The study is a multicenter randomized controlled trial (RCT) comparing eCBT-I with TAU. A total of 48 patients will be randomly assigned to the eCBT-I or TAU group. Assessment will be performed at baseline (T1), one week after the 6-week intervention period (T2) and after 6-weeks follow up (T3). The total duration of participation is 14 weeks. See figure 1 for a flowchart.
Recruitment, randomisation, blinding and treatment allocation
Participants will be recruited from five outpatient rehabilitation centres spread over the Netherlands (Heliomare Rehabilitation at Wijk aan Zee, Reade at Amsterdam, Rehabilitation Friesland at Beetsterzwaag, Basalt Rehabilitation at Delft and The Hague and Adelante at Hoensbroek). Patients that are eligible based on the inclusion and exclusion criteria will be asked to participate. After informed consent is given, participants will complete the baseline measurement. Participants will then be randomly assigned to the eCBT-I or the TAU group. All participants will continue with standard rehabilitation care for various complaints, which do not specifically address insomnia. This care can include psychotherapy aimed at mood or other psychopathology, therapy aimed at cognitive functioning, physiotherapy, fitness, occupational therapy and social work. The TAU group can receive the eCBT-I after the study. Participants can leave the study at any time for any reason without consequences. In case of withdrawal, participants will be asked to still do the measurements to control for attrition bias and a new patient will be included in accordance with the procedure. The measurements and intervention are not likely to have adverse consequences. Randomization will be done by a research randomizer program (www.randomizer.org) using blocks of four participants to balance participants equal to both groups within centres. No minimization procedure will be used. See table 1 for an overview of all measurements.
Participants are eligible for inclusion if diagnosed with stroke or TBI and insomnia disorder according to DSM-5 criteria. Furthermore, they should be aged 18 or older and capable of using the internet. Exclusion criteria are untreated sleep apnea, current or expected treatment with a main focus on fatigue or sleep during the study, unstable medication regiments, use of medication with insomnia as side effect, alcohol or drug abuse, and a major untreated or unstable medical or psychiatric condition. Users of sleep medication will be encouraged to finish medication before enrolment or to keep intake stable during the study period.
The eCBT-I comprises six guided weekly sessions provided online, combined with two face-to-face sessions of 60-minutes and a smartphone diary-app for daily reporting of sleep times and subjective sleep quality. Each session is structured around one topic and contains specific information, assignments and testimonials of two patients with insomnia after brain injury to illustrate sleep problems and homework assignments. All participants will receive online personal feedback after each session and will be encouraged to practice daily with the provided exercises, downloadable within the eHealth intervention on a daily basis. Participants can start with the next session after they have read their personal feedback. They can contact their therapist at any time by means of the integrated email function. Participants will be encouraged to complete the diary every day by their therapist.
The eCBT-I is based on well-established CBT-I components and includes behavioural and cognitive techniques. These techniques contain sleep hygiene education, stimulus control, sleep restriction, cognitive restructuring, activation, relaxation, fatigue- and stress management. The eCBT-I has been adjusted to people with brain injury both with respect to content and the way of conveying information. Content adjustments include specific education about the nature and treatment of insomnia after brain injury, and adaptations to cognitive impairments due to brain damage. Information is given in clear and short texts and is visually supported. An option is included to allow for listening to an audio version of the texts. All sessions follow the same structure, with repetition of key points. Specific feedback suggestions for each session will be provided for the therapists.
The eCBT-I will be given by an experienced registered healthcare psychologist, trained in using the eHealth intervention. Adherence will be monitored by checking frequency of registration in the sleep diary app, time spent online, and online assignments done. For a detailed description of the intervention per week see Box 1.
Sleep outcome measures
The primary outcome measure is the change in insomnia severity measured with the Dutch version of the Insomnia Severity Index (ISI). The ISI consists of 7-items and uses a 5-point scale to measure to which extent participants experience insomnia. The total score ranges from 0 (no insomnia) to 28 (severe insomnia). A cut-off of 10 is used to indicate clinical levels of insomnia in this study, similar to other studies (19-21). The internal consistency is adequate (Cronbach’s alpha = 0.74-0.78). The ISI is selected as it is sensitive to treatment response (21, 22), and used in comparable research worldwide, including the Netherlands (19, 20). Secondary sleep outcome measures include overall sleep disturbances assessed with the Pittsburgh Sleep Quality Index (23) and the following sleep features derived from the sleep diary app: total sleep time, sleep onset latency, number of nocturnal awakenings, sleep efficiency and subjective sleep quality.
Other outcome measures
These include fatigue after acquired brain injury assessed with the Dutch Multifactor Fatigue Scale (24); anxiety and depression assessed with the Dutch version of the 14-item Hospital Anxiety and Depression Scale (25); subjective cognitive functioning measured with the Cognitive Failure Questionnaire (26); and societal participation after rehabilitation assessed with the Utrecht Scale for Evaluation of Rehabilitation – Participation (USER-Participation) covering three aspects of societal participation: frequency of participation, restriction in participation and satisfaction with participation (27).
Other study parameters
Demographical, injury related and clinical variables which may influence the treatment effect will be registered: age, gender, diagnosis, time since injury, insomnia duration, use of prescribed sleep medication, use of other medication, comorbid psychiatric and somatic disorders, educational level, and currently being employed. Possible presence of sleep apnea will be screened with the Stop-Bang questionnaire (28) in participants that have not been evaluated for its presence with the gold standard overnight polysomnography (29).
Sample size calculation
In our latest randomized trial on the effect of eCBT-I we found an intraclass correlation coefficient (within subject correlation) of r=0.54 for ISI assessments repeated across 6 weeks in 175 people suffering from insomnia. Whereas treatment effects of eCBT-I are often reported to be of moderate to large size, we preferred to be somewhat conservative and expect a somewhat smaller than moderate effect in the current patient population. Calculation of the required sample size using G*Power (30) indicated that 48 completers would provide, at a significance of alpha=0.05, sufficient power (1-beta=0.80) for a minimal detectable time-by-group interaction effect of f=0.20 (small to moderate).
Data analysis will be performed with SPSS 23 (IBM; Armonck, USA). Means and standard deviations of the demographic, injury related variables and the clinical characteristics collected at baseline will be calculated. Independent T-tests will be used to check for an imbalance between groups. Nominal variables will be checked with χ2- Tests and Ordinal variable with the Mann-Whitney Test. Statistical significance will be set at a p-value of 0.05. To accommodate likely occasional missing days, the repeated measures obtained by diaries will be analyzed with mixed effect models. The treatment effects will be examined using a repeated measures ANOVA. In the case of significant baseline imbalance, post hoc analysis of covariance (ANCOVA) will be used on the change scores of the outcome measures with baseline scores as covariates. Intention-to-treat analyses will be conducted. Additionally, a per protocol analyses will be performed. Also, we will compare the eCBT-I and TAU group with regard to the percentage of participants who have improved (reduction > 7 points on the ISI) and recovered (ISI<10). In an exploratory analysis, we will investigate whether the efficacy of the treatment varies as a function of severity of insomnia and severity, type of brain injury, and time since brain injury.