Digital CBT versus nightly trazodone versus nightly daridorexant for menopause-related insomnia

CELESTE: Comparative Effectiveness Study of behavioraL and Drug-rElated inSomnia Therapies for pEri- and Post-menopausal People

This project will see if online cognitive behavioral therapy, nightly trazodone, or nightly daridorexant helps people in peri- and post-menopause who are having insomnia.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1000 (estimated)
• Ages: 40 Years to 62 Years
• Sex: Female
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Locations: 5 sites (Boston, Massachusetts and 4 other locations)
• Trial ID: NCT07136415 on ClinicalTrials.gov

What this trial studies

This interventional Phase 4 comparative study assigns participants to one of three common insomnia treatments—digital CBT for insomnia, nightly trazodone, or nightly daridorexant—and follows them for about 12 months. Participants complete one in-person baseline visit (including surveys, urine pregnancy test, ECG, and height/weight) and seven virtual follow-up visits, wear a Fitbit around baseline, and keep sleep diaries. The trial focuses on people assigned female at birth aged about 40–62 in peri- or early post-menopause whose insomnia began or worsened during the menopausal transition, and it collects data on symptom change and safety events. The study also examines how treatment effects vary by background, menopausal stage, and common coexisting conditions such as sleep apnea or mood disturbance.

Who should consider this trial

Good fit: Ideal candidates are people assigned female at birth aged 40–62 who are in peri- or early post-menopause, have an Insomnia Severity Index >10 with insomnia that started or worsened during menopause, and can complete English- or Spanish-language study procedures.

Not a fit: People with untreated moderate-to-severe sleep apnea or restless legs syndrome, very high daytime sleepiness (Epworth >15), or other untreated sleep disorders or scheduling barriers are unlikely to be suitable or to receive benefit from the interventions in this protocol.

Why it matters

Potential benefit: If successful, the results could clarify which of these three options best improves sleep and safety for peri- and post-menopausal people, helping clinicians choose the most effective treatment.

How similar studies have performed: Cognitive behavioral therapy for insomnia is well-supported by evidence and daridorexant is an FDA-approved effective insomnia medicine, while trazodone is commonly used off-label for sleep but has less rigorous comparative data in menopausal populations, so direct head-to-head evidence in this group is limited.

Eligibility criteria

Inclusion Criteria:

* Age 40-62 years
* Assigned female sex at birth
* In peri- or early menopause, following the STRAW criteria of self-report of irregular menstrual cycle or within 5 years from the last menstrual period. When menstrual markers are absent or unreliable (e.g., hysterectomy; endometrial ablation), participants must be older than 45 years old and report hot flashes
* Insomnia severity index score \> 10 at screening
* Insomnia started or worsened during peri- or early menopause
* English or Spanish speaking (Spanish-only speaking individuals will be recruited after full development of Spanish-facing materials, which may lag initial study start)

Exclusion Criteria:

* Untreated, previously diagnosed severe sleep apnea (self-report; chart review; clinician assessment)
* Untreated, previously diagnosed moderate-severe restless legs syndrome (self-report; chart review)
* Severe daytime sleepiness (Epworth Sleepiness Scale \> 15) at screening
* Sleep schedule issues that would impact effectiveness of the interventions (e.g., night shift workers with \>1 night shift/week; main sleep period outside of 8pm - 11am)
* Regular use of hypnotics \> 2 nights/week
* Limited internet access
* Pregnant or lactating or positive urine pregnancy test at baseline visit
* Prolonged QTc interval (\>460 ms) (by study baseline electrocardiogram (EKG) or EKG report in medical record)
* History of the following health conditions: Uncontrolled hypertension; clinically significant heart disease such as arrhythmias requiring medication, cardiomyopathies, heart failure, clinically significant valvular heart disease, or severe coronary artery disease (unstable angina, myocardial infarction in the prior 6 months); hypersomnia or narcolepsy; bipolar disorder, severe depression, or psychosis ; seizure within the past year; use of opioids or substance use disorder; known allergy or contraindication to trazodone or daridorexant (self-report and chart review); known severe chronic liver disease (e.g. cirrhosis); end-stage renal disease on hemodialysis; other severe medical comorbidity (e.g. likely hospitalization within next 6 months or medical conditions that increase risk of participation at a study clinician's discretion)
* Use of medications such as those that: Have known potential for significantly prolonging the QT interval (i.e. antiarrhythmics such as amiodarone, sotalol, quinidine, procainamide, dofetilide, and ibutilide), are strong CYP3A4 inhibitors, or are moderate or strong CYP3A4 inducers
* Use of one of the interventions in the past 6 months
* Other conditions determined by the PI or study clinician to preclude study participation

Where this trial is running

Boston, Massachusetts and 4 other locations

• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• Henry Ford Medical Center — Novi, Michigan, United States (Not_yet_recruiting)
• Atrium Health Wake Forest Baptist — Winston-Salem, North Carolina, United States (Not_yet_recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Not_yet_recruiting)
• University of Utah — Salt Lake City, Utah, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Suzanne Bertisch, MD, MPH — Brigham and Women's Hospital
• Study coordinator: Sharon Ng, MS

Conditions Menopausal Women; Insomnia; menopause; insomnia; cognitive behavioral therapy; trazodone; daridorexant