A Digital Therapeutic to Improve Insomnia in Multiple Sclerosis: A Randomized Controlled Trial.

Assessed with the Insomnia Severity Index (ISI), a 7-item questionnaire for the severity of insomnia symptoms the last 14 days. Each item is rated on a 0 to 4 rating scale with higher scores indicating more severe symptoms. The ISI has good psychometric properties and is validated for online use. Range is 0-28 with higher values represent higher levels of insomnia symptom severity.

While between-group difference on the ISI on week 9 is our primary endpoint, we will also assess between group differences on the ISI at week 33 (six months after post-assessment) and week 61 (one year after post assessment). Assessed with the Insomnia Severity Index (ISI), a 7-item questionnaire for the severity of insomnia symptoms the last 14 days. Each item is rated on a 0 to 4 rating scale with higher scores indicating more severe symptoms. The ISI has good psychometric properties and is validated for online use. Range is 0-28 with higher values represent higher levels of insomnia symptom severity.

While between-group difference on the ISI on week 9 is our primary endpoint, we will also assess between group differences on the ISI at week 33 (six months after post-assessment) and week 61 (one year after post assessment). Assessed with the Insomnia Severity Index (ISI), a 7-item questionnaire for the severity of insomnia symptoms the last 14 days. Each item is rated on a 0 to 4 rating scale with higher scores indicating more severe symptoms. The ISI has good psychometric properties and is validated for online use. Range is 0-28 with higher values represent higher levels of insomnia symptom severity.

Assessed with the Consensus Sleep Dairy (sleep-onset latency [SOL]; wake-time after sleep onset [WASO]; sleep efficiency [SE]; total sleep time [TST]; sleep quality [SQ]), which will be completed by the participant at baseline and each follow-up point for at least 10 out of 14 consecutive days.

Assessed with the Consensus Sleep Dairy (sleep-onset latency [SOL]; wake-time after sleep onset [WASO]; sleep efficiency [SE]; total sleep time [TST]; sleep quality [SQ]), which will be completed by the participant at baseline and each follow-up point for at least 10 out of 14 consecutive days.

Assessed with the Consensus Sleep Dairy (sleep-onset latency [SOL]; wake-time after sleep onset [WASO]; sleep efficiency [SE]; total sleep time [TST]; sleep quality [SQ]), which will be completed by the participant at baseline and each follow-up point for at least 10 out of 14 consecutive days.

Assessed with the Outcome Questionnaire - 45.2 (OQ-45.2), a 45 item self-report scale for mental health status, specifically designed for patient progress throughout therapy. It has excellent internal consistency and is highly correlated with well-known outcomes such as the Symptom Checklist 90R, Beck Depression Inventory, The State Trait Inventory, The inventory of interpersonal problems, The Social Adjustment Scale, and the SF-36.34 The scale is scored on a scale of 0 (=never) to 5 (=almost always) giving a range of 0 to 180, with higher scores indicating higher levels of psychopathology. The OQ-45.2 has three validated subscales: symptom distress, interpersonal relations, and social role functioning (perceived level of difficulties in the workplace, school or home duties). Results will be reported for the sum score, and for the three subscales. The OQ-45.2 has an established clinical cut-off value and reliable change index

Assessed with the Outcome Questionnaire - 45.2 (OQ-45.2), a 45 item self-report scale for mental health status, specifically designed for patient progress throughout therapy. It has excellent internal consistency and is highly correlated with well-known outcomes such as the Symptom Checklist 90R, Beck Depression Inventory, The State Trait Inventory, The inventory of interpersonal problems, The Social Adjustment Scale, and the SF-36.34 The scale is scored on a scale of 0 (=never) to 5 (=almost always) giving a range of 0 to 180, with higher scores indicating higher levels of psychopathology. The OQ-45.2 has three validated subscales: symptom distress, interpersonal relations, and social role functioning (perceived level of difficulties in the workplace, school or home duties). Results will be reported for the sum score, and for the three subscales. The OQ-45.2 has an established clinical cut-off value and reliable change index

Assessed with the Outcome Questionnaire - 45.2 (OQ-45.2), a 45 item self-report scale for mental health status, specifically designed for patient progress throughout therapy. It has excellent internal consistency and is highly correlated with well-known outcomes such as the Symptom Checklist 90R, Beck Depression Inventory, The State Trait Inventory, The inventory of interpersonal problems, The Social Adjustment Scale, and the SF-36.34 The scale is scored on a scale of 0 (=never) to 5 (=almost always) giving a range of 0 to 180, with higher scores indicating higher levels of psychopathology. The OQ-45.2 has three validated subscales: symptom distress, interpersonal relations, and social role functioning (perceived level of difficulties in the workplace, school or home duties). Results will be reported for the sum score, and for the three subscales. The OQ-45.2 has an established clinical cut-off value and reliable change index

Assessed with the Outcome Questionnaire - 45.2 (OQ-45.2), a 45 item self-report scale for mental health status, specifically designed for patient progress throughout therapy. It has excellent internal consistency and is highly correlated with well-known outcomes such as the Symptom Checklist 90R, Beck Depression Inventory, The State Trait Inventory, The inventory of interpersonal problems, The Social Adjustment Scale, and the SF-36.34 The scale is scored on a scale of 0 (=never) to 5 (=almost always) giving a range of 0 to 180, with higher scores indicating higher levels of psychopathology. The OQ-45.2 has three validated subscales: symptom distress, interpersonal relations, and social role functioning (perceived level of difficulties in the workplace, school or home duties). Results will be reported for the sum score, and for the three subscales. The OQ-45.2 has an established clinical cut-off value and reliable change index

Assessed with the Hospital Anxiety and Depression Scale (HADS), a 14-item questionnaire for non-vegetative symptoms of anxiety and depression on a 0 to 3 likert scale. The sum score can be used as a measure of general psychological distress and is widely used in the community, general practice and psychiatric settings. It has a range of 0 to 42 points with higher scores indicating higher levels of psychological distress.

Assessed with the Hospital Anxiety and Depression Scale (HADS), a 14-item questionnaire for non-vegetative symptoms of anxiety and depression on a 0 to 3 likert scale. The sum score can be used as a measure of general psychological distress and is widely used in the community, general practice and psychiatric settings. It has a range of 0 to 42 points with higher scores indicating higher levels of psychological distress.

Assessed with the Hospital Anxiety and Depression Scale (HADS), a 14-item questionnaire for non-vegetative symptoms of anxiety and depression on a 0 to 3 likert scale. The sum score can be used as a measure of general psychological distress and is widely used in the community, general practice and psychiatric settings. It has a range of 0 to 42 points with higher scores indicating higher levels of psychological distress.

Assessed with the Hospital Anxiety and Depression Scale (HADS), a 14-item questionnaire for non-vegetative symptoms of anxiety and depression on a 0 to 3 likert scale. The sum score can be used as a measure of general psychological distress and is widely used in the community, general practice and psychiatric settings. It has a range of 0 to 42 points with higher scores indicating higher levels of psychological distress.

Assessed with the Chalder Fatigue Questionnaire (CFQ), a 11-item questionnaire for daytime physical and psychological fatigue on a 0 to 3 likert scale (0=less than usual, 3=much more than usual). The scale has a range of 0 to 33 with higher scores indicating higher levels of fatigue. Two additional items assess duration of fatigue (0=less than a week, 4=six months or more) and how much of the time the individual experience fatigue (0=25% of the time, 3=all the time)

Assessed with the Chalder Fatigue Questionnaire (CFQ), a 11-item questionnaire for daytime physical and psychological fatigue on a 0 to 3 likert scale (0=less than usual, 3=much more than usual). The scale has a range of 0 to 33 with higher scores indicating higher levels of fatigue. Two additional items assess duration of fatigue (0=less than a week, 4=six months or more) and how much of the time the individual experience fatigue (0=25% of the time, 3=all the time)

Assessed with the Chalder Fatigue Questionnaire (CFQ), a 11-item questionnaire for daytime physical and psychological fatigue on a 0 to 3 likert scale (0=less than usual, 3=much more than usual). The scale has a range of 0 to 33 with higher scores indicating higher levels of fatigue. Two additional items assess duration of fatigue (0=less than a week, 4=six months or more) and how much of the time the individual experience fatigue (0=25% of the time, 3=all the time)

Assessed with the Chalder Fatigue Questionnaire (CFQ), a 11-item questionnaire for daytime physical and psychological fatigue on a 0 to 3 likert scale (0=less than usual, 3=much more than usual). The scale has a range of 0 to 33 with higher scores indicating higher levels of fatigue. Two additional items assess duration of fatigue (0=less than a week, 4=six months or more) and how much of the time the individual experience fatigue (0=25% of the time, 3=all the time)

Assessed with the Fatigue Severity Scale (FSS), a 9-item questionnaire with statements about physical, social and cognitive effects of fatigue on a 1 to 7 likert scale (1=strongly disagree, 7=strongly agree). Higher total scores indicate higher levels of fatigue.

Assessed with the Fatigue Severity Scale (FSS), a 9-item questionnaire with statements about physical, social and cognitive effects of fatigue on a 1 to 7 likert scale (1=strongly disagree, 7=strongly agree). Higher total scores indicate higher levels of fatigue.

Assessed with the Fatigue Severity Scale (FSS), a 9-item questionnaire with statements about physical, social and cognitive effects of fatigue on a 1 to 7 likert scale (1=strongly disagree, 7=strongly agree). Higher total scores indicate higher levels of fatigue.

Assessed with the Fatigue Severity Scale (FSS), a 9-item questionnaire with statements about physical, social and cognitive effects of fatigue on a 1 to 7 likert scale (1=strongly disagree, 7=strongly agree). Higher total scores indicate higher levels of fatigue.

Assessed with the home-based cognitive test battery Memoro. At baseline the test battery includes subtests for assessing reaction time, spatial memory, working memory, processing speed, attention and abstract reasoning.

Assessed with the home-based cognitive test battery Memoro. At follow-up the test battery includes the subtests Coding (The Symbol Digit Modalities Test) assessing processing speed and a continuous performance test assessing attention and cognitive control function. Cognitive performance will be assessed with reaction time, number of errors and performance variability (standard deviations of hit reaction times).

Assessed with the home-based cognitive test battery Memoro. At follow-up the test battery includes the subtests Coding (The Symbol Digit Modalities Test) assessing processing speed and a continuous performance test assessing attention and cognitive control function. Cognitive performance will be assessed with reaction time, number of errors and performance variability (standard deviations of hit reaction times).

Assessed with the home-based cognitive test battery Memoro. At follow-up the test battery includes the subtests Coding (The Symbol Digit Modalities Test) assessing processing speed and a continuous performance test assessing attention and cognitive control function. Cognitive performance will be assessed with reaction time, number of errors and performance variability (standard deviations of hit reaction times).

Sleep and daytime activity will be recorded using actigraphy (GENEactiv Original, Activinsights Ltd, Kimbolton, United Kingdom). This will primarily allow collection of data to assess details of sleep-wake cycles as well as adherence to the intervention. It will also allow assessment of any intervention-related changes in daytime activity patterns and novel use of mathematical modelling.

Number of appointments at mental health care clinics, type and timing of treatment and admissions, and date of the first appointment for each patient during the study period from the Norwegian Patient Registry

Number of appointments at mental health care clinics, type and timing of treatment and admissions, and date of the first appointment for each patient during the study period from the Norwegian Patient Registry

Number of appointments at mental health care clinics, type and timing of treatment and admissions, and date of the first appointment for each patient during the study period from the Norwegian Patient Registry

Dose, timing, and type of prescribed hypnotic, sedative/anxiolytic, antidepressant and other psychotropic medications and medications used in treatment of MS (According to the WHO Anatomical Therapeutic Chemical Classification System) and changes recorded during the RCT (data from the Norwegian Prescription Database

Dose, timing, and type of prescribed hypnotic, sedative/anxiolytic, antidepressant and other psychotropic medications and medications used in treatment of MS (According to the WHO Anatomical Therapeutic Chemical Classification System) and changes recorded during the RCT (data from the Norwegian Prescription Database

Dose, timing, and type of prescribed hypnotic, sedative/anxiolytic, antidepressant and other psychotropic medications and medications used in treatment of MS (According to the WHO Anatomical Therapeutic Chemical Classification System) and changes recorded during the RCT (data from the Norwegian Prescription Database

Data from the database named 'Kontroll og Utbetaling av Helserefusjon'

Data from the database named 'Kontroll og Utbetaling av Helserefusjon'

Data from the database named 'Kontroll og Utbetaling av Helserefusjon'

Data from the administrative database called Forløpsdatabasen

Data from the administrative database called Forløpsdatabasen

Data from the administrative database called Forløpsdatabasen

Disability status assessed with the Extended Disability Status Scale from the Norwegian MS registry, information about previous and current treatment for MS, previous attack phases, first diagnosis of MS from the Norwegian MS registry.

Disability status assessed with the Extended Disability Status Scale from the Norwegian MS registry, information about previous and current treatment for MS, previous attack phases, first diagnosis of MS from the Norwegian MS registry.

Disability status assessed with the Extended Disability Status Scale from the Norwegian MS registry, information about previous and current treatment for MS, previous attack phases, first diagnosis of MS from the Norwegian MS registry.

Assessed with the Epworth Sleepiness Scale, a eight item questionnaire. The eight items represent real-life situations where the participants must rate their chance of dozing off using a 4-point scale from 0 to 3. Higher scores indicate higher chance of dozing off. Total score indicates the extent of self-reported sleep propensity.

Assessed with the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), a 16-item self-reported instrument of subjective cognitive dysfunctions including executive function, processing speed, working memory, verbal learning and memory, attention/concentration and mental tracking. Items are rated using a 4-point scale. The higher the score, the more subjective complaints. Although the assessment was initially introduced for use with individuals with bipolar disorders, the rating can be used in other clinical populations

Assessed with the Behavior Rating Inventory of Executive Function for Adults, a 75 item questionnaire that that captures views of an adult's executive functions or self-regulation in his or her everyday environment. Items are rated on a 3-point scale (Never a problem - sometimes a problem - often a problem).

Assessed with the Behavior Rating Inventory of Executive Function for Adults, a 75 item questionnaire that that captures views of an adult's executive functions or self-regulation in his or her everyday environment. Items are rated on a 3-point scale (Never a problem - sometimes a problem - often a problem).

Assessed with the Behavior Rating Inventory of Executive Function for Adults, a 75 item questionnaire that that captures views of an adult's executive functions or self-regulation in his or her everyday environment. Items are rated on a 3-point scale (Never a problem - sometimes a problem - often a problem).

Assessed with the Behavior Rating Inventory of Executive Function for Adults, a 75 item questionnaire that that captures views of an adult's executive functions or self-regulation in his or her everyday environment. Items are rated on a 3-point scale (Never a problem - sometimes a problem - often a problem).

Assessed with the Patient-Determined Disease Steps (PDDS), a questionnaire where the participants are asked to choose one out of nine alternatives that bests describes their current disability status

Feelings of state fatigue assessed with a single question (i.e "How much fatigue do you feel right now"). The participants are asked to rate their feelings of fatigue on a 4-point scale from 0=no fatigue, to 4=severe fatigue right before cognitive testing and immediately after cognitive testing.

Feelings of state fatigue assessed with a single question (i.e "How much fatigue do you feel right now"). The participants are asked to rate their feelings of fatigue on a 4-point scale from 0=no fatigue, to 4=severe fatigue right before cognitive testing and immediately after cognitive testing.

Feelings of state fatigue assessed with a single question (i.e "How much fatigue do you feel right now"). The participants are asked to rate their feelings of fatigue on a 4-point scale from 0=no fatigue, to 4=severe fatigue right before cognitive testing and immediately after cognitive testing.

Feelings of state fatigue assessed with a single question (i.e "How much fatigue do you feel right now"). The participants are asked to rate their feelings of fatigue on a 4-point scale from 0=no fatigue, to 4=severe fatigue right before cognitive testing and immediately after cognitive testing.

Perceived performance after cognitive testing will be assessed with a single question (i.e. How did you feel like you performed on the test?) rated on a 10-point scale (1=very bad, 10=very good performance)

Perceived performance after cognitive testing will be assessed with a single question (i.e. How did you feel like you performed on the test?) rated on a 10-point scale (1=very bad, 10=very good performance)

Perceived performance after cognitive testing will be assessed with a single question (i.e. How did you feel like you performed on the test?) rated on a 10-point scale (1=very bad, 10=very good performance)

Perceived performance after cognitive testing will be assessed with a single question (i.e. How did you feel like you performed on the test?) rated on a 10-point scale (1=very bad, 10=very good performance)

Perceived exertion after cognitive testing will be assessed with a single question (i.e. How much exertion did you feel during the test?) rated on a 10-point scale (1=no exertion at all, 10=very much exertion)

Perceived exertion after cognitive testing will be assessed with a single question (i.e. How much exertion did you feel during the test?) rated on a 10-point scale (1=no exertion at all, 10=very much exertion)

Perceived exertion after cognitive testing will be assessed with a single question (i.e. How much exertion did you feel during the test?) rated on a 10-point scale (1=no exertion at all, 10=very much exertion)

Perceived exertion after cognitive testing will be assessed with a single question (i.e. How much exertion did you feel during the test?) rated on a 10-point scale (1=no exertion at all, 10=very much exertion)

Assessed with the Bergen Insomnia Scale (BIS). BIS comprises six items that assesses symptoms of insomnia based on the insomnia criteria found in the Diagnostic and Statistical Manual of Mental Disorders-IVTR (American Psychiatric Association).

Assessed with the Bergen Insomnia Scale (BIS). BIS comprises six items that assesses symptoms of insomnia based on the insomnia criteria found in the Diagnostic and Statistical Manual of Mental Disorders-IVTR (American Psychiatric Association).

Assessed with the Bergen Insomnia Scale (BIS). BIS comprises six items that assesses symptoms of insomnia based on the insomnia criteria found in the Diagnostic and Statistical Manual of Mental Disorders-IVTR (American Psychiatric Association).

Assessed with the Bergen Insomnia Scale (BIS). BIS comprises six items that assesses symptoms of insomnia based on the insomnia criteria found in the Diagnostic and Statistical Manual of Mental Disorders-IVTR (American Psychiatric Association).

Presence of pain beyond everyday mundane pain, that have lasted longer than 3 months will be assessed with a single yes/no question. Location of pain will be assessed with a pain map, and levels of pain will be assessed with a 11-point numeric rating scale (0 = no pain to 10= severe pain.)

Assessed with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), a three-item self-report questionnaire assessing frequency of alcohol use (0=never, 4=four times each week or more), number of units typical for a drinking day (0=1-2 units, 4=10 or more units), and frequency of binge-drinking (0=never, 4=daily or almost daily). It is a short-version of the 10-item AUDIT developed by the World Health Organization

Assessed with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), a three-item self-report questionnaire assessing frequency of alcohol use (0=never, 4=four times each week or more), number of units typical for a drinking day (0=1-2 units, 4=10 or more units), and frequency of binge-drinking (0=never, 4=daily or almost daily). It is a short-version of the 10-item AUDIT developed by the World Health Organization

Assessed with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), a three-item self-report questionnaire assessing frequency of alcohol use (0=never, 4=four times each week or more), number of units typical for a drinking day (0=1-2 units, 4=10 or more units), and frequency of binge-drinking (0=never, 4=daily or almost daily). It is a short-version of the 10-item AUDIT developed by the World Health Organization

Assessed with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), a three-item self-report questionnaire assessing frequency of alcohol use (0=never, 4=four times each week or more), number of units typical for a drinking day (0=1-2 units, 4=10 or more units), and frequency of binge-drinking (0=never, 4=daily or almost daily). It is a short-version of the 10-item AUDIT developed by the World Health Organization

Assessed with the 12-Item Short Form Survey (SF-12). SF-12 The SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life, and is a measure of quality of life. The SF-12 is a shortened version of the SF-36.

Assessed with the 12-Item Short Form Survey (SF-12). SF-12 The SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life, and is a measure of quality of life. The SF-12 is a shortened version of the SF-36.

Assessed with the 12-Item Short Form Survey (SF-12). SF-12 The SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life, and is a measure of quality of life. The SF-12 is a shortened version of the SF-36.

Assessed with the 12-Item Short Form Survey (SF-12). SF-12 The SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life, and is a measure of quality of life. The SF-12 is a shortened version of the SF-36.

Assessed with Euroqol-5D, a 5-item self-report questionnaire for general health state on a 0 to 5 likert scale. It measures levels of problems with walking, performing self-care, doing usual activities, pain/discomfort, and anxiety/depression. It is widely used across Europe in assessments of health resources utilization as it allows measurement of Quality Adjusted Life Years (QALYs) in individuals presenting with a wide range of physical and mental disorders

Assessed with Euroqol-5D, a 5-item self-report questionnaire for general health state on a 0 to 5 likert scale. It measures levels of problems with walking, performing self-care, doing usual activities, pain/discomfort, and anxiety/depression. It is widely used across Europe in assessments of health resources utilization as it allows measurement of Quality Adjusted Life Years (QALYs) in individuals presenting with a wide range of physical and mental disorders

Assessed with Euroqol-5D, a 5-item self-report questionnaire for general health state on a 0 to 5 likert scale. It measures levels of problems with walking, performing self-care, doing usual activities, pain/discomfort, and anxiety/depression. It is widely used across Europe in assessments of health resources utilization as it allows measurement of Quality Adjusted Life Years (QALYs) in individuals presenting with a wide range of physical and mental disorders

Assessed with Euroqol-5D, a 5-item self-report questionnaire for general health state on a 0 to 5 likert scale. It measures levels of problems with walking, performing self-care, doing usual activities, pain/discomfort, and anxiety/depression. It is widely used across Europe in assessments of health resources utilization as it allows measurement of Quality Adjusted Life Years (QALYs) in individuals presenting with a wide range of physical and mental disorders

Assessed with the Negative Effects Questionnaire (NEQ), a self-report measure that contains 20 items that are scored on a five-point Likert-scale (rated 0-4) where higher scores indicate higher levels of negative effects. After each item, the individual is asked whether they consider the effect to be caused by the intervention received or caused by other circumstances (yes/no), as well as one open-ended question

Assessed with the Negative Effects Questionnaire (NEQ), a self-report measure that contains 20 items that are scored on a five-point Likert-scale (rated 0-4) where higher scores indicate higher levels of negative effects. After each item, the individual is asked whether they consider the effect to be caused by the intervention received or caused by other circumstances (yes/no), as well as one open-ended question

Assessed with the Use of Sleep Strategies (USS), a six item self-report questionnaire developed to measure how often individuals use six different therapeutic techniques (keep a stable rise time, refrain from sleeping during daytime, use the bed and bedroom only for sleeping, practiced sleep restriction, practiced stimulus control) and their perception of its utility. The techniques are integral to CBT-I but are also described in sleep psychoeducation or hygiene programmes

Assessed with the Use of Sleep Strategies (USS), a six item self-report questionnaire developed to measure how often individuals use six different therapeutic techniques (keep a stable rise time, refrain from sleeping during daytime, use the bed and bedroom only for sleeping, practiced sleep restriction, practiced stimulus control) and their perception of its utility. The techniques are integral to CBT-I but are also described in sleep psychoeducation or hygiene programmes

Dose, timing, and type of prescribed and unsubscribed medications

Assessed by checking of a list of 20 common medical conditions, and 9 common mental disorders

Number of physical activities per week at moderate and/or strenuous intensity, and duration of the activities

One question assessing height and one question assessing weight

Familiarity with use of the internet at baseline and electronic media use (five items) over time. These ratings will be used in subsidiary analyses as for example, how baseline skills in using the internet may affect engagement with internet interventions.

Number of previous treatments, number of prescribed medications for mental disorders

Number of previous treatments, number of prescribed medications for insomnia

One item assessing for how long the current sleep problem have lasted in years and months