Effective of Early Treatment of Insomnia on the Adherence of CPAP

2.1 Hypothesis and primary objective Our hypothesis is that concurrent treatment of insomnia with digital cognitive behavioral therapy for insomnia (CBT-I) will improve adherence to continuous positive airway pressure (CPAP) therapy in patients with COMISA. It is well-established that patients with OSAS who do not have comorbid insomnia demonstrate better adherence to CPAP therapy. By treating insomnia symptoms earlier in the course of therapy, patients may be more likely to tolerate and accept CPAP, particularly during the critical early phase when adherence habits are being formed. This may help create a more positive experience and stronger therapeutic alliance with CPAP. Additionally, patients may benefit from beginning CBT-I while they are already using CPAP, as they can tailor therapeutic strategies to their personal experience with the device, for example, by addressing specific cognitive or behavioral challenges related to mask discomfort, sleep onset latency, or nighttime awakenings.

The primary objective of this study is to assess whether initiating CBT-I at the time of CPAP prescription leads to improved treatment adherence among patients with COMISA, who are often at higher risk of non-compliance due to their insomnia symptoms.

2.2 Secondary objectives

Secondary objectives of the study are:

• To evaluate the effect of concurrent CBT-I on cardiovascular health
• To evaluate the effect of concurrent CBT-I on cognitive performance

Exploratory objectives of the study are:

• To evaluate the effect of concurrent CBT-I on sleep quality and insomnia symptoms in COMISA patients under CPAP treatment.
• To evaluate the effect of concurrent CBT-I on depression and anxiety symptoms in COMISA patients under CPAP treatment.
• To evaluate the effect of concurrent CBT-I on the residual sleepiness and fatigue under CPAP treatment.
• To evaluate the effect of concurrent CBT-I on quality of life in COMISA patients under CPAP treatment.
• To explore whether improvement in insomnia symptoms following CBT-I is associated with CPAP compliance within the CBT-I + CPAP group (comparison between participants with and without improvement in insomnia symptoms).

2.3 Primary and secondary endpoints Primary endpoint

The primary endpoint will be derived from objective data recorded by the CPAP device:

• CPAP compliance, defined as the average nightly use (in minutes) over the last 3 months, measured in the middle and end of the study.

Secondary endpoints

The following secondary outcomes will be assessed:

Sleep-related and subjective measures:

• Cognitive Failures Questionnaire 2.0 (CFQ 2.0): assessment of subjective cognitive complaints.17
• Epworth Sleepiness Scale (ESS): assessment of daytime sleepiness.18
• Pittsburgh Sleep Quality Index (PSQI): evaluation of sleep quality over a 1-month period.19
• Quebec Sleep Questionnaire (QSQ).20
• Insomnia Severity Index (ISI): assessment of insomnia severity.21
• Fatigue Severity Scale (FSS): assessment of fatigue levels.22
• Hospital Anxiety and Depression Scale (HADS): assessment of anxiety and depressive symptoms.23

Objective neurocognitive performance:

• Montreal Cognitive Assessment (MoCA): global cognitive functioning.24
• Trail Making Test (Parts A and B): attention, processing speed, and executive function.25
• Stroop Test (Victoria version): cognitive flexibility and inhibitory control.26
• Verbal Fluency Tests (phonemic and semantic/animal): verbal executive function and lexical access.27
• Free and Cued Selective Reminding Test (FCSRT): visuospatial attention and processing speed.28

Cardiovascular measures:

• 24 hours Ambulatory Blood Pressure Monitoring (ABPM) and heart rate will be recorded at baseline and at 6 months.

2.4 Study design This study will be conducted in the form of a parallel-group controlled trial, with the aim of testing the potential of early CBT-I treatment to improve CPAP adherence in COMISA patients. It is a monocentric study that will take place in Centre Hospitalier Universitaire Vaudois (CHUV), a primary teaching hospital in Lausanne, Switzerland.

In routine clinical practice at CHUV, CPAP is habitually prescribed for patients with obstructive sleep apnea. CBT-I may also be prescribed when chronic insomnia is identified; however, it is usually delivered face-to-face or in group format, with waiting times that can reach up to six months at the Centre Interdisciplinaire du Sommeil (CIRS). The key difference in the present trial compared to usual care is the immediate and simultaneous initiation of a digital CBT-I program at the time of CPAP prescription, without delay for de "Early CBT-I + CPAP group".

COMISA patients will be randomized 1:1 (60 patients in either group) to the CPAP alone (control group), or concurrent CPAP with digital CBT-I based on a random list created through an online randomisation tool: A computer-generated pseudorandom number generator will be used to produce the randomisation list.

The study consists in 3 visits for each group.

Baseline visit:

After verification of eligibility criteria, participants will provide written informed consent. Demographic data and ambulatory blood pressure monitoring (ABPM) and heart rate will be collected. Clinical data will be retrieved from earlier diagnostic visits before the study (from polygraphy or polysomnography). The following validated questionnaires will be administered:

• Epworth Sleepiness Scale (ESS)
• Quebec Sleep Questionnaire (QSQ)
• Insomnia Severity Index (ISI)
• Hospital Anxiety and Depression Scale (HADS)
• Pittsburgh Sleep Quality Index (PSQI)

A comprehensive neurocognitive assessment will then be performed, including:

• Montreal Cognitive Assessment (MoCA)
• Trail Making Test
• Stroop Test (Victoria version)
• Verbal Fluency Tests (phonemic and semantic)
• Five-Point Star Cancellation Test (FCSRT)
• Cognitive Failures Questionnaire 2.0 (CFQ 2.0) to assess subjective cognitive complaints

After all tests have been performed, team member will inform the patient as to which group they will be in and in case they will partake in dCBT-I, answer any questions they may have regarding use and installation of the application.

3-month visit: Continuous positive airway pressure (CPAP) adherence data will be collected from the CPAP device, measured as the average nightly usage over the previous 3 months. The percentage of nights with usage greater than 4 hours and the average residual AHI will also be collected from the CPAP device. All questionnaires listed above will be re-administered, except for the neurocognitive tests.

6-month visit: CPAP adherence data will again be collected from the CPAP device (average nightly usage). The percentage of nights with usage greater than 4 hours and the average residual AHI will also be collected from the CPAP device. All questionnaires will be re-administered, and all neurocognitive tests will be repeated. ABPM and heart rate will also be recorded.

2.5 Study intervention

Early digital CBT-I group (HelloBetter Insomnie + CPAP)

Participants randomized to the early intervention group will begin digital cognitive behavioral therapy for insomnia (dCBT-I) immediately after completion of all baseline assessments. The intervention will be delivered through HelloBetter Insomnie, a CE-marked (Class I, EU MDR 2017/745) digital medical device developed by GET.ON Institut für Online Gesundheitstrainings GmbH.12

HelloBetter Insomnie consists of eight structured online modules, typically completed over 10 to 12 weeks, each requiring approximately 45-60 minutes. The modules include evidence-based CBT-I content such as:

• sleep hygiene and sleep-wake scheduling
• sleep restriction therapy
• stimulus control techniques
• behavioural activation
• relaxation exercises
• strategies to address dysfunctional thoughts, cognitive rumination, and conditioned arousal
• relapse-prevention tools
• In addition to the core modules, participants have access to:
• an integrated sleep diary (agenda du sommeil)
• regular symptom check-ins
• planning tools for energising and healthy activities
• individualized goal-setting and progress monitoring
• Participants are encouraged to implement exercises in daily life between modules.

A distinctive component of the HelloBetter programme is the availability of personalised professional support: After each completed module, participants receive written feedback within 24 hours on working days from a designated clinical psychologist trained in digital CBT-I. Each participant is followed by the same psychologist throughout the programme.

Participants will begin CPAP treatment at the same time as the digital CBT-I. CPAP therapy will follow standard clinical procedures, as prescribed by the treating sleep physician, and will not be modified by the study.

CPAP only group

Participants randomized to the late intervention group will receive usual standard-of-care CPAP therapy at baseline, identical to the early intervention group, but will not have access to digital CBT-I during the 6-month study period. This reflects the current average waiting time (~6 months) for access to face-to-face CBT-I at the CHUV.

To ensure equity in access to care, all participants in the late group will be offered free access to HelloBetter Insomnie after completion of the 6-month study visit. CPAP treatment will be prescribed and followed according to standard clinical practice in both groups.

2.6 Patient and public involvement Patients with comorbid chronic insomnia and obstructive sleep apnea were informally consulted during routine clinical consultations with the principal investigator. These discussions focused in particular on access to cognitive behavioral therapy for insomnia (CBT-I), for which waiting times currently exceed six months at the Centre for Sleep Investigation and Research (CIRS).

Many patients expressed frustration regarding these delays and indicated that they would be willing to engage in a digital insomnia therapy. Several patients also reported that initiating CBT-I in close temporal proximity to the start of CPAP treatment could help them improve both their insomnia and their sleep apnea, provided that the delay between the two interventions was not too long. Digital CBT-I is recognised as a first-line treatment and is classified at the highest level of evidence in recent European guidelines for chronic insomnia29. This patient feedback directly informed the conception of the present study, particularly the evaluation of an early digital CBT-I intervention delivered in parallel with CPAP therapy, with the aim of reducing waiting times for this reference treatment and optimising outcomes for both conditions.

Patients will not be involved in the conduct of the trial, data analysis, or dissemination strategy. However, a lay summary of the study results will be provided to participants at the end of the trial.

Inclusion criteria

• 45-65 years of age
• Diagnosis of OSAS by respiratory polygraphy or polysomnography with an apnea-hypopnea index (AHI) ≥20 when scored by PSG or ≥15 when scored by PG30 with a prescription for CPAP therapy
• Diagnosis of chronic insomnia according to the International Classification of Sleep Disorders (ICSD 3-TR).31
• Ability to communicate in French
• Ability to provide informed consent
• Accept to receive information about incidental findings
• Ownership of a smartphone running at least Android 9 (API version 28+) or iOS 12.2+.

Exclusion criteria

• Current treatment for OSAS
• Current or past treatment for chronic insomnia (CBT-I)
• Severe restless legs syndrome
• REM sleep behaviour disorder
• Neurological diseases (stroke, Parkinson's disease, etc.)
• Severe hypertension (≥180 mmHg systolic or requiring ≥3 antihypertensive medications)
• Respiratory failure (oxygen saturation during wakefulness <90%)
• Severe heart failure (NYHA class III-IV)
• High-risk alcohol consumption (≥14 units/week)
• Known pregnancy
• Epilepsy or history of epileptic seizures (ICD-11: 8A6; ICD-10: G40)
• Known bipolar disorder of any type (ICD-11: 6A60, 6A61, 6A6Y, 6A6Z; ICD-10: F31)
• Known Acute and transient psychotic disorder (ICD-11: 6A23; ICD-10: F23)
• Known Active suicidal ideation
• Known or suspected severe parasomnias incompatible with programme use (e.g., sleepwalking:
• Known Severe cardiovascular disease that may contraindicate unsupervised CBT-I strategies (e.g., unstable arrhythmias, angina pectoris)
• Any medical or psychiatric condition that, in the investigator's judgment, would contraindicate the use of the CE-marked HelloBetter Insomnie digital device or participation in CBT-I