Determination of Optimal Sleep Treatment Elements (The DOSE Project) - DISA (DISA)

Determination of Optimal Sleep Treatment Elements (The DOSE Project) - DISA RCT

Insomnia is a widespread public health challenge considering its impact on daily life, comorbidity with other disorders, and socio-economic costs. Previous research has shown the efficacy of cognitive behavioral therapy for insomnia (CBTI), and recent research indicates that digitally delivered CBTI (eCBTI) is highly efficacious, and statistically significantly equivalent to in-person delivered CBTI (ipCBTI) for treating insomnia. However, research is limited as to how eCBTI can be integrated into general practice as a non-pharmacological alternative to hypnotics. This study aims to evaluate the feasibility, acceptability, and effectiveness of a fully automated mobile application for treating insomnia in general practice. The secondary aims are to examine effects on psychological and physical comorbidities, possible moderators and mediators of the effect of eCBTI, and cost-effectiveness.

Study Overview

• Status: Recruiting
• Conditions: Insomnia Chronic
• Intervention / Treatment: Behavioral: Digitally delivered CBTI (eCBTI)

Detailed Description

Insomnia is prevalent in the general population (10%) and particularly so among patients in general practice (30-50%), with considerable costs to the individual and society. Hypnotics, which remain the most common treatment option in general practice, are usually not curative and are associated with risks of side effects, dependence, tolerance, and increased mortality. In contrast, cognitive behavioral therapy for insomnia (CBTI) has been shown to be highly efficacious and is recommended as the first-line treatment for insomnia by organizations such as the American Academy of Sleep Medicine, the American College of Physicians, and the European Sleep Research Society.

However, the challenge remains to make CBTI available to meet population needs due to several barriers, including a limited number of trained therapists, the costs of delivering CBTI face-to-face, and physical and geographical constraints. Digitally delivered CBTI (eCBTI) has been shown to be a possible approach to overcoming these challenges, but research on the effectiveness of eCBTI in a general practice setting remains limited.

Given the current lack of non-pharmacological treatment options for insomnia in general practice and the considerable potential of eCBTI to treat insomnia, the primary aim of the proposed study is to evaluate the feasibility, acceptability, and short- and longer-term efficacy of eCBTI for the treatment of insomnia in general practice. Our secondary aims are: a) to evaluate the possible benefits of treating insomnia on psychological and physical symptoms and comorbidities, b) to explore for whom the intervention works by examining the possible moderating effects of information technology proficiency and socio-demographic, clinical, and work-related factors, c) to investigate the possible working mechanisms, including changes in sleep-related cognitions and behaviors, and d) to assess the cost-effectiveness of the intervention.

The study is designed as a cluster-randomized controlled trial, randomizing general practitioners (GPs) from three Danish regions to screen patients for insomnia and offer either hvil®, a mobile-based program for delivering CBTI (eCBTI), or care as usual to those with moderate to-severe insomnia (ISI ≥ 10). A total of 2 X 50 GPs are expected to recruit a minimum of 2 X 250 patients who will complete the intervention. The intervention lasts 10 weeks, including an initial one-week assessment period.

The primary outcome is insomnia severity, assessed with the Insomnia Severity Index (ISI). Secondary sleep diary-based outcomes include sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TiB), and sleep efficiency (SE). Secondary non-sleep outcomes include quality-of-life (QoL) and psychological and physical symptoms such as anxiety, depression, fatigue, and pain. Cost-effectiveness will be assessed using data on healthcare utilization, social benefits, and employment from Danish national registries. Outcomes will be assessed at baseline (week 0) (T1), halfway through the intervention (week 5), post-intervention (week 11) (T3), and follow-up (6 months) (T4).

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. 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.) or treatment adherence influence intervention effects.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Morten J Lopdrup, MSc; Phone Number: +45 87 16 90 52; Email: mlop@psy.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Morten Lopdrup J MSc; Phone Number: +45 87 16 90 52; Email: sov@psy.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 referred by their general practitioner
• Individuals with access to a smartphone 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
• Individuals who are unable to read Danish
• Individuals who report severe physical or psychological comorbidity with known effects on sleep (e.g., psychosis, cancer, COPD)
• Individuals who report other diagnosed sleep or circadian rhythm disorders (e.g., sleep apnea, narcolepsy)
• Individuals who are currently receiving or have recently received CBTI or eCBTI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Care as usual waitlist control; Waitlist control; care as usual coupled with generic sleep hygiene advice. Access to treatment provided after final measurement.
Experimental: Digitally delivered CBTI (eCBTI); Based on the existing consensus concerning non-pharmacological treatment of insomnia, Hvil® includes the following treatment components: sleep hygiene, sleep optimization, stimulus control therapy, deactivation/relaxation training, and cognitive therapy. Intervention duration is approximately six to nine weeks.	Behavioral: Digitally delivered CBTI (eCBTI); Based on the existing consensus concerning non-pharmacological treatment of insomnia, Hvil® includes the following treatment components: sleep hygiene, sleep optimization, stimulus control therapy, deactivation/relaxation training, and cognitive therapy. Intervention duration is approximately six to nine weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia severity	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.	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep diary outcomes	Assessed with the Consensus Sleep Diary (CSD), which measures sleep- and waking time, sleep onset latency (SOL), wakefulness after initial sleep onset (WASO), early morning awakenings (EMA), and risetime, allowing for total sleep time (TST), total time in bed (TIB), and sleep efficiency (SE) to be calculated.	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Sleep quality	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).	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Daytime fatigue	Assessed with the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-Fatigue), which covers physical fatigue, functional fatigue, and social consequences of fatigue.	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Cognitions about sleep	Assessed with the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16).	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Physical and mental functioning	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	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Psychological distress	Assessed with the Depression, Anxiety, and Stress Scales-21 (DASS-21), which evaluates the constructs depression, anxiety, and stress on sub-scales.	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Health-related well-being	Assessed with the 5-item World Health Organisation's Well-Being Index (WHO-5).	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Application usability	Assessed with the short version of the mHealth App Usability Questionnaire (MAUQ-S).	Post-treatment (approximately week 11)
Health-related quality of life	Assessed with the five-dimensional EuroQol (EQ-5D-5L), which measures self-reported health and well-being across five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, as well as overall health on a 0-100 VAS. A higher score indicates better quality of life.	Baseline (week 0), post-treatment (approximately week 11), follow-up (approximately week 37)
Socio-economic costs	Assessed with data from Danish national registers on redeemed medicine prescriptions, use of primary and secondary health care services, long-term sickness absence	Throughout the study period, from study enrollment (week 0) to follow-up at 37 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: hvil
• Other Study ID Numbers: Fort.: 2022-0367531, 2099; 148790 (Other Grant/Funding Number: TrygFonden)

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
• product manufactured in and exported from the U.S.: No