Actively Recruiting
Sequential Multiple Assignment Randomized Trial Comparing Commonly Prescribed and Over the Counter Medications for the Treatment of Insomnia in Adults
Led by University of Pennsylvania · Updated on 2026-06-05
1200
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
U
University of Pennsylvania
Lead Sponsor
P
Patient-Centered Outcomes Research Institute
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the effectiveness, safety, and lasting benefits of common prescription and over-the-counter medications used to treat insomnia in adults aged 18 to 80 years. The study focuses on medications including zolpidem, trazodone, melatonin, diphenhydramine, and doxepin, aiming to address the lack of clear data on which treatments offer the best balance of benefits and risks for patients with chronic insomnia. The trial responds to calls from healthcare agencies for more rigorous comparisons to guide treatment decisions in primary care. Participants will be randomly assigned to take one of these medications or a placebo nightly, 30 minutes before bed, with doses adjusted based on tolerance and response after two weeks. The study uses a double-blind, placebo-controlled design with a sequential multiple assignment approach, allowing participants who do not respond to one treatment to be re-randomized to another. All participants receive sleep hygiene education and are instructed to stay in bed for 7 to 9 hours to enhance treatment effects and safety. During the study, participants will be assessed for treatment response, side effects, and daytime symptoms over an initial one-month acute treatment phase. Those who respond will continue treatment for up to six months to evaluate longer-term benefits and safety. Assessments include sleep latency, wake after sleep onset, total sleep time, and various self-reported measures of daytime function, mood, cognition, and quality of life. The trial includes regular monitoring to track these outcomes and ensure participant safety throughout the study period.
CONDITIONS
Brief Title
A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18-80 years
- Meet DSM-5 criteria for Insomnia Disorder
- Score 15 or higher on the Insomnia Severity Index (ISI)
- Experience sleep initiation or maintenance problems lasting 30 minutes or more, at least 3 nights per week for 3 months or longer
- Willing to stop all sleep-related medications before enrollment
- Complete a 2-week washout period before starting study medication
- Provide clinician assent for participation
You will not qualify if you...
- Regular daytime napping of 1 hour or more on 3 or more days per week
- History of suicidal attempts or current suicidal thoughts
- Acute or uncontrolled psychiatric or medical conditions
- Current alcohol or drug misuse
- Diagnosed or high risk for other sleep disorders like circadian rhythm disorders or shift work sleep disorder
- Age under 18 or over 80 years
- Poor English comprehension
- Limited use of smartphones, computers, tablets, or internet
- Women who are pregnant, breastfeeding, or planning pregnancy
- Acute or unstable psychiatric illnesses
- Significant medical problems or recent acute illness
- Liver or kidney problems
- Certain medical conditions contraindicating study drugs, including epilepsy, glaucoma, urinary retention, increased eye pressure, pheochromocytoma, or porphyria
- Alcohol or substance use disorder within 2 years
- Unable to abstain from alcohol or substances for required periods
- Known allergies or contraindications to study drugs or their ingredients
- Recent use of CNS-active drugs prohibited by the protocol
- Heavy tobacco use or inability to refrain from smoking at night
- Unable or unwilling to stop certain medications that affect drug metabolism (CYP3A4 inhibitors)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 6 months, including an acute phase of 1 month and a longer-term maintenance phase of 1 to 6 months
Participants take nightly doses of study medications or placebo 30 minutes prior to bed, with possible dose increase after 2 weeks if initial response is inadequate. Treatment includes sleep hygiene education and may involve re-randomization to alternative medications for non-responders at 1 month.
Visits at baseline, 2 weeks, 1 month, and monthly follow-ups up to 6 months
Trial Site Locations
Total: 1 location
1
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
Research Team
M
Michael L Perlis, PhD
M
Mark Seewald, MSW
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
6
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