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

(CELESTE Trial)

Overseen By Sharon Ng, MS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must not be taking: Hypnotics, Opioids, CYP3A4 inhibitors, others

Disqualifiers: Severe sleep apnea, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which insomnia treatments are most effective and safe for individuals with menopause-related sleep issues. Participants will test one of three options: trazodone (a medication often used for sleep disorders), daridorexant (a medication for insomnia), or a cognitive behavioral therapy program, each lasting 12 months. The trial specifically targets those in peri- or early menopause who began experiencing sleep difficulties during this time. Participants will track their sleep using a Fitbit and a diary, with a combination of in-person and virtual check-ins. As a Phase 4 trial, the treatments are already FDA-approved and have proven effective, helping to understand their benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people who regularly use hypnotics more than 2 nights a week or those using strong CYP3A4 inhibitors or drugs that prolong the QTc interval. It's best to discuss your current medications with the trial team.

What is the safety track record for these treatments?

Research shows that cognitive behavioral therapy for insomnia (CBT-i) is generally safe for menopausal women. Studies have found that it significantly improves sleep quality and reduces insomnia severity, with no major safety issues reported.

The FDA has approved daridorexant for treating insomnia in adults. Research indicates it helps menopausal women fall asleep and stay asleep, with a good safety record in studies, suggesting it is well-tolerated.

Although the FDA has approved trazodone for depression, it is often used to treat insomnia. A review of studies found it effective for insomnia with little to no risk for most people.

Overall, research suggests that all three treatments—CBT-i, daridorexant, and trazodone—are safe options for treating insomnia in menopausal women. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for menopause-related insomnia because they offer diverse approaches to tackling sleep issues. Cognitive behavioral therapy for insomnia (CBT-i) is unique as it addresses the root causes of insomnia through behavioral changes, providing a non-drug option that can have long-lasting benefits. Trazodone, an antidepressant often used off-label for insomnia, is included for its sedative effects, offering a familiar yet effective oral option that can be adjusted for individual needs. Meanwhile, Daridorexant stands out with its novel mechanism of action as a dual orexin receptor antagonist, which targets the brain pathways responsible for wakefulness, potentially leading to more natural sleep without the grogginess associated with some other sleep aids.

What evidence suggests that this trial's treatments could be effective for menopause-related insomnia?

This trial will compare three treatments for menopause-related insomnia: cognitive behavioral therapy for insomnia (CBT-i), daridorexant, and trazodone. Research has shown that CBT-i greatly improves sleep quality and reduces insomnia symptoms in menopausal women, leading to moderate to large improvements in sleep issues and quality of life. Studies have found that daridorexant helps with falling asleep, staying asleep, and functioning during the day for menopausal women with insomnia, noticeably improving sleep and increasing overall sleep time. Trazodone, often used for insomnia, has effectively improved sleep with minimal risk in many cases and is commonly used off-label for this purpose, indicating its potential benefits for sleep problems. All three treatments in this trial show promising results in addressing menopause-related insomnia symptoms. ^{2 6 7 8 9}

Who Is on the Research Team?

Suzanne Bertisch, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for peri- and post-menopausal women experiencing insomnia. Participants will be diverse in socio-demographic backgrounds, menopause stages, and may have related conditions like sleep apnea or mood disturbances. Details on specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

Insomnia severity index score > 10

Insomnia started or worsened during peri- or early menopause

English-speaking

Exclusion Criteria

I have been diagnosed with moderate to severe restless legs syndrome but haven't received treatment.

Limited internet access

Positive urine pregnancy test at baseline visit

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive one of the three insomnia therapies (CBT-I, trazodone, or daridorexant) for 12 months

12 months

1 in-person visit, 5 virtual visits (phone calls)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive behavioral therapy for insomnia (CBT-i)
• Daridorexant
• Trazodone

Trial Overview The study compares the effectiveness of trazodone, daridorexant (both medications), and cognitive behavioral therapy for insomnia (CBT-i) over a 12-month period with one in-person visit and five virtual check-ins.

How Is the Trial Designed?

Group I: Cognitive behavioral therapy for insomnia (CBT-i) Active Control 1 Intervention

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 II: Trazodone Active Control 1 Intervention

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 III: Daridorexant Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Wake Forest University Health Sciences

Collaborator

Trials

1,432

Recruited

2,506,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Henry Ford Health System

Collaborator

Trials

334

Recruited

2,197,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11595697/

The Effectiveness of Cognitive Behavioral Therapy on ... The results consistently showed that CBT-I significantly improves sleep quality and reduces insomnia severity in menopausal women.

2. academic.oup.com academic.oup.com/sleep/article/48/Supplement_1/A249/8134943

0571 Cognitive Behavioral Therapy for Menopausal Insomnia ... CBT-MI significantly decreases menopause insomnia severity and improves vasomotor symptoms in midlife women primarily due to attenuating sleep symptoms.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999322018433

Cognitive Behavioral Therapy for Insomnia in Women ... Across studies, insomnia symptoms and sleep quality improved with moderate to large effect sizes and achieving clinically significant changes in most studies.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02092844

Cognitive Behavioral Therapy for Insomnia and Nocturnal ... This study aims to develop and evaluate a primary care-based intervention for insomnia and nocturnal hot flashes (nHF) in peri- and postmenopausal women.

5. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.7882

Comparing Cognitive Behavioral Therapy for Insomnia, Sleep ... This study evaluated whether CBTI improves daytime fatigue, energy, self-reported sleepiness, work productivity, and quality of life in postmenopausal women ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6622507/

Comparing Cognitive Behavioral Therapy for Insomnia, ... These data support CBTI and SRT as efficacious treatments to improve nighttime symptoms associated with menopausal insomnia. Yet, insomnia is a 24-hour ...

7. mdpi.com mdpi.com/2075-1729/14/11/1405

The Effectiveness of Cognitive Behavioral Therapy on ... The results consistently showed that CBT-I significantly improves sleep quality and reduces insomnia severity in menopausal women.

8. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2522398

Telephone-Based Cognitive Behavioral Therapy for ... Findings In this randomized clinical trial of 106 women, Insomnia Severity Index scores decreased 9.9 points in women receiving cognitive behavioral therapy ...

9. womensmentalhealth.org womensmentalhealth.org/posts/10647/

In Brief: Telephone-Based CBT for Menopause-Related ... According to the results published online in the May 24 issue of JAMA Internal Medicine, women in the CBT group were more than 5 times as likely to achieve good ...