Menopausal Women, Insomnia
Conditions
Keywords
menopause, insomnia, cognitive behavioral therapy, trazodone, daridorexant
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: 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. During the visit window, 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 for a total of 7 days. 9-Months Call: Quick phone call with study staff to see if there are any issues. 12-Months Call/Visit: Fill out surveys. During the visit window, 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 for a total of 7 days. The Fitbit is for the participant to keep and does not have to be returned.
Interventions
BEHAVIORALCognitive 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.
DRUGTrazodone
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.
DRUGDaridorexant
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.
Sponsors
Brigham and Women's Hospital
Patient-Centered Outcomes Research Institute
University of Pittsburgh
University of Utah
Massachusetts General Hospital
Henry Ford Health System
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 62 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PROMIS Sleep Disturbance T-score | 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
| Measure | Time frame | Description |
|---|---|---|
| PROMIS Sleep-related Impairment Score | 6 months | Validated questionnaire assessing daytime alertness. The PROMIS sleep-related impairment scale will be used and the possible range of raw score is 8-40. A higher score means higher levels of sleep-related impairment. |
| Sleep latency (average) | 6 months | Measurement of time it takes to fall asleep after going to rest. This is measured in time units (minutes, hours) by self-report and Fitbit. This will be analyzed as a 7-day average. |
| Client Satisfaction Measure | 6 months | This is measured via the Client Satisfaction Questionnaire. Total scores range from 8 to 32, with the higher number indicating greater satisfaction. |
| Vasomotor Symptoms | 6 months | The severity and frequency of vasomotor symptoms assessed via self-report and measured by Likert scale and number of hot flashes per day/night, respectively. |
| Occurrences of events of special interest and/or adverse events | Throughout the study duration (up to 1 year) | Occurrence of events of special interest (falls, fall-related injuries, drowsiness, dizziness, headache, nausea, dry mouth, palpitations) will be measured for each arm by self-report or chart review. Occurrence of adverse events will also be assessed by number of participants with treatment-related adverse events as defined by CTCAE v4.0 |
| Number of awakenings | 6 months | Measure of number of awakenings per night by Fitbit. |
| Sleep duration | 6 months | Measured by Fitbit, in hours and minutes. |
| PROMIS Depression Scale | 6 months | The PROMIS depression scale will be used and the possible range of raw score is 8-40. A higher score means higher levels of depression symptoms. |
| PROMIS Anxiety Scale | 6 months | The PROMIS anxiety scale will be used and the possible range of raw score is 8-40. A higher score means higher levels of anxiety symptoms. |
| PROMIS Cognitive Function Abilities Scale | 6 months | The PROMIS cognitive function abilities scale will be used and the possible range of raw score is 4-20. A higher score represents better cognitive function. |
| PROMIS Anger Scale | 6 months | The PROMIS anger scale will be used and the possible range of raw score is 5-25. A higher score means higher levels of anger. |
| PROMISE Global Health Score | 6 months | The PROMIS global health scale will be used and the possible range of raw score is 8-40. A higher score indicates better physical and mental health. |
| PROMIS Fatigue Score | 6 months | The PROMIS fatigue scale will be used and the possible range of raw score is 8-40. A higher score indicates higher levels of fatigue. |
| PROMIS Interest in Sexual Activity Score | 6 months | The PROMIS interest in sexual activity scale will be used and the possible range of raw score is 2-10. A higher score indicates greater interest in sexual activity. |
| PROMIS Satisfaction with Sex Life Score | 6 months | The PROMIS satisfaction with sex life scale will be used and the possible range of raw score is 4-20. A higher score indicates higher satisfaction with sex life. |
| Menopause-related Quality of Life | 6 months | The menopause-related quality of life (MENQOL) scale will be used and the possible range of raw score is 29-232. A higher score indicates higher severity of menopause-related symptoms. |
| Work Productivity and Activity Impairment | 6 months | The Work Productivity and Activity Impairment - General Health (WPAI-GH) Questionnaire is a 6-item instrument to measure impairments over the past 7 days in both paid work and unpaid work due to one's health. Higher numbers indicate greater impairment and less productivity. Four main outcomes can be yielded from WPAI and are presented as percentages (0-100%). |
| Insomnia Severity Index | 6 months | The Insomnia Severity Index will be used and the possible range of raw score is 0-28. A higher score means more severe symptoms of insomnia. |
| PROMIS Pain Interference | 6 months | The PROMIS pain interference scale will be used and the possible range of raw score is 4-20. A higher score means higher levels of pain. |
Countries
United States
Contacts
CONTACTSharon Ng, MS
PRINCIPAL_INVESTIGATORSuzanne Bertisch, MD, MPH
Brigham and Women's Hospital
Outcome results
None listed