CELESTE: Comparative Effectiveness Study of behavioraL and Drug-rElated inSomnia Therapies for pEri- and Post-menopausal People
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 1,000
- Locations
- 5
- Primary Endpoint
- PROMIS Sleep Disturbance T-score
Study Overview
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.
Detailed Description
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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to 62 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Trazodone (Drug)
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.
Intervention: Daridorexant (Drug)
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).
Intervention: Cognitive behavioral therapy for insomnia (CBT-i) (Behavioral)
Outcomes
Primary Outcomes
PROMIS Sleep Disturbance T-score
Time Frame: 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 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.
Secondary Outcomes
- 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))
- Number of awakenings(6 months)
- Sleep duration(6 months)
- PROMIS Depression Scale(6 months)
- PROMIS Anxiety Scale(6 months)
- PROMIS Cognitive Function Abilities Scale(6 months)
- PROMIS Anger Scale(6 months)
- PROMISE Global Health Score(6 months)
- PROMIS Fatigue Score(6 months)
- PROMIS Interest in Sexual Activity Score(6 months)
- PROMIS Satisfaction with Sex Life Score(6 months)
- Menopause-related Quality of Life(6 months)
- Work Productivity and Activity Impairment(6 months)
- Insomnia Severity Index(6 months)
- PROMIS Pain Interference(6 months)
Investigators
Suzanne M. Bertisch, MD, MPH
Associate Professor of Medicine
Brigham and Women's Hospital