoms of anxiety with scores ranging from 0 to 21. Higher scores indicate greater symptoms of anxiety. Changes in scores on a scale from baseline to 6-month follow-up are reported. |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Questionnaire (HRQoL) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | Baseline and 6-Month Follow up (approximately 6 months after Baseline) | This questionnaire measures general health-related quality of life in the domains of physical and mental health. T-scores are calculated (M=50, SD=10) with higher scores indicated better quality of life. The PROMIS scoring tables were used for scoring. Changes in T-scores from baseline to 6-month follow-up are reported. |
Countries
United States
Participant flow
Recruitment details
1554 participants were screened and enrolled between December 2020 and February 2024. Of these, 989 were ineligible, 9 withdrew and 15 were lost to follow-up prior to randomization. 541 participants were randomized.
Pre-assignment details
The remaining 541 participants were randomized to complete the SHUTi intervention program or to review the online patient education materials for 9 weeks. Participants were randomized using a permuted-block method with random block sizes, stratified on sex (male/female), age (\<40/\>40), and cranial radiation therapy (yes/no).
Participants by arm
| Arm | Count |
|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group Participants access and complete the SHUTi program for 9 weeks.
Sleep Healthy Using the Internet (SHUTi) Intervention Group: SHUTi is a fully automated, interactive and tailored web-based program that incorporates the primary tenets of face-to-face CBT-I, including sleep restriction, stimulus control, cognitive restructuring, sleep hygiene, and relapse prevention. Intervention content is presented in six Cores, metered out over time. | 273 |
| Online Patient Education (PE) Control Group Participants access and review online patient education for 9 weeks.
Online Patient Education (PE) Control Group: The online PE program provides static information about: insomnia symptoms; the impact, prevalence, and causes of insomnia; when to see a doctor; and basic lifestyle, environmental, and behavioral strategies to improve sleep. | 268 |
| Total | 541 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 57 | 59 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Withdrawal by Subject | 46 | 24 |
Baseline characteristics
| Characteristic | Total | Sleep Healthy Using the Internet (SHUTi) Intervention Group | Online Patient Education (PE) Control Group |
|---|---|---|---|
| Age, Continuous | 44.7 Years STANDARD_DEVIATION 8.7 | 44.6 Years STANDARD_DEVIATION 8.7 | 44.8 Years STANDARD_DEVIATION 8.7 |
| Race/Ethnicity, Customized Black, non-Hispanic | 17 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic | 37 Participants | 19 Participants | 18 Participants |
| Race/Ethnicity, Customized Other races, non-Hispanic | 26 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White, non-Hispanic | 458 Participants | 232 Participants | 226 Participants |
| Region of Enrollment United States | 541 participants | 273 participants | 268 participants |
| Sex: Female, Male Female | 395 Participants | 197 Participants | 198 Participants |
| Sex: Female, Male Male | 146 Participants | 76 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 273 | 0 / 268 |
| other Total, other adverse events | 0 / 273 | 0 / 268 |
| serious Total, serious adverse events | 0 / 273 | 0 / 268 |
Outcome results
Primary
Change in Insomnia Severity Index (ISI) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline)
This is a 7-item, Likert scale, self-report questionnaire assessing perception of sleep and consequences of insomnia. The scores range from 0 to 28 with higher values indicating increasing symptom burden. Changes in scores on a scale from baseline to post-intervention are reported.
Time frame: Baseline and Post-Intervention (approximately 10 weeks after Baseline)]
Population: Analysis based on intent to treat. Include participants who were randomized and completed both the baseline and 10-week post-intervention assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Insomnia Severity Index (ISI) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | -6.30 Score on a scale | Standard Deviation 5.04 |
| Online Patient Education (PE) Control Group | Change in Insomnia Severity Index (ISI) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | -3.91 Score on a scale | Standard Deviation 4.62 |
Secondary
Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline)
The CCSS-NCQ was developed specifically to address neurocognitive concerns of adult survivors of childhood cancer and includes assessment of problems with memory, task efficiency, organization, and emotional regulation. The domains of memory, task efficiency, and emotional regulation are used in this study. Z-scores are calculated using sibling normative data (Mean=1, SD=0) with higher scores indicating worse problems. Changes in z-scores from baseline to post-intervention are reported.
Time frame: Baseline and Post-Intervention (approximately 10 weeks after Baseline)
Population: Analysis based on intent to treat. Include participants who were randomized and completed both the baseline and 10-week post-intervention assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Task efficiency | -0.70 Z-score | Standard Deviation 1 |
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Memory | -0.65 Z-score | Standard Deviation 1.01 |
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Emotional regulation | -0.66 Z-score | Standard Deviation 0.9 |
| Online Patient Education (PE) Control Group | Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Task efficiency | -0.41 Z-score | Standard Deviation 0.92 |
| Online Patient Education (PE) Control Group | Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Memory | -0.36 Z-score | Standard Deviation 0.87 |
| Online Patient Education (PE) Control Group | Change in Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Emotional regulation | -0.43 Z-score | Standard Deviation 0.81 |
Secondary
Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline)
This is a computerized assessment that measures 3 domains of cognitive function; Executive Function, Processing Speed and Memory. Age, sex, and race specific Standard Scores (M=100, SD=15) are calculated. Higher scores indicate better functioning. Changes in standard scores from baseline to post-intervention are reported.
Time frame: Baseline and Post-Intervention (approximately 10 weeks after Baseline)]
Population: Analysis based on intent to treat. Include participants who randomized and completed both the baseline and 10-week post-intervention assessments. Participants with missing or invalid CNS Vital Signs assessment in each domain (Executive function, n = 54; Memory, n = 48; Processing Speed, n=36) were removed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Executive function | 1.9 Standard score | Standard Deviation 13 |
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Memory | 2.6 Standard score | Standard Deviation 15.7 |
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Processing speed | 3.9 Standard score | Standard Deviation 12.7 |
| Online Patient Education (PE) Control Group | Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Executive function | 3.5 Standard score | Standard Deviation 11.8 |
| Online Patient Education (PE) Control Group | Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Memory | 0.1 Standard score | Standard Deviation 17.2 |
| Online Patient Education (PE) Control Group | Change in CNS Vitals Signs Scores From Baseline to Post-Intervention (Approximately 10 Weeks After Baseline) | Processing speed | 3.3 Standard score | Standard Deviation 11.9 |
Secondary
Change in Generalized Anxiety Disorder-7 (GAD-7) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline)
This questionnaire measures symptoms of anxiety with scores ranging from 0 to 21. Higher scores indicate greater symptoms of anxiety. Changes in scores on a scale from baseline to 6-month follow-up are reported.
Time frame: Baseline and 6-Month Follow up (approximately 6 months after Baseline)
Population: Analysis based on intent to treat. Include participants who were randomized and completed both the baseline and 6-month follow-up assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Generalized Anxiety Disorder-7 (GAD-7) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | -2.3 Score on a scale | Standard Deviation 4 |
| Online Patient Education (PE) Control Group | Change in Generalized Anxiety Disorder-7 (GAD-7) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | -1.4 Score on a scale | Standard Deviation 4.6 |
Secondary
Change in Patient Health Questionnaire (PHQ-8) Scores From Baseline to 6-Month Follow-Up (Approximately 6 Months After Baseline)
This questionnaire measures symptoms of depression. Scores range from 0 to 24 with higher scores indicating more severe symptoms. Changes in scores on a scale from baseline to 6-month follow-up are reported.
Time frame: Baseline and 6-Month Follow up (approximately 6 months after Baseline)
Population: Analysis based on intent to treat. Include participants who randomized and completed both the baseline and 6-month follow-up assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Patient Health Questionnaire (PHQ-8) Scores From Baseline to 6-Month Follow-Up (Approximately 6 Months After Baseline) | -2.7 Score on a scale | Standard Deviation 4.1 |
| Online Patient Education (PE) Control Group | Change in Patient Health Questionnaire (PHQ-8) Scores From Baseline to 6-Month Follow-Up (Approximately 6 Months After Baseline) | -1.3 Score on a scale | Standard Deviation 4.3 |
Secondary
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Questionnaire (HRQoL) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline)
This questionnaire measures general health-related quality of life in the domains of physical and mental health. T-scores are calculated (M=50, SD=10) with higher scores indicated better quality of life. The PROMIS scoring tables were used for scoring. Changes in T-scores from baseline to 6-month follow-up are reported.
Time frame: Baseline and 6-Month Follow up (approximately 6 months after Baseline)
Population: Analysis based on intent to treat. Include participants who were randomized and completed both the baseline and 6-month follow-up assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Questionnaire (HRQoL) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | Physical health | 2.5 T-score | Standard Deviation 5.7 |
| Sleep Healthy Using the Internet (SHUTi) Intervention Group | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Questionnaire (HRQoL) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | Mental health | 2.6 T-score | Standard Deviation 7.1 |
| Online Patient Education (PE) Control Group | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Questionnaire (HRQoL) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | Physical health | 1.0 T-score | Standard Deviation 5.3 |
| Online Patient Education (PE) Control Group | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Questionnaire (HRQoL) Scores From Baseline to 6-Month Follow-up (Approximately 6 Months After Baseline) | Mental health | 1.0 T-score | Standard Deviation 6.3 |