Randomised controlled trial on the effect of internet-delivered computerised cognitive-behavioural therapy on patients with insomnia who remain symptomatic following hypnotics: a study protocol.

Insomnia has severe consequences for health. Primary care physicians in Japan commonly provide hypnotics, which is far from optimal. The recommended treatment for insomnia is cognitive-behavioural therapy (CBT). Access to trained therapists, however, is limited. Rather than face-to-face CBT, several researchers have studied internet-delivered computerised CBT (ICBT). This paper describes the study protocol for a randomised controlled trial (RCT) to evaluate effectiveness and feasibility of our newly developed five-step ICBT as an adjunct to usual care (UC) compared with UC alone for patients with insomnia who remain symptomatic following hypnotics. This proposed exploratory RCT comprises two parallel groups (ICBT+UC and UC alone) consisting of 15 participants each (n=30) diagnosed with insomnia who remain symptomatic after pharmacotherapy. We aim to evaluate the effectiveness of six intervention weeks. The primary outcome of insomnia severity will be the Pittsburgh Sleep Quality Index (PSQI) at week 6. Secondary outcomes include sleep onset latency, total sleep time, sleep efficiency extracted from PSQI, current feeling of refreshment and perceived soundness of sleep measured using visual analogue scale, number of awakenings, anxiety by Hospital Anxiety and Depression Scale, depression by Center for Epidemiologic Studies Depression Scale and quality of life by Euro Qol-5D. All measures will be assessed at weeks 0 (baseline), 6 (postintervention) and 12 (follow-up), and intention-to-treat analysis will be applied. The statistical analysis plan has been developed considering design of field materials. This study will be conducted at the academic outpatient clinic of Chiba University Hospital, Japan. Ethics approval was granted by the Institutional Review Board of Chiba University Hospital. All participants will be required to provide written informed consent. The trial will be implemented and reported in accordance with Consolidated Standards of Reporting Trials recommendations. UMIN000021509; Pre-results.

Sato D ，Yoshinaga N ，Nagai E ，Hanaoka H ，Sato Y ，Shimizu E ... -  《BMJ Open》

Effectiveness of Internet-Delivered Computerized Cognitive Behavioral Therapy for Patients With Insomnia Who Remain Symptomatic Following Pharmacotherapy: Randomized Controlled Exploratory Trial.

In reality, pharmacotherapy still remains the most common treatment for insomnia. This study aimed to examine the effectiveness of our internet-delivered computerized cognitive behavioral therapy (ICBT) program as an adjunct to usual care (UC) compared with UC alone in patients with insomnia who remain symptomatic following hypnotics. We recruited 23 patients with insomnia who remained symptomatic following pharmacologic treatment including benzodiazepines, and we conducted an exploratory randomized controlled trial. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) at week 6 of the treatment. Secondary outcomes were sleep onset latency, total sleep time, sleep efficiency, number of awakenings, refreshment and soundness of sleep, anxiety by Hospital Anxiety and Depression Scale, depression measured by the Center for Epidemiologic Studies Depression Scale, and quality of life (QOL) measured by the EuroQol-5D. All parameters were measured at weeks 0 (baseline), 6 (postintervention), and 12 (follow-up). The adjusted mean reduction (-6.11) in PSQI at week 6 from baseline in the ICBT plus UC group was significantly (P<.001) larger than the adjusted mean reduction (0.40) in the UC alone group. Significant differences were also found in favor of ICBT plus UC for PSQI, sleep onset latency, sleep efficiency, number of awakenings, and depression at all assessment points. Refreshment, soundness of sleep, anxiety, and QOL improved by week 6 in ICBT plus UC compared with UC alone. There were no reports of adverse events in either group during the study. These results indicated that our 6-week ICBT program is an effective treatment adjunct to UC for improving insomnia and related symptoms even after unsuccessful pharmacotherapy. University Hospital Medical Information Network Clinical Trials Registry: UMIN000021509; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023545 (Archived by WebCite at http://www.webcitation. org/75tCmwnYt).

Sato D ，Yoshinaga N ，Nagai E ，Nagai K ，Shimizu E ... -  《JOURNAL OF MEDICAL INTERNET RESEARCH》

Digital cognitive-behavioural therapy application compared with zolpidem for the treatment of insomnia: protocol for an exploratory randomised controlled trial.

Insomnia is a common health problem and cognitive-behavioural therapy (CBT) is recommended as a treatment. As there is a critical shortage of CBT-trained therapists, we developed a digital CBT application (IIIP MED: Sleepy Med) as Software as a Medical Device for insomnia. This paper describes the study protocol for an exploratory randomised controlled trial (RCT) to evaluate effectiveness and safety of our developed digital CBT (dCBT) for 5 weeks compared with zolpidem tartrate for patients with insomnia disorder. This proposed multicentre exploratory RCT will be conducted at the outpatient clinic of Chiba University Hospital, Akita University Hospital and Yoyogi Sleep Disorder Center, Japan. The study population comprises two parallel groups (dCBT and zolpidem) consisting of 15 participants each (n=30 in total) diagnosed with insomnia disorder who remain symptomatic at 4 weeks after sleep hygiene education. We will evaluate the effectiveness at baseline, week 5 (post-intervention) and week 10 (follow-up). The primary outcome will be the change of subjective sleep onset latency at week 5 from baseline. Secondary outcomes include sleep-related outcomes, such as objective sleep onset latency measured by mobile electroencephalography, functional improvement during the daytime and quality of life. Ethics approval was granted by the Institutional Review Board of Chiba University Hospital (K2023001). All participants will be required to provide written informed consent. Results will be published in international journals. jRCT2032230353.

Shimizu E ，Sato D ，Hirano Y ，Ebisu H ，Kagayama Y ，Hanaoka H ... -  《BMJ Open》

Effects of e-aid cognitive behavioural therapy for insomnia (eCBTI) to prevent the transition from acute insomnia to chronic insomnia: study protocol for a randomised controlled trial.

Previous evidence suggested that online self-guided sleep intervention is efficacious in improving treatment outcomes in patients with chronic insomnia [corrected]. However, research on online sleep interventions targeting acute insomnia [corrected] has been scarce. This study aims to evaluate the effectiveness of brief e-aid cognitive behavioural therapy for insomnia (eCBTI) in preventing transition from acute insomnia to chronic insomnia [corrected]. This is a pragmatic two-arm multicentre, randomised controlled trial comparing eCBTI with treatment as usual (TAU) in outpatients. Two hundred patients with acute insomnia [corrected] (as defined by DSM-5) will be recruited. Patients will be randomly assigned to receive 1 week eCBTI via a Smartphone application, or to receive TAU. Treatment effects will be assessed at 1 week and 3 months after intervention. The primary outcome of the study, whether the eCBTI program is sufficient in preventing transition from short-term to chronic insomnia [corrected], is measured by the Insomnia Severity Index. Secondary outcome measurements include the Dysfunctional Beliefs and Attitudes about Sleep Scale, Ford Insomnia Response to Stress Test, Sleep Hygiene and Practices Scale, Pre-sleep Arousal Scale and Epworth Sleepiness Scale. Additionally, the Hospital Anxiety and Depression Scale and the Short-Form 12-Item Health Survey will be used for measurement of mood symptoms and quality of life. Ethical approval for the study has been obtained from the Ethics Committee of Southern Medical University (reference number: NFEC-2017-131). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. NCT03302455 (clinicaltrials.gov). Date of registration: October 5, 2017.

Yang Y ，Luo X ，Paudel D ，Zhang J ，Li SX ，Zhang B ... -  《BMJ Open》

Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well).

Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

Benz F ，Grolig L ，Hannibal S ，Buntrock C ，Cuijpers P ，Domschke K ，Ebert DD ，Ell J ，Janneck M ，Jenkner C ，Johann AF ，Josef A ，Kaufmann M ，Koß A ，Mallwitz T ，Mergan H ，Morin CM ，Riemann D ，Riper H ，Schmid SR ，Smit F ，Spille L ，Steinmetz L ，Van Someren EJW ，Spiegelhalder K ，Lehr D ... -  《Trials》