Recruiting

Trazodone, Daridorexant, CBT-I

Sponsor:

Brigham and Women's Hospital

Code:

NCT07136415

Conditions

Menopausal Women

Insomnia

Eligibility Criteria

Sex: Female

Age: 40 - 62

Healthy Volunteers: Not accepted

Interventions

Cognitive behavioral therapy for insomnia (CBT-i)

Trazodone

Daridorexant

Study Details

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

Study ID

NCT07136415

Start date

Feb 13, 2026

Status verified date

Jun, 2026

Completion date

Feb, 2031

Anticipated

Primary completion date

Feb, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 40 - 62

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

1000 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Cognitive behavioral therapy for insomnia (CBT-i)

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).

active comparator: Trazodone

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.

active comparator: Daridorexant

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.

Interventions

Cognitive behavioral therapy for insomnia (CBT-i)

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.

Trazodone

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.

Daridorexant

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.

Primary outcome measure

  • PROMIS Sleep Disturbance T-score [ Time Frame: 6 Months ]

Central Contacts and Locations

Central contacts

Sharon Ng, MS

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

Locations

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02120

Contacts

Sharon Ng, MS

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

Principal Investigator:

Suzanne Bertisch, MD, MPH

Henry Ford Medical Center

Recruiting

Novi, Michigan, United States, 48377

Contacts

Heba Afaneh

248-344-7363hafaneh1@hfhs.org

Principal Investigator:

Christopher Drake, PhD

University of Pittsburgh Medical Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contacts

Molly Hundertmark

412-330-1453hundertmarkmr2@upmc.edu

Principal Investigator:

Sanjay Patel, MD

University of Utah

Recruiting

Salt Lake City, Utah, United States, 84108

Contacts

Alesia Booth

801-585-1767alesia.booth@hsc.utah.edu

Principal Investigator:

Kelly Baron, PhD, MPH

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Jun 8, 2026

Last verified

Jun, 2026

Keywords

  • menopause
  • insomnia
  • cognitive behavioral therapy
  • trazodone
  • daridorexant

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2026-06-08.