Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms

What this trial studies

The goal of this clinical trial is to learn how three current insomnia therapies (trazodone, daridorexant, cognitive behavioral therapy for insomnia) compare with each other in peri- and post-menopausal women. It will also learn about the safety of the treatments. The main questions it aims to answer are: Which commonly used insomnia therapies are most effective and safe for improving insomnia symptoms in peri- and post-menopausal people? How well do the treatments work for people from different backgrounds, who are at different stages of menopause, and who have different conditions common during menopause (e.g., sleep apnea, mood disturbance, etc.)?

Conditions in scope

• Menopausal Women
• Insomnia

Interventions

• Cognitive behavioral therapy for insomnia (CBT-i) (Behavioral) — This is a program called SHUT-i and is composed of six self-guided sessions on a website over 6-9 weeks. Each session will be about 45-60 minutes long. CBT-I involves changing behaviors that cause sleep problems to persist. However, it also…
• Trazodone (Drug) — Trazodone is a heterocyclic medication that is FDA-approved for depression (starting dose 150mg). An estimated 4 in 5 trazodone prescriptions are for insomnia. Low-dose trazodone's frequent off-label use stems from a long-standing perception that trazodone is an effective and safer…
• Daridorexant (Drug) — Daridorexant is a DORA drug. Dual orexin receptor antagonists (DORAs) are the newest class of FDA-approved medications for insomnia based on efficacy data from pivotal clinical trials demonstrating their efficacy for sleep onset and maintenance. A single dose of 50…

Who can join

Women only · Ages 40 Years to 62 Years

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)

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Status & timeline

• Overall status: Recruiting
• Study type: Interventional
• Phase: PHASE4
• Start date: 2026-02-13
• Primary completion: 2031-02
• Last update posted: 2026-03-17
• First posted: 2025-08-22

Sponsor & contact

Lead sponsor: Brigham and Women's Hospital (Other)

Collaborators: Patient-Centered Outcomes Research Institute, University of Pittsburgh, University of Utah, Massachusetts General Hospital, Henry Ford Health System, Wake Forest University Health Sciences

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• PROMIS Sleep Disturbance T-score (6 Months)
  The primary outcome is PROMIS sleep disturbance, which fulfills the criteria for content validity of a patient-reported outcome with reported relevance, comprehensiveness, ease of use, and treatment responses among people with menopause-related insomnia from diverse geographic locations. Sleep disturbance is one of the most bothersome symptoms of the menopause transition and one of the top reasons health care providers report…

Related ClearedRx care

If you’re reading this trial because you have menopause symptoms now, you don’t have to wait for a trial to access evidence-based care. ClearedRx prescribes the same FDA-approved and compounded HRT products that have been studied in trials like this one for decades.