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

NCT07136415 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2025P001920
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 5

Brief Summary

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.)? What medical problems do participants have when using these treatments? Participants will: Be asked to take trazodone every night, take daridorexant every night, or participate in an online behavioral program for insomnia, for a total of 12 months. Participate in a total of one in-person visit and 7 virtual visits (phone calls) over the 12 months. Wear (and keep) a Fitbit and fill out a daily sleep diary for at least 4 weeks over the 12 months. Fill out online surveys 4 times over the 12 months.

Conditions

Menopausal Women; Insomnia

Keywords

menopause; insomnia; cognitive behavioral therapy; trazodone; daridorexant

Outcome Measures

Primary Outcomes (1)

• PROMIS Sleep Disturbance T-score

  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 women seek care. The PROMIS sleep disturbance scale will be used and the possible range of raw score is 8-40. A higher score means higher levels of sleep disturbance. Item responses are combined to yield a T-score with a population mean of 50 and standard deviation of 10.

  6 Months

Secondary Outcomes (19)

• PROMIS Sleep-related Impairment Score

  6 months

• Sleep latency (average)

  6 months

• Client Satisfaction Measure

  6 months

• Vasomotor Symptoms

  6 months

• Occurrences of events of special interest and/or adverse events

  Throughout the study duration (up to 1 year)

Study Arms (3)

Cognitive behavioral therapy for insomnia (CBT-i)

ACTIVE COMPARATOR

Participants will be asked to take part in the CBT-i program over the course of 6-9 weeks, with the option of revisiting content throughout the study duration (12 months).

Behavioral: Cognitive behavioral therapy for insomnia (CBT-i)

Trazodone

ACTIVE COMPARATOR

Participants will be asked to take trazodone (oral pill administration) for the duration of the study (12 months), with safety monitoring conducted by study staff throughout the study. Dosage adjustments may occur.

Drug: Trazodone

Daridorexant

ACTIVE COMPARATOR

Participants will be asked to take daridorexant (oral pill administration) for the duration of the study (12 months), with safety monitoring conducted by study staff throughout the study.

Drug: Daridorexant

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 includes teaching skills to teach the participant to identify thoughts and feelings that may contribute to sleep problems.

Cognitive behavioral therapy for insomnia (CBT-i)

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 sleep aid compared to other drugs despite potential risks documented in small studies. A starting dosage of 25 mg will be used. After 1 week, patients will be instructed to increase the dose as needed to 50mg if tolerated. A second dose adjustment will be made at 4 weeks. At four weeks, study staff will contact participants and review medication adherence, and a standardized checklist will be used to assess ongoing symptoms and side effects and to consider an increase in dose to 100mg.

Trazodone

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 mg (1 pill each night within 30 minutes of bedtime) was selected based on better efficacy without evidence of higher risks than the 25mg dose. However, 25mg dosage will be instructed if the participant has moderate liver impairment and/or taking a moderate CYP3A4 inhibitor.

Daridorexant

Eligibility Criteria

• Age: 40 Years - 62 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Patient-Centered Outcomes Research Institute: collaborator
• University of Pittsburgh: collaborator
• University of Utah: collaborator
• Massachusetts General Hospital: collaborator
• Henry Ford Health System: collaborator
• Wake Forest University Health Sciences: collaborator

Study Sites (5)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

RECRUITING

Henry Ford Medical Center

Novi, Michigan, 48377, United States

NOT YET RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27103, United States

NOT YET RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

University of Utah

Salt Lake City, Utah, 84108, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Cognitive Behavioral Therapy; Trazodone; daridorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridones; Pyridines

Study Officials

• Suzanne Bertisch, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sharon Ng, MS

CONTACT

617-525-7097; shng1@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 22, 2025
• Study Start: February 13, 2026
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)