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

NCT ID: NCT07136415

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2031-02-28

Brief Summary

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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 6 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 5 times over the 12 months.

Detailed Description

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Insomnia, or trouble sleeping, is common. It affects about 1 in 10 adults. People with insomnia are not happy with how long or how well they sleep. Insomnia has been linked to a higher risk of depression, heart disease, memory problems, and lower quality of life. It can also lead to missing work and having accidents. Sleep problems like insomnia are also common or people going through perimenopause and post-menopause.

CBT-I teaches people to change behaviors and thoughts that make it hard to sleep. Daridorexant is an FDA-approved medicine for insomnia. Trazodone is FDA-approved to treat depression, but many doctors also prescribe it to help with sleep. This is called off-label use, which means it is used for a purpose the FDA has not officially approved. Studies show that trazodone is one of the most common medicines prescribed for insomnia in the United States.

We do not yet know how well CBT-I, trazodone, and daridorexant compare, especially for people in perimenopause and post-menopause. Throughout the duration of the study, the participant will be given one of the three therapies.

This study takes about 12 months to complete for each participant.

The following visits and procedures will happen:

Consent telephone or virtual call

Screening Visit: Baseline surveys, urine pregnancy test, electrocardiogram, height and weight assessment. The 7 days after this visit, the participant will also be asked to wear their Fitbit for 24 hours every day, fill out diaries in the morning and night, and wear a home sleep apnea test for one night.

Randomization Call: The participant will be randomized (like a flip of a coin) to receive one of the three insomnia therapies (CBT-I, trazodone, or daridorexant) a week after their baseline visit.

1-week and 4-weeks Call: Quick phone call with study staff for any study treatment adjustments.

3-Months and 6-Months Call/Visit: Fill out surveys. At 6-months, weight will be measured. The 7 days after these visits, the participant will also be asked to wear their Fitbit for 24 hours every day and fill in a sleep diary in the morning and night.

9-Months Call: Quick phone call with study staff to see if there are any issues.

12-Months Call/Visit: Fill out surveys. The 7 days after these visits, the participant will also be asked to wear their Fitbit for 24 hours every day and fill in a sleep diary in the morning and night. The Fitbit is for the participant to keep and does not have to be returned.

Conditions

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Menopausal Women Insomnia

Keywords

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menopause insomnia cognitive behavioral therapy trazodone daridorexant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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).

Group Type ACTIVE_COMPARATOR

Cognitive behavioral therapy for insomnia (CBT-i)

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Trazodone

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Daridorexant

Intervention Type 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.

Interventions

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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.

Intervention Type BEHAVIORAL

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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. In the absence of a reliable menstrual marker (e.g., hysterectomy; endometrial ablation), participants must be older than 45 years old and report hot flashes
* Insomnia severity index score \> 10
* Insomnia started or worsened during peri- or early menopause
* English-speaking

Exclusion Criteria

* Untreated, previously diagnosed severe sleep apnea (self-report; chart review)
* Untreated, previously diagnosed moderate-severe restless legs syndrome (self-report; chart review)
* Severe daytime sleepiness (Epworth Sleepiness Scale \> 15)
* Likelihood of limited benefit (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
* Positive urine pregnancy test at baseline visit
* Prolonged QTc interval (\>460 ms) (by study baseline electrocardiogram (EKG) or most recent EKG report in medical record)
* History of uncontrolled hypertension or 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)
* Use of antiarrhythmics that prolong QTc interval severely (i.e. amiodarone, sotalol, quinidine, procainamide, dofetilide, and ibutilide).
* Known severe chronic liver disease (e.g. cirrhosis)
* History of hypersomnia, narcolepsy, bipolar disorder or psychosis, severe depression, seizure within the past year, use of opioids/substance abuse disorder, pregnant or lactating, , use of strong CYP3A4 inhibitors , use of moderate or strong CYP3A4 inducers, end-stage renal disease on hemodialysis, known allergy to trazodone or daridorexant (self-report and chart review) or other medical condition that increases risk of participation at a study physician's discretion.
* Use of one of the interventions in the past 6 months
* Severe medical comorbidity (e.g., End Stage Renal Disease, likely hospitalization within next 6 months)
* Other conditions determined by the PI to preclude study participation
Minimum Eligible Age

40 Years

Maximum Eligible Age

62 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Henry Ford Health System

OTHER

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Suzanne M. Bertisch, MD, MPH

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Suzanne Bertisch, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

Central Contacts

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Sharon Ng, MS

Role: CONTACT

Phone: 617-525-7097

Email: [email protected]

Facility Contacts

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Sharon Ng, MS

Role: primary

Other Identifiers

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2025P001920

Identifier Type: -

Identifier Source: org_study_id