Calm for Hematological Cancer Sleep Disturbance
Study Details
Study Description
Brief Summary
In a double blind RCT, the investigators will recruit participants to an 8-week "app-based wellness" intervention: the active daily meditation intervention (Calm) or the placebo health education podcast control group (POD), followed by a 12-week follow-up period. The 288 CHC patients (representative of age, race/ethnicity, and gender), will be on stable CHC pharmacologic therapy (if any), self-identify as sleep disturbed (>5 on Pittsburgh Sleep Quality Index), do not have a sleep disorder diagnosis, do not take sleep medication/supplements >3 times per week, and have not practiced regular meditation in the past six months.
Aim 1: Test the efficacy of daily meditation (10 minutes/day) delivered via Calm compared to POD on the primary outcome of self reported sleep disturbance (Insomnia Severity Index (primary) and PROMIS Sleep Disturbance (secondary)) and secondary sleep outcomes including sleep impairment (PROMIS Sleep Impairment Scale) and sleep efficiency measured via sleep diaries and actigraphy.
Hypothesis: Participants who are administered Calm will experience reduced sleep disturbance, and improvements in secondary sleep outcomes compared to POD at eight weeks.
Aim 2: Test the efficacy of daily meditation (10 minutes/day) delivered via Calm compared to POD on inflammatory markers (i.e., TNF-a, IL-6, IL-8, CRP), fatigue, and emotional distress (i.e., anxiety, depressive symptoms measured with PROMIS®).
Hypothesis: Participants who are administered Calm will have greater reductions in fatigue, emotional distress and inflammatory markers compared to POD at eight weeks.
Aim 3: Explore the sustained effects (i.e., 20 weeks from baseline) of Calm in CHC patients.
Hypothesis: (a) Participants in Calm will have greater reductions in sleep disturbance, fatigue, emotional distress and inflammatory markers compared to POD at 20 weeks; (b) Total meditation time and sustained meditation usage overtime, but not time of day or use of non-meditative content (e.g., Sleep Stories), will be related to improved outcomes at 20 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Hematological cancers account for 11% of all cancer diagnoses in the US. Chronic hematological cancer (CHC) patients are characterized by long term and high symptom burden. Up to 65% of CHC patients report chronic sleep disturbances (e.g., difficulty falling asleep, difficulty staying asleep, non restorative sleep, insomnia) that are highly correlated with poorer cognitive and physical functioning, increases in fatigue and emotional distress, and heightened levels of specific inflammatory markers (TNF-a, IL-6, IL-8, CRP) that negatively impact quality of life. Sleep interventions have been tested in solid tumor patients, but no research has examined sleep interventions specifically for CHC patients. Medications are commonly prescribed but often come with side effects and risk for long-term dependence. Cognitive behavioral therapy for insomnia (CBT-I) is the most studied and first line of therapy for treating sleep disturbances in cancer patients, but CBT-I is time-consuming, resource-intensive, and not easily accessible for all cancer patients. There is a need for long-term, accessible, non-pharmacologic interventions targeting sleep in CHC patients.
RCTs have shown meditation and mindfulness-based interventions lead to improvements in sleep disturbance among breast cancer patients, but this research has not been extended to CHCs. Meditation has potential as a non-pharmacologic strategy to reduce sleep disturbance in CHC patients without the time and expertise limitations of CBT-I and side effect risks from medication. In person meditation, however, is still inaccessible long term due to potential fatigue, pain, transportation, and scheduling difficulties.
Smartphone apps have attracted considerable interest from cancer patients as an easily accessible and empowering way to self-manage health. Existing research using apps has focused on short term psychological measures (e.g., distress, cancer-related distress, anxiety, etc.) or cancer-specific biological changes as outcomes and not sleep disturbance, in solid tumor survivors with minimal residual disease (e.g., breast cancer post-treatment), or those with short survival (e.g., metastatic solid tumor patients). The unique, long-lasting disease course of CHC patients and high chronic symptom burden warrants distinct interventions from resolved solid tumor patients. CHC patients with sleep disturbance have no options for easily accessible and evidence-based treatments for sleep disturbances. The investigators propose the first RCT to determine the effects of a consumer-based mobile meditation app on sleep disturbance in CHC patients.
The investigators have a unique academic-industry partnership with the consumer-based meditation mobile app, Calm. Calm has the broad reach and popularity to deliver meditation to remote CHC patients. Our formative work shows Calm to be a feasible and preferred method for delivering meditation to CHC patients (including older adults) compared to another meditation app. Notably, patients reported significant post-intervention reductions in sleep disturbance in only four weeks. Our health education podcast, with no significant effects on sleep, matched for attention, time, and dose is shown to be an acceptable and appropriate active control to compare to Calm.
Study Timeline:
This study is expected to last 5 years. The investigators will begin recruiting in June 2022 and expect, based on enrollment rates of prior feasibility and pilot work, an average monthly enrollment rate of ~10 participants each month. The investigators will recruit 276 CHC patients and enroll them into the intervention between months 7-48 (~42 months; providing a small buffer of time to finish recruitment and enrollment if needed). The investigators expect to enroll the last study participant in month 48, meaning intervention delivery will be completed by month 50 (i.e., 8-weeks after last participant is enrolled) and follow-up will be completed by month 53 (i.e., 20-weeks after last participant is enrolled). The investigators are confident the investigators can enroll participants in less than 42 months because in our two prior studies recruiting hematological cancer patients for online yoga, 244 and 260 completed eligibility within a month (2015 and 2016, respectively). In our feasibility study for meditation apps the investigators recruited 289 for eligibility in two months and enrolled 128 CHC patients in four months. Monthly, the investigators will conduct team meetings and check on data quality and conduct data safety monitoring board reviews once each year. Upon the completion of data collection in year 5 (i.e., month 53), the investigators will perform data analysis and write manuscripts for publication.
Procedures:
Calm is a subscription-based meditation app that provides guided meditations, sleep stories, soundscapes and calming music. Calm offers 7 Days of Calm for those new to meditation, the daily Calm, a meditation posted daily and a library of unique 10-12 minute meditations with topics related to acceptance, anxiety, self-compassion, and physical pain (to name a few). Calm has over 50 million users and over 800,000 5-star reviews. It has been named Google Play Editor's Choice 2018 award winner and Apple's App of the Year in 2017. If Calm has a significant clinical impact on sleep disturbance in CHC patients, the investigators will have an inexpensive, easily accessible, non-pharmacologic intervention that can readily be prescribed by cancer care providers for sleep disturbance for CHC. Our rigorous RCT will fill a knowledge and rigor gap regarding the delivery of smartphone-based meditation as an intervention for sleep and provide new data on sustained effects.
Study Design - The study design is a two-group, double-blind RCT. Assessments will occur at baseline, post-intervention (eight weeks from baseline), and follow-up (20 weeks from baseline). Participants will be recruited to an "app-based wellness" intervention. Male and female CHC patients will be blindly and randomly assigned to one of two groups (1) at least 10 minutes per day of Calm meditation (Calm group) or (2) at least 10 minutes per day of educational podcasts (attention, time, and dose matched (POD group), both delivered via a smartphone app. Participants will be randomly assigned to a given group after baseline assessments and obtained consent. Specifically, participants will be blocked or stratified by gender and then randomly allocated (with a 1:1 allocation) within the male-female strata to treatments using a pseudorandom number algorithm provided by the study statistician. Research personnel who assign participants to a group will not be the same as those who enroll participants or download and clean data. Group allocation status will be restricted so that statisticians and PIs will also remain blind to treatment assignment.
Eligibility - Eligibility includes: (a) Stable medical therapy for CHC (i.e., no change over the previous two months or plans to change pharmacologic therapy (if any) during the trial period of 20 weeks). This criterion allows treatment effects to remain stable during the time of the intervention. Weekly tracking will be conducted in the event of unanticipated changes; (b) Sleep Disturbance: Self-identification as sleep disturbed using the Pittsburgh Sleep Quality Index score (>5). The investigators will exclude (a) Pre-existing meditation practice and/or meditative movement practice (e.g., yoga, tai chi, qi gong that includes substantial meditation) for more than 60 minutes per week in the past six months; (b) Patients diagnosed with any sleep disorder (e.g., sleep apnea, restless leg syndrome) except for insomnia. The investigators will assess sleep disorder diagnosis history and exclude high risk for sleep apnea using the Berlin Questionnaire (≥2 positive categories), (c)Those who take medications/supplements for sleep ≥3 times per week. Infrequent users will be asked to refrain from use during the trial; (d) Patients with uncontrolled, other medical or psychiatric conditions.
Sample Size and Power - The investigators will enroll and randomize 276 participants (n=138/study arm), which, assuming up to 20% attrition by Week 8 and up to 30% attrition by Week 20 will afford power=.80 to detect standardized between-arm differences of d=0.45 (Week 8; Aims 1 and 2) and d=0.48 (Week 20, Aim 3) in both primary and secondary outcomes. Full-sample and within-arm (i.e., Calm arm only) examination of dose effects at Week 20 (Aim 3) will have power=.80 to detect small (r2 ≥ .039) and moderate (r2 ≥ .076) linear dose-response effects, respectively.
Recruitment - The investigators will recruit male and female CHC patients with representative samples of ethnic and racial minorities nationally. Participants will be told prior to randomization that they will be randomized to an "app-based wellness" study for hematological cancer patients and thus will be blinded to the intended arm assignment. Given the prevalence of sleep disturbance and our success in recruitment of other rare hematologic malignancy patients, the investigators are confident the investigators can recruit 10 participants per month.
The investigators will recruit CHC patients nationally using successful recruitment strategies used in our prior work. These strategies include:
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postings on both hematological-specific and general cancer social media pages (i.e., Facebook, Instagram, and Twitter),
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postings on hematological-specific and general cancer email listservs,
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contact with organizational partners (e.g., Leukemia & Lymphoma Society, MPN Research Foundation, Patient Empowerment Network) to post recruitment information on their website and social media/support group sites, and
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direct contact with hematological cancer patients who previously expressed interest in our future studies.
Enrollment - In compliance with COVID-19, all study procedures are remote. Interested patients will complete an online eligibility questionnaire via Qualtrics. Ineligible participants will be sent an email notifying them of their ineligibility status. Eligible participants will be sent an email notifying them of their eligibility, asked to review a video-based overview of the study (including the informed consent), and an invitation to electronically sign the informed consent via Qualtrics. Once the consent is signed, participants will be asked to complete the baseline questionnaire via Qualtrics, randomly assigned to their group (Calm or POD), and emailed blood draw and actigraph materials.
After randomization, all participants will be offered an app download coaching/tutorial/practice call with a study team member to review the Calm or POD app, depending on their assigned group. For the current study, during the app download app familiarization call with participants a study team member will review 1) the general layout and basic functionalities of the app (e.g., look, feel, types of content found on app, etc.), 2) where to find content and how the content is organized (i.e., meditations or podcasts), 3) how to view participation tracking stats on the app, 4) how to set reminders to meditate/view podcasts, and 5) how to share participation stats on social media. Following the call, participants will receive an email containing a phone number to reach a research team member during business hours for continued support using the app, blood draw instructions, and a notification that they will be receiving a package containing an Actiwatch (actigraphy) device.
Blood draw instructions will advise on making an appointment with the nearest Quest Diagnostics Patient Service Center (2,200 centers located across the U.S.) Authorized accounts will be set up through Quest Diagnostics. Participants will receive a Lab Order Confirmation form to present to staff with a valid ID, name and date of birth The investigators will ask participants to have their blood drawn in the morning, within two weeks of notifying research personnel that they received their package, and to repeat their blood draw at post-intervention (eight weeks), and follow up (20 weeks). The research team will access the blood draw data using Care360, a web-based patient platform that provides a secure and confidential location to store and view test results (i.e., information is only accessible with an authorized account number).
The package containing the Actiwatch will arrive prior to the participant beginning their baseline assessments. Participants will wear the Actiwatch daily throughout the duration of the eight-week intervention period, mail it back to research personnel after week eight (the Actiwatch has a maximum battery life of 68 days), and receive an Actiwatch to wear again for a 7-day period during the follow-up period (i.e., week 20). Throughout the study, participants will also be asked to keep a weekly sleep diary online.
Intervention - Calm meditation focuses on mindfulness components, breathing techniques and body scans, all of which are consistent with core mindfulness practices, including Mindfulness-based Stress Reduction (nonjudgmental moment-to moment awareness) and Vipassana (objective observation of physical sensation in the body). Calm does not provide its users with a specific prescription nor durations or frequencies in which to engage with the app, instead the frequency, dose, and timing of engagement, as well as its content and use of features is entirely self-selected by the user. Participants assigned to the Calm group will be asked to complete a minimum of 10 minutes per day of meditation, at any time of day they choose for eight weeks. During weeks 1-4 participants in the Calm group will be asked to complete the introductory 30-day program "How to Meditate" (i.e., 30 days of a 10-minute daily meditation with education about what mindfulness is, how to practice it and achieve it with meditation, which seated or laying positions to use for meditation, and how to monitor their breathing). "How to Meditate" educates participants about how mindfulness meditation affects daily life, such as reducing stress and quieting the mind. Weeks 5-8, participants will be asked to complete one daily meditation that may include the "Daily Calm," a different 10-minute mindfulness meditation each day, or a meditation from a various series of meditations (e.g., loving-kindness, seven days of managing stress). Participants will have complete autonomy to choose the meditation. After the participant has completed their daily meditation, participants will also be able to use the app content more broadly (i.e., non meditative content including Sleep Stories) based on their preference.
Participation (meditations completed, time of day, length of time, non-meditative content used) will be tracked using the Calm app throughout the study and addressed in sensitivity analyses.
Control - Similar to the Calm group, participants in the POD group will listen to a minimum of 10 minutes per day of a health education podcast delivered via a mobile app for eight weeks. Content was carefully chosen to exclude any recommendations for sleep, meditation, or for mindfulness-like principles or practice. A library of podcasts is available on the app. Participants are able to select the podcast based on title, time or both in an effort to mirror the delivery of the meditations in the Calm group. Similar to the Calm group, the POD group will be encouraged to use the other components of the podcast app (which the investigators will review in detail during the intake appointments). Participation (podcasts completed, time of day, length of time, components used) will also be tracked on the app throughout the study period.
Follow-up - After the intervention (eight weeks), the research team will notify participants that they will no longer receive email/text reminders but will still have free access to their app for three months. The investigators will continue to track participation of Calm/POD until 20 weeks from baseline.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Calm Meditation Participants assigned to the Calm group will be asked to complete a minimum of 10 minutes per day of meditation, at any time of day they choose for eight weeks. During weeks 1-4 participants in the Calm group will be asked to complete the introductory 30-day program "How to Meditate". Weeks 5-8, participants will be asked to complete one daily meditation that may include the "Daily Calm," a different 10-minute mindfulness meditation each day, or a meditation from a various series of meditations (e.g., loving-kindness, seven days of managing stress). Participants will have complete autonomy to choose the meditation. After the participant has completed their daily meditation, participants will also be able to use the app content more broadly based on their preference. |
Behavioral: Calm Meditation
This is the active intervention group.
Other Names:
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| Active Comparator: Health Education Podcast Similar to the Calm group, participants in the POD group will listen to a minimum of 10 minutes per day of a health education podcast delivered via a mobile app for eight weeks. Content was carefully chosen to exclude any recommendations for sleep, meditation, or for mindfulness-like principles or practice. A library of podcasts is available on the app. Participants are able to select the podcast based on title, time or both in an effort to mirror the delivery of the meditations in the Calm group. Similar to the Calm group, the POD group will be encouraged to use the other components of the podcast app (which we will review in detail during the intake appointments). Participation (podcasts completed, time of day, length of time, components used) will also be tracked on the app throughout the study period. |
Behavioral: Health Education Podcast
This is the active comparator/control group.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Sleep Disturbance (subjective) [Changes in sleep disturbance will be measured at baseline, week 8, and week 20. Total scores range from 0 to 28 with scores 8 to 14, and ≥15 indicating subclinical and moderate-to-severe insomnia symptom severity, respectively.]
Sleep disturbance will be measured with the Insomnia Severity Index (ISI). Total scores range from 0 to 28 with scores 8 to 14, and ≥15 indicating subclinical and moderate-to-severe insomnia symptom severity, respectively.
- Sleep Disturbance (subjective) [Changes in sleep disturbance will be measured at baseline, week 8, and week 20. This form consists of 8 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.]
Sleep disturbance will be measured with the Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8b. This form consists of 8 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.
- Sleep Disturbance (subjective) [Changes in sleep disturbance will be measured at baseline, week 8, and week 20. This form consists of 8 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.]
Sleep disturbance will be measured with the Patient Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment. This form consists of 8 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.
- Sleep disturbance (subjective) [Changes in sleep disturbance will be measured weekly throughout the 8-week intervention period and once again during the week 20 follow-up period.]
Sleep disturbance will be measured with an investigator-developed weekly sleep diary
- Sleep disturbance (objective) [Changes in sleep disturbance will be measured weekly throughout the 8-week intervention period and once again during the week 20 follow-up period.]
Sleep disturbance will be measured with wrist actigraphy
Secondary Outcome Measures
- Inflammation [Changes in inflammation will be measured at baseline, week 8, and week 20.]
Inflammation will be measured with blood serum cytokines (C-reactive protein, TNF-a, IL-6, IL-8)
- Fatigue (subjective) [Changes in fatigue will be measured at baseline, week 8, and week 20.]
Fatigue will be measured with the Patient Reported Outcomes Measurement Information System (PROMIS) Adult Cancer Fatigue Short Form 7a. This form consists of 7 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.
- Anxiety (subjective) [Changes in anxiety will be measured at baseline, week 8, and week 20.]
Fatigue will be measured with the Patient Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Anxiety Short Form 7a. This form consists of 7 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.
- Depression (subjective) [Changes in fatigue will be measured at baseline, week 8, and week 20.]
Fatigue will be measured with the Patient Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Depression Short Form 8a. This form consists of 8 items in a 1-5 Likert scale. The measure generates a total summed score, which is then converted to a standardized t-score.
Other Outcome Measures
- Meditation Participation [Changes in meditation participation will be measured on a weekly basis throughout the 8-week intervention period.]
Participation with meditation using the Calm app will be measured by the Calm app tracking
- Podcast Participation [Changes in podcast participation will be measured on a weekly basis throughout the 8-week intervention period.]
Participation with podcast listening/viewing using the podcast app will be measured by the podcast app tracking
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of chronic hematological cancer on stable maintenance management* by treating physician (i.e., a. On stable medical therapy or observation (i.e., no changes in disease targeted medications (or their dose) for the past two months
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Not currently participating in a therapeutic pharmacologic clinical trial
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Has not received/planning to receive an allogenic stem cell transplantation)
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Score of >5 on Pittsburgh Sleep Quality Index (PSQI)
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Own a mobile smartphone (iPhone with iOS 9.0 or later or an Android 4.1 or later)
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Willing to download a mobile app
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Able to read/understand English
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≥18 years of age
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Willing to be randomized
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Willing to drive to Quest Diagnostics Patient Service Center 3x during the study in the morning
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No change in sleep medication use (if any) over the past six weeks
Exclusion Criteria:
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Self-report a meditation practice or meditative movement practice (i.e., yoga, tai chi, qi gong) of ≥60 min/week in past 6 months
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Report the use of any consumer-based meditation app
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Reside outside of the United States of America
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Any planned change in pharmacologic therapy (i.e., new drug) or allogenic stem cell transplantation during study timeframe (i.e., 20 weeks)
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Diagnosed with a sleep disorder except insomnia (≥2 positive categories on Berlin Questionnaire)
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Taking sleep medications/supplements >3 times per week
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Any other diagnosed and uncontrolled medical or psychiatric condition
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<18 years of age
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Unable to consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Calm, Inc. | San Francisco | California | United States | 94105 |
Sponsors and Collaborators
- Calm.com, Inc.
- The University of Texas Health Science Center at San Antonio
- Quest Diagnostics-Nichols Insitute
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Calm2021-104