Prescription Digital Therapeutic for the Treatment of Insomnia (SLEEP-I)

Randomized Controlled Trial Examining Real-World Effectiveness of a Prescription Digital Therapeutic for the Treatment of Insomnia

Mayo Clinic, National Evaluation System for health Technology Coordinating Center (NESTcc), Pear Therapeutics, Inc.

This will be a prospective multi-center controlled trial of 100 patients conducted to assess the real-world effectiveness of a mobile-delivered, prescription digital therapeutic (PDT) device delivering Cognitive Behavioral Therapy for Insomnia using a novel patient-centered data-sharing platform with linkage to Fitbit for 61 weeks

This is a multi-center, randomized, controlled trial to assess the real-world effectiveness of a mobile-delivered, prescription digital therapeutic (PDT) device delivering Cognitive Behavioral Therapy for Insomnia (i.e., Somryst, herein called PEAR-003b) using a novel patient-centered data sharing platform (called Hugo), with linkage to Fitbit (Inspire 2), among 100 patients with chronic insomnia. Half of the patients with insomnia will receive the PEAR-003b digital therapeutic with linkage to the Hugo platform and Fitbit (Inspire 2) and half of the patients with insomnia will not receive the PDT but will receive a Fitbit and be enrolled in the Hugo platform. The treatment duration will be 9 weeks with a 21-, 35-, and 61-week follow-up. All patients will be evaluated at baseline, as well as prompted to complete additional assessments at weeks 9, 21, 35, and 61. The PEAR-003b intervention will deliver CBT-I via mobile devices as 6 treatment core modules over 9 weeks. Additionally, the Hugo platform will be used to collect patient-generated engagement data, healthcare utilization outcomes, and patient activity/clinical outcomes. These real-world data points and trends collected as part of this pilot investigation will help inform a future larger healthcare effectiveness and outcomes research study.

Participants will receive the PEAR-003b digital therapeutic, a Fitbit, and materials on sleep hygiene and healthy sleep tips. Using the Hugo platform, patient-generated engagement data, healthcare utilization, and patient activity/clinical outcomes for patients with insomnia will also be collected.

Participants will receive a Fitbit, and materials on sleep hygiene and healthy sleep tips. Using the Hugo platform, patient-generated engagement data, healthcare utilization, and patient activity/clinical outcomes for patients with insomnia will also be collected.

The PEAR-003b digital therapeutic delivers CBT-I via mobile devices as 6 treatment core modules over 9 weeks.

Insomnia will be measured by the Insomnia Severity Index (ISI) score. Participants rate the severity of sleep problems (e.g. problems with sleep onset, sleep maintenance, and early morning awakening), interference with daytime functioning, how noticeable the impairment is to others, distress or concern caused by the sleep problem(s), as well as satisfaction with the current sleep pattern on a 5-point Likert scale. The ISI's total score ranges from 0 (not clinically significant) to 28 (clinically significant)

Insomnia will be measured by the Insomnia Severity Index (ISI) score. Participants rate the severity of sleep problems (e.g. problems with sleep onset, sleep maintenance, and early morning awakening), interference with daytime functioning, how noticeable the impairment is to others, distress or concern caused by the sleep problem(s), as well as satisfaction with the current sleep pattern on a 5-point Likert scale. The ISI's total score ranges from 0 (not clinically significant) to 28 (clinically significant)

Insomnia will be measured by the Insomnia Severity Index (ISI) score. Participants rate the severity of sleep problems (e.g. problems with sleep onset, sleep maintenance, and early morning awakening), interference with daytime functioning, how noticeable the impairment is to others, distress or concern caused by the sleep problem(s), as well as satisfaction with the current sleep pattern on a 5-point Likert scale. The ISI's total score ranges from 0 (not clinically significant) to 28 (clinically significant)

Insomnia will be measured by the Insomnia Severity Index (ISI) score. Participants rate the severity of sleep problems (e.g. problems with sleep onset, sleep maintenance, and early morning awakening), interference with daytime functioning, how noticeable the impairment is to others, distress or concern caused by the sleep problem(s), as well as satisfaction with the current sleep pattern on a 5-point Likert scale. The ISI's total score ranges from 0 (not clinically significant) to 28 (clinically significant)

Depressive symptoms will be measured by the Patient Health Questionnaire (PHQ-8. The PHQ-8 is an 8 item 0 to 3 scale questionnaire. Total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Depressive symptoms will be measured by the Patient Health Questionnaire (PHQ-8. The PHQ-8 is an 8 item 0 to 3 scale questionnaire. Total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Depressive symptoms will be measured by the Patient Health Questionnaire (PHQ-8. The PHQ-8 is an 8 item 0 to 3 scale questionnaire. Total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Depressive symptoms will be measured by the Patient Health Questionnaire (PHQ-8. The PHQ-8 is an 8 item 0 to 3 scale questionnaire. Total score ranges from 0 (not clinically significant) to 24 (clinically significant)

The General Anxiety Disorder-7 (GAD-7) is a widely used diagnostic self-report scale that screens, diagnoses, and assesses the severity of anxiety disorder. The GAD-7 is a 7-item 0 to 3 (0 = Not at all, 3 = Nearly every day) scale that measures the degree of severity of anxiety over the last 2 weeks with a total score ranging from 0 to 21, with a higher score indicating a more severe anxiety.

The General Anxiety Disorder-7 (GAD-7) is a widely used diagnostic self-report scale that screens, diagnoses, and assesses the severity of anxiety disorder. The GAD-7 is a 7-item 0 to 3 (0 = Not at all, 3 = Nearly every day) scale that measures the degree of severity of anxiety over the last 2 weeks with a total score ranging from 0 to 21, with a higher score indicating a more severe anxiety.

The General Anxiety Disorder-7 (GAD-7) is a widely used diagnostic self-report scale that screens, diagnoses, and assesses the severity of anxiety disorder. The GAD-7 is a 7-item 0 to 3 (0 = Not at all, 3 = Nearly every day) scale that measures the degree of severity of anxiety over the last 2 weeks with a total score ranging from 0 to 21, with a higher score indicating a more severe anxiety.

The General Anxiety Disorder-7 (GAD-7) is a widely used diagnostic self-report scale that screens, diagnoses, and assesses the severity of anxiety disorder. The GAD-7 is a 7-item 0 to 3 (0 = Not at all, 3 = Nearly every day) scale that measures the degree of severity of anxiety over the last 2 weeks with a total score ranging from 0 to 21, with a higher score indicating a more severe anxiety.

The Perceived Stress Scale (PSS) is a widely used self-reported 10-item questionnaire that assesses how stressful participants believe their life is. Scores range from 0 - 40 with higher scores pointing to more perceived stress.

The Perceived Stress Scale (PSS) is a widely used self-reported 10-item questionnaire that assesses how stressful participants believe their life is. Scores range from 0 - 40 with higher scores pointing to more perceived stress.

The Perceived Stress Scale (PSS) is a widely used self-reported 10-item questionnaire that assesses how stressful participants believe their life is. Scores range from 0 - 40 with higher scores pointing to more perceived stress.

The Perceived Stress Scale (PSS) is a widely used self-reported 10-item questionnaire that assesses how stressful participants believe their life is. Scores range from 0 - 40 with higher scores pointing to more perceived stress.

Change in quality of life as measured in The Short Form 12 (SF-12). The SF-12 summary scores range from 0-100 with higher scores representing better self-reported health.

Change in quality of life as measured in The Short Form 12 (SF-12). The SF-12 summary scores range from 0-100 with higher scores representing better self-reported health.

Change in quality of life as measured in The Short Form 12 (SF-12). The SF-12 summary scores range from 0-100 with higher scores representing better self-reported health.

Change in quality of life as measured in The Short Form 12 (SF-12). The SF-12 summary scores range from 0-100 with higher scores representing better self-reported health.

Daytime sleepiness is measured by the Epworth Sleepiness Scale (ESS) The ESS total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Daytime sleepiness is measured by the Epworth Sleepiness Scale (ESS) The ESS total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Daytime sleepiness is measured by the Epworth Sleepiness Scale (ESS) The ESS total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Daytime sleepiness is measured by the Epworth Sleepiness Scale (ESS) The ESS total score ranges from 0 (not clinically significant) to 24 (clinically significant)

Healthcare utilization will be reported as the number of outpatient visits with a primary care clinician or specialty care clinician.

Healthcare utilization will be reported as the number of outpatient visits with a primary care clinician or specialty care clinician.

Healthcare utilization will be reported as the number of outpatient visits with a primary care clinician or specialty care clinician.

Healthcare utilization will be reported as the number of outpatient visits with a primary care clinician or specialty care clinician.

Medication utilization will be reported as the number of medication refills for sleep and/or psychotropic medications.

Medication utilization will be reported as the number of medication refills for sleep and/or psychotropic medications.

Medication utilization will be reported as the number of medication refills for sleep and/or psychotropic medications.

Medication utilization will be reported as the number of medication refills for sleep and/or psychotropic medications.

Change in sleep efficiency, calculated as time spent sleeping divided by time spent in bed. This data is acquired from sleep diaries filled out by patient. (range 0-100%)

Change in sleep efficiency, calculated as time spent sleeping divided by time spent in bed. This data is acquired from sleep diaries filled out by patient. (range 0-100%)

Change in sleep efficiency, calculated as time spent sleeping divided by time spent in bed. This data is acquired from sleep diaries filled out by patient. (range 0-100%)

Change in sleep efficiency, calculated as time spent sleeping divided by time spent in bed. This data is acquired from sleep diaries filled out by patient. (range 0-100%)

Sleep-onset latency (SOL; min), is based on the participants sleep diary and how many minutes it took the participants to fall asleep.

Sleep-onset latency (SOL; min), is based on the participants sleep diary and how many minutes it took the participants to fall asleep.

Sleep-onset latency (SOL; min), is based on the participants sleep diary and how many minutes it took the participants to fall asleep.

Sleep-onset latency (SOL; min), is based on the participants sleep diary and how many minutes it took the participants to fall asleep.

Change in health utility score will be generated by applying the Short Form-6D algorithm to Short Form-12 responses. Utility values for SF-6D health states can fall between 0.30 and 1.0, where 1.0 represents full health and 0 represents death.

Change in health utility score will be generated by applying the Short Form-6D algorithm to Short Form-12 responses. Utility values for SF-6D health states can fall between 0.30 and 1.0, where 1.0 represents full health and 0 represents death.

Change in health utility score will be generated by applying the Short Form-6D algorithm to Short Form-12 responses. Utility values for SF-6D health states can fall between 0.30 and 1.0, where 1.0 represents full health and 0 represents death.

Change in health utility score will be generated by applying the Short Form-6D algorithm to Short Form-12 responses. Utility values for SF-6D health states can fall between 0.30 and 1.0, where 1.0 represents full health and 0 represents death.

Inclusion Criteria: • Age between 22-64 years English-speaking (both reading and writing in English required) Diagnosis of chronic insomnia Participant is willing and able to give consent and participate in study Participant has an email account or is willing to create one and a smartphone able to download the necessary applications Participant is willing and able to use the PDT, the Hugo data sharing platform and the syncable devices (e.g. Fitbit) Participant has primary care at YNHH or Mayo Clinic Exclusion Criteria: Pregnancy Shift work or family/other commitments that interfere with establishment of regular night-time sleep patterns, and if wake/sleep time is outside the ranges of 4:00h - 10:00h (wake time) and 20:00h - 02:00h (bed time) Absence of a reliable internet access and smartphone A reported diagnosis of psychosis, schizophrenia or bipolar disorder, or any medical disorders contraindicated with sleep restriction Current involvement in a non-medication treatment program for insomnia (participants are still eligible if they are taking traditional sleep medications) Those with untreated co-existing sleep conditions (e.g. sleep apnea) Those who have failed CBT for insomnia in the past

Once the study has been completed, IPD will be shared in a way which will protect patient confidentiality using a data sharing platform for research purposes

Dreyer RP, Berkowitz A, Yaggi HK, Schneeberg L, Shah ND, Emanuel L, Kolla B, Jeffery MM, Deeg M, Ervin K, Thorndike F, Ross JS. PreScription DigitaL ThErapEutic for Patients with Insomnia (SLEEP-I): a protocol for a pragmatic randomised controlled trial. BMJ Open. 2022 Aug 8;12(8):e062041. doi: 10.1136/bmjopen-2022-062041.