Determination of Optimal Sleep Treatment Elements - MOST (DOSE)

Determination of Optimal Sleep Treatment Elements (The DOSE Project)

Previous research has shown the efficacy of (combinations of) individual components of cognitive behavioral therapy for insomnia (CBT-I), namely sleep hygiene education, sleep restriction, stimulus control therapy, deactivation/relaxation training, and cognitive therapy. However, their relative effects, i.e., their effects in direct comparison with each other, are yet to be assessed. By means of the Multiphase Optimization Strategy (MOST), this study aims to investigate the components' relative efficacy in order to identify the most effective component or combination of components for digitized treatment of chronic insomnia. A future study will verify this intervention's effect in a randomized controlled trial (RCT).

Study Overview

• Status: Active, not recruiting
• Conditions: Insomnia Chronic
• Intervention / Treatment: Behavioral: Sleep Hygiene Education; Behavioral: Cognitive Therapy; Behavioral: Relaxation Training; Behavioral: Stimulus Control Therapy; Behavioral: Sleep Optimization

Detailed Description

The DOSE Project employs the Multiphase Optimization Strategy (MOST) to evaluate the relative efficacy of the individual cognitive behavioural therapy for insomnia (CBT-I) components. The present study represents the optimization phase of MOST, which aims to identify which combination of CBT-I components produces the best expected outcome, while taking constraints, such as economy, scalability, treatment complexity, and usability, into account.

The main objectives of the DOSE Project are

1. To conduct MOST on a multi-component smartphone or web application targeting insomnia
2. To identify the components and combination of components that demonstrate the best expected obtainable outcome
3. To examine potential moderators of the effect of the individual treatment components on insomnia severity,
4. To determine which application build (i.e., combination of components) is optimal to test in a subsequent RCT.

This study employs a fractional factorial experimental design conducted with individuals experiencing moderate-to-severe insomnia. With random allocation, participants will receive a version of the application in which one or more of the five core CBT-I components (i.e., sleep hygiene education, sleep restriction, stimulus control therapy, deactivation/relaxation training, cognitive therapy) are presented in various combinations. The intervention lasts 10 weeks, including an initial one-week assessment period.

Baseline group differences (concerning socio-demographic, disease-related, and psychosocial data) will be explored to test the success of the randomization. If differences are found, sensitivity analyses will be made to evaluate their possible influence on the results. Main effects will be analysed using Mixed Linear Models (MLMs) based on the intent-to-treat sample, comparing aggregated groups of N = 2 x 320 (e.g., plus/minus sleep restriction or plus/minus sleep hygiene etc.) on all outcome variables. MLMs account for the hierarchical, non-independent nature of the data (i.e., repeated measures nested within patients and treatment conditions), testing the time*group interaction effect, reflecting the effect of treatment. Moderation analyses will evaluate whether individual differences in various baseline variables (e.g., physical function, expectations, computer proficiency, chronotype, etc.) influence intervention effects.

• Study Type: Interventional
• Enrollment (Actual): 489
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sofie Møgelberg Knutzen, MSc; Phone Number: +4524269277; Email: sofie@psy.au.dk
• Study Contact Backup: Name: Ali Amidi, PhD, MSc; Phone Number: +4587165305; Email: ali@psy.au.dk

Study Locations

• Denmark
  • Midtjylland
    • Aarhus, Midtjylland, Denmark, 8000
      • Aarhus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (≥18 years)
• Individuals who report moderate-to-severe insomnia symptoms (a score ≥10 on the Insomnia Severity Index, ISI)
• Individuals with access to a smartphone or computer with internet connection
• Individuals who report sufficient technological proficiency (e.g., ability to download apps)

Exclusion Criteria:

• Children (<18 years)
• Individuals who report mild or no clinically relevant insomnia symptoms (a score <10 on the ISI)
• Individuals who have a shift-work schedule or are on maternity/paternity leave, if this impacts their sleep quality or amount of sleep
• Individuals who are unable to read Danish
• Individuals who report severe physical or psychological comorbidity with known effects on sleep (e.g., psychosis, cardiovascular disease, cancer, COPD)
• Individuals who report other diagnosed sleep or circadian rhythm disorders (e.g., sleep apnea, narcolepsy)
• Individuals who have previously used the "Hvil®"-app

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sleep Hygiene; Administration of sleep hygiene education (single intervention)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.
Experimental: Cognitive Therapy; Administration of cognitive therapy only (single intervention)	Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.
Experimental: Relaxation Training; Administration of relaxation training only (single intervention)	Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.
Experimental: Relaxation Training, Cognitive Therapy, Sleep Hygiene; Administration of relaxation training, cognitive therapy, and sleep hygiene education (3 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.
Experimental: Stimulus Control; Administration of stimulus control therapy only (single intervention)	Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.
Experimental: Stimulus Control, Cognitive Therapy, Sleep Hygiene; Administration of stimulus control therapy, cognitive therapy, and sleep hygiene education (3 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.
Experimental: Stimulus Control, Relaxation Training, Sleep Hygiene; Administration of stimulus control therapy, relaxation training, and sleep hygiene education (3 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.
Experimental: Stimulus Control, Relaxation Training, Cognitive Therapy; Administration of stimulus control therapy, relaxation training, and cognitive therapy (3 interventions)	Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.
Experimental: Sleep Optimization; Administration of sleep optimization only (single intervention)	Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Cognitive Therapy, Sleep Hygiene; Administration of sleep optimization, cognitive therapy, and sleep hygiene education (3 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Relaxation Training, Sleep Hygiene; Administration of sleep optimization, relaxation training, and sleep hygiene education (3 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Relaxation Training, Cognitive Therapy; Administration of sleep optimization, relaxation training, and cognitive therapy (3 interventions)	Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Stimulus Control, Sleep Hygiene; Administration of sleep optimization, stimulus control therapy, and sleep hygiene education (3 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Stimulus Control, Cognitive Therapy; Administration of sleep optimization, stimulus control therapy, and cognitive therapy (3 interventions)	Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Stimulus Control, Relaxation Training; Administration of sleep optimization, stimulus control therapy, and relaxation training (3 interventions)	Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.
Experimental: Sleep Optimization, Stimulus Control, Relaxation Training, Cognitive Therapy, Sleep Hygiene; Administration of sleep optimization, stimulus control therapy, relaxation training, cognitive therapy, and sleep hygiene education (5 interventions)	Behavioral: Sleep Hygiene Education; Automated digital administration of a sleep hygiene education module via mobile or web application, lasting approximately six weeks. The aim is to identify and modify environmental and lifestyle factors that may interfere with sleep.; Behavioral: Cognitive Therapy; Automated digital administration of a cognitive therapy module via mobile or web application, lasting approximately six weeks. The aim is to identify, challenge, and modify dysfunctional beliefs about sleep.; Behavioral: Relaxation Training; Automated digital administration of a relaxation training module via mobile or web application, lasting approximately six weeks. The aim is to reduce somatic tension and limit intrusive thought processes that interfere with sleep.; Behavioral: Stimulus Control Therapy; Automated digital administration of a stimulus control therapy module via mobile or web application, lasting approximately six weeks. The aim is to strengthen associations between sleep and the sleep environment and to eliminate conditioning of non-sleep behavior and the sleep environment.; Behavioral: Sleep Optimization; Automated digital administration of a sleep optimization module via mobile or web application, lasting approximately six weeks. Based on the participant's situation and needs, sleep restriction, sleep compression, or circadian-rhythm normalization is advised and conducted. The aim is to optimise the participant's sleep efficiency.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia severity post-intervention	Assessed with the Insomnia Severity Index (ISI), with scores ranging from 0 to 28, where higher scores indicate higher insomnia severity, and a score equal to or above 10 indicates clinical significance.	11 weeks after study entry (randomization)
Insomnia severity at 6 month follow-up	Assessed with the Insomnia Severity Index (ISI), with scores ranging from 0 to 28, where higher scores indicate higher insomnia severity, and a score equal to or above 10 indicates clinical significance.	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daytime fatigue post-intervention	Assessed with the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-Fatigue), which covers physical fatigue, functional fatigue, and social consequences of fatigue.	11 weeks after study entry (randomization)
Cognitions about sleep post-intervention	Assessed with the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16).	11 weeks after study entry (randomization)
Psychological distress post-intervention	Assessed with the Depression, Anxiety, and Stress Scales-21 (DASS-21), which evaluates the constructs depression, anxiety, and stress on sub-scales.	11 weeks after study entry (randomization)
Sleep diary outcomes post-intervention	Assessed with the Consensus Sleep Diary (CSD), which measures sleep- and waking time, sleep onset latency, wakefulness after initial sleep onset, early morning awakenings, and getting-up time, allowing for total sleep time, total time in bed, and sleep efficiency to be calculated.	11 weeks after study entry (randomization)
Sleep diary outcomes at 6-month follow-up	Assessed with the Consensus Sleep Diary (CSD), which measures sleep- and waking time, sleep onset latency, wakefulness after initial sleep onset, early morning awakenings, and getting-up time, allowing for total sleep time, total time in bed, and sleep efficiency to be calculated.	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Sleep quality post-intervention	Assessed with the Pittsburgh sleep quality index (PSQI), which measures clinically derived domains of sleep difficulties (i.e., subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction).	11 weeks after study entry (randomization)
Sleep quality at 6-month follow-up	Assessed with the Pittsburgh sleep quality index (PSQI), which measures clinically derived domains of sleep difficulties (i.e., subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction).	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Daytime fatigue at 6-month follow-up	Assessed with the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-Fatigue), which covers physical fatigue, functional fatigue, and social consequences of fatigue.	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Cognitions about sleep at 6-month follow-up	Assessed with the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16).	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Physical and mental functioning post-intervention	Assessed with the Short Form Health Survey (SF-12), which addresses different aspects of emotional states and daily activities. The questionnaire allows for sub-scores for mental and physical health to be calculated based on population norms, with higher scores indicating better health.	11 weeks after study entry (randomization)
Physical and mental functioning at 6-month follow-up	Assessed with the Short Form Health Survey (SF-12), which addresses different aspects of emotional states and daily activities. The questionnaire allows for sub-scores for mental and physical health to be calculated based on population norms, with higher scores indicating better health.	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Psychological distress at 6-month follow-up	Assessed with the Depression, Anxiety, and Stress Scales-21 (DASS-21), which evaluates the constructs depression, anxiety, and stress on sub-scales.	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Health-related well-being post-intervention	Assessed with the 5-item World Health Organisation's Well-Being Index (WHO-5).	11 weeks after study entry (randomization)
Health-related well-being at 6-month follow-up	Assessed with the 5-item World Health Organisation's Well-Being Index (WHO-5).	6 months (180 days) after post-questionnaire, approximately 8,5 months after study entry (randomization).
Application usability	Assessed with the mHealth App Usability Questionnaire (MAUQ).	11 weeks after study entry (randomization)

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: TrygFonden, Denmark; Enversion A/S
• Investigators: Principal Investigator: Robert Zachariae, DMSc, MSc, Aarhus University, Aarhus University Hospital

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2016-051-000001-2099-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All individual participant data collected during the study will be made available in an irreversibly anonymized form. However, only data of those participants can be shared who have explicitly given consent to this as part of their informed consent to study participation. This means that it may not be possible to share all data underlying a certain publication.

Data will be shared exclusively for research purposes.

• IPD Sharing Time Frame: No later than six months after publication, no end date.
• IPD Sharing Access Criteria: Data will be shared exclusively with other researchers and for research purposes only. Researchers requesting the data will have to provide a methodologically sound research proposal clarifying how the data will be used and for what purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No