Trial Outcomes & Findings for CBT-I or Zolpidem/Trazodone for Insomnia (NCT NCT04468776)

NCT ID: NCT04468776

Last Updated: 2025-02-24

Results Overview

Change in Insomnia Severity Index score from baseline to follow-up. The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks. Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms. Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Baseline ISI, Treatment Arm, Visit and Treatment Arm\*Visit interaction. Random effects: intercept for Subject, nested within Site.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 155 participants
• Primary outcome timeframe: Baseline, 6 months
• Results posted on: 2025-02-24

Participant Flow

Participant milestones

Measure	Medication (Zolpidem or Trazodone) Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Overall Study STARTED	49	54	52
Overall Study 9 Weeks Follow-up	40	37	41
Overall Study 6 Months Follow-up	38	32	34
Overall Study 12 Months Follow-up	37	30	33
Overall Study COMPLETED	44	40	43
Overall Study NOT COMPLETED	5	14	9

Reasons for withdrawal

Measure	Medication (Zolpidem or Trazodone) Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Overall Study Lost to Follow-up	4	3	4
Overall Study Withdrawal by Subject	1	10	4
Overall Study Physician Decision	0	1	1

Baseline Characteristics

1 participant refused to report sex.

Baseline characteristics by cohort

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician	Total n=155 Participants Total of all reporting groups
Age, Continuous	55.2 years STANDARD_DEVIATION 14.6 • n=49 Participants	52.5 years STANDARD_DEVIATION 15.3 • n=54 Participants	52.5 years STANDARD_DEVIATION 15.3 • n=52 Participants	53.4 years STANDARD_DEVIATION 15.0 • n=155 Participants
Sex: Female, Male Female	37 Participants n=49 Participants • 1 participant refused to report sex.	44 Participants n=54 Participants • 1 participant refused to report sex.	37 Participants n=51 Participants • 1 participant refused to report sex.	118 Participants n=154 Participants • 1 participant refused to report sex.
Sex: Female, Male Male	12 Participants n=49 Participants • 1 participant refused to report sex.	10 Participants n=54 Participants • 1 participant refused to report sex.	14 Participants n=51 Participants • 1 participant refused to report sex.	36 Participants n=154 Participants • 1 participant refused to report sex.
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=49 Participants	0 Participants n=54 Participants	3 Participants n=52 Participants	4 Participants n=155 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=49 Participants	54 Participants n=54 Participants	49 Participants n=52 Participants	151 Participants n=155 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=49 Participants	0 Participants n=54 Participants	0 Participants n=52 Participants	0 Participants n=155 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=49 Participants	0 Participants n=54 Participants	0 Participants n=52 Participants	0 Participants n=155 Participants
Race (NIH/OMB) Asian	0 Participants n=49 Participants	1 Participants n=54 Participants	0 Participants n=52 Participants	1 Participants n=155 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=49 Participants	0 Participants n=54 Participants	0 Participants n=52 Participants	0 Participants n=155 Participants
Race (NIH/OMB) Black or African American	0 Participants n=49 Participants	3 Participants n=54 Participants	1 Participants n=52 Participants	4 Participants n=155 Participants
Race (NIH/OMB) White	47 Participants n=49 Participants	49 Participants n=54 Participants	49 Participants n=52 Participants	145 Participants n=155 Participants
Race (NIH/OMB) More than one race	1 Participants n=49 Participants	1 Participants n=54 Participants	0 Participants n=52 Participants	2 Participants n=155 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=49 Participants	0 Participants n=54 Participants	2 Participants n=52 Participants	3 Participants n=155 Participants
Region of Enrollment United States	49 participants n=49 Participants	54 participants n=54 Participants	52 participants n=52 Participants	155 participants n=155 Participants
Medication preference Zolpidem	11 Participants n=49 Participants	10 Participants n=54 Participants	11 Participants n=52 Participants	32 Participants n=155 Participants
Medication preference Trazodone	38 Participants n=49 Participants	44 Participants n=54 Participants	41 Participants n=52 Participants	123 Participants n=155 Participants
Insomnia Severity Index total score	18.1 score on a scale STANDARD_DEVIATION 4.3 • n=49 Participants	17.4 score on a scale STANDARD_DEVIATION 3.7 • n=54 Participants	18.9 score on a scale STANDARD_DEVIATION 4.2 • n=52 Participants	18.1 score on a scale STANDARD_DEVIATION 4.1 • n=155 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Change in Insomnia Severity Index score from baseline to follow-up. The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks. Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms. Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Baseline ISI, Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Insomnia Symptom Severity	-8.05 change score on a scale Interval -9.44 to -6.65	-7.82 change score on a scale Interval -9.32 to -6.32	-10.19 change score on a scale Interval -11.66 to -8.73

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: Only participants who completed the 6 months follow-up assessment were analyzed.

Treatment response defined as a ≥6 point reduction in Insomnia Severity Index score from baseline to follow-up. The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks. Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms. Data presented as count of participants meeting treatment response criteria at 6 months.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=38 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=32 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=34 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Number of Participants With Treatment Response of Insomnia Symptoms	22 Participants	21 Participants	31 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Only participants who completed the 6 months follow-up assessment were analyzed.

Remission of Insomnia symptoms defined as Insomnia Severity Index <8 at follow-up. The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks. Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms. Data presented as count of participants meeting insomnia remission criteria at 6 months.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=38 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=32 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=34 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Number of Participants With Remission of Insomnia Symptoms	16 Participants	13 Participants	16 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The Patient Health Questionnaire (PHQ-8) is an 8-item self-report measure for assessing depression severity. The items are summed to yield a score between 0 and 24, with higher scores indicating more frequent depression symptoms.

The Generalized Anxiety Disorder (GAD-7) Scale is a 7-item self-report measure used for screening and assessing severity of GAD. The items are summed to yield a score between 0 and 21, with higher scores indicating more severe GAD symptoms.

Change is estimated mean change in mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Anxiety and Depression Patient Health Questionnaire (PHQ-8)	-2.37 change score on a scale Interval -3.39 to -1.36	-2.74 change score on a scale Interval -3.87 to -1.61	-4.63 change score on a scale Interval -5.7 to -3.56
Change in Anxiety and Depression Generalized Anxiety Disorder (GAD-7)	-1.24 change score on a scale Interval -2.26 to -0.23	-2.16 change score on a scale Interval -3.29 to -1.03	-2.34 change score on a scale Interval -3.4 to -1.27

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The PROMIS Cognitive Function Short Form (8a) is an 8-item self-report measure related to executive functioning. Individual item responses range from 1 (very often) to 5 (never) and the total raw score is converted to standardized T-scores using established United States general adult population with a mean of 50 and a standard deviation of 10. Higher T-scores signify better cognitive function. Estimated mean change in T-score from baseline to follow-up is reported from mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site. Positive change indicates improved cognitive function.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Cognitive Function	2.87 T-score Interval 0.81 to 4.93	6.64 T-score Interval 4.36 to 8.93	4.58 T-score Interval 2.42 to 6.74

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The PROMIS Global Health is a 10-item self-report measure that assess general health and functioning. Item responses range from 1 (excellent/none) to 5 (poor/always) and a single pain item ranges from 0 (no pain) to 10 (worst pain). Physical and mental health sub-scores are calculated from 4 items each, and the total raw sub-scores (range: 4-20) are converted to T-scores using distributions standardized to mean 50 (SD 10) for the US general population. Higher score indicates greater health-related quality of life.

The Medical Outcome Survey (SF-12) is a 12-item self-report measure of physical and mental health. The Physical Component Score (PCS) and Mental Component Score (MCS) sub-scores range 0-100; higher score indicates better health.

Change is estimated mean change from baseline to follow-up in mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Patient-Reported Health Global Health: Mental	1.22 change score on a scale Interval -0.52 to 2.95	2.43 change score on a scale Interval 0.49 to 4.37	4.01 change score on a scale Interval 2.18 to 5.83
Change in Patient-Reported Health Global Health: Physical	2.87 change score on a scale Interval 1.22 to 4.52	2.51 change score on a scale Interval 0.68 to 4.35	3.59 change score on a scale Interval 1.86 to 5.32
Change in Patient-Reported Health SF-12 Physical Component Score	2.92 change score on a scale Interval 0.75 to 5.09	0.07 change score on a scale Interval -2.33 to 2.46	1.92 change score on a scale Interval -0.34 to 4.18
Change in Patient-Reported Health SF-12 Mental Component Score	-0.11 change score on a scale Interval -2.85 to 2.63	4.39 change score on a scale Interval 1.38 to 7.4	4.46 change score on a scale Interval 1.61 to 7.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The PROMIS Fatigue instrument is a 7-item self-report measure that assesses recent fatigue and how fatigue interfered with daily activities. Scores range from 7 to 35, with higher scores indicating greater fatigue.

Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Fatigue	-5.44 change score on a scale Interval -7.99 to -2.89	-8.82 change score on a scale Interval -11.66 to -5.99	-6.8 change score on a scale Interval -9.48 to -4.12

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The PROMIS Pain Intensity scale is a 3-item instrument used to assess how much pain a person has. Scores range from 3-15, with higher scores indicating greater pain intensity.

The PROMIS Pain Interference scale is a 6-item instrument used to assess the consequences of pain in different domains of daily life. Scores range from 6-30, with higher scores indicating greater interference.

Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Pain Intensity and Interference Pain Intensity	-0.55 change score on a scale Interval -2.7 to 1.6	-1.72 change score on a scale Interval -4.13 to 0.68	-3.84 change score on a scale Interval -6.11 to -1.58
Change in Pain Intensity and Interference Pain Interference	-1.81 change score on a scale Interval -4.26 to 0.63	0.72 change score on a scale Interval -2.01 to 3.44	-3.73 change score on a scale Interval -6.3 to -1.16

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The Pittsburgh Sleep Quality Index (PSQI) is an 18-item self-report measure that assesses sleep quality in the past month. These items are combined into seven component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction). The seven component scores are added to produce a global sleep quality score ranging from 0 to 21; higher total score indicates worse sleep quality.

Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Pittsburgh Sleep Quality Index	-3.42 change score on a scale Interval -4.46 to -2.38	-4.52 change score on a scale Interval -5.67 to -3.37	-5.23 change score on a scale Interval -6.32 to -4.15

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The Epworth Sleepiness Scale (ESS) is an 8-item self-report measure that assesses daytime sleepiness by asking about the likelihood of dozing in certain situations. Individual items are summed to yield the ESS score between 0 (never doze) to 24 (doze a lot) with higher scores indicating more sleepiness.

Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Daytime Sleepiness	-2.81 change score on a scale Interval -3.77 to -1.84	-2.61 change score on a scale Interval -3.68 to -1.54	-2.18 change score on a scale Interval -3.2 to -1.17

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

The Munich Chronotype Questionnaire (MCTQ) is a self-report scale to assess sleep structure, patterns, duration, and quality. The chronotype sub-score represents the mid-point time of sleep which is converted to a numeric value by adding the hour plus minutes divided by 60. Greater values indicate later chronotype. Positive change values indicate a shift to later chronotype.

Change is estimated mean change from mixed-effects linear regression model. Fixed effects: Treatment Arm, Visit and Treatment Arm*Visit interaction. Random effects: intercept for Subject, nested within Site.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Change in Munich Chronotype	0.08 hours Interval -0.16 to 0.33	-0.02 hours Interval -0.029 to 0.24	0.23 hours Interval -0.03 to 0.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

Population: 6 months mean only includes those who responded to the DBAS questions on the 6 month follow-up assessment.

Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale is a 16-item instrument used to evaluate dysfunctional thoughts related to insomnia. Each item is scored 0-10 and the total is the average of the 16 item scores (range 0-10), with higher scores indicating greater dysfunctional beliefs about sleep.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Dysfunctional Beliefs and Attitudes About Sleep Baseline DBAS mean total score	6.1 score on a scale Standard Deviation 1.8	6.0 score on a scale Standard Deviation 1.3	6.2 score on a scale Standard Deviation 1.7
Dysfunctional Beliefs and Attitudes About Sleep 6 months DBAS mean total score	5.4 score on a scale Standard Deviation 1.8	4.2 score on a scale Standard Deviation 1.6	4.0 score on a scale Standard Deviation 2.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 month, 9 weeks, 6 months

Population: Participants included if they completed the 1 month, 9 weeks or 6 month follow-up assessment.

Side effects (frequency, severity, impairment) are recorded via self-report adapted from the FIBSER. Scores range from 0 (no side effects; better) to 21 (worse). Side effects were analyzed if participant reported severity of greater than moderate and/or frequency greater than 50% of the time. Count of participants meeting the threshold for analysis up through the 6 month follow-up.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=45 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=40 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=41 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Number of Participants With Insomnia Treatment Side Effects	16 Participants	13 Participants	15 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 month, 9 weeks, 6 months, 9 months, 12 months

Population: Participants included if they completed the 1 month, 9 weeks, 6 month or 12 month follow-up assessment medications questions.

Medication use is assessed using self-reported prescription, over-the-counter, and supplement name and frequency. Count of participants reporting zolpidem or trazodone use for sleep is recorded for adherence to the Medication and Combination treatment arms.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=45 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=44 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Medication Adherence	38 Participants	28 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 month, 9 weeks, 6 months

Participants self-reported number of falls including context, location, and consequences of falls. Count of participants with one or more falls up through the 6 month follow-up.

Outcome measures

Measure	Medication (Zolpidem or Trazodone) n=49 Participants Zolpidem or trazodone, as prescribed by physician Zolpidem: Zolpidem, as prescribed by physician Trazodone: Trazodone, as prescribed by physician	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 Participants Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination n=52 Participants Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention Trazodone: Trazodone, as prescribed by physician
Self-reported Falls	8 Participants	3 Participants	7 Participants

Adverse Events

Medication (Zolpidem)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Medication (Trazodone)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Internet Cognitive Behavioral Therapy for Insomnia (CBT-I)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Combination (Zolpidem)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Combination (Trazodone)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Medication (Zolpidem) n=11 participants at risk Zolpidem: Zolpidem, as prescribed by physician Medication preference for zolpidem was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed zolpidem by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice.	Medication (Trazodone) n=38 participants at risk Trazodone: Trazodone, as prescribed by physician Medication preference for trazodone was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed trazodone by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice.	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 participants at risk Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination (Zolpidem) n=11 participants at risk Medication (zolpidem) and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Medication preference for zolpidem was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed zolpidem by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice. Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination (Trazodone) n=41 participants at risk Medication (trazodone) and Internet-based CBT-I program Trazodone: Trazodone, as prescribed by physician Medication preference for trazodone was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed trazodone by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice. Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention
Nervous system disorders Somnolence	0.00% 0/11 • 12 months	0.00% 0/38 • 12 months	1.9% 1/54 • Number of events 1 • 12 months	0.00% 0/11 • 12 months	0.00% 0/41 • 12 months
Infections and infestations Urinary tract infection	9.1% 1/11 • Number of events 1 • 12 months	0.00% 0/38 • 12 months	0.00% 0/54 • 12 months	0.00% 0/11 • 12 months	0.00% 0/41 • 12 months
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/11 • 12 months	0.00% 0/38 • 12 months	1.9% 1/54 • Number of events 1 • 12 months	0.00% 0/11 • 12 months	0.00% 0/41 • 12 months

Other adverse events

Measure	Medication (Zolpidem) n=11 participants at risk Zolpidem: Zolpidem, as prescribed by physician Medication preference for zolpidem was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed zolpidem by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice.	Medication (Trazodone) n=38 participants at risk Trazodone: Trazodone, as prescribed by physician Medication preference for trazodone was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed trazodone by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice.	Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) n=54 participants at risk Internet-based CBT-I program Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination (Zolpidem) n=11 participants at risk Medication (zolpidem) and Internet-based CBT-I program Zolpidem: Zolpidem, as prescribed by physician Medication preference for zolpidem was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed zolpidem by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice. Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention	Combination (Trazodone) n=41 participants at risk Medication (trazodone) and Internet-based CBT-I program Trazodone: Trazodone, as prescribed by physician Medication preference for trazodone was recorded prior to randomization by the provider and patient. Patients randomized to the medication arm were prescribed trazodone by their provider, guided by study-wide recommendations regarding initial doses and dose adjustments, however, prescribers were allowed to use clinical judgment reflecting their usual practice. Internet Cognitive Behavioral Therapy for Insomnia (CBT-I): 6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention
Cardiac disorders Palpatations	9.1% 1/11 • 12 months	0.00% 0/38 • 12 months	0.00% 0/54 • 12 months	0.00% 0/11 • 12 months	0.00% 0/41 • 12 months
Injury, poisoning and procedural complications Fall	9.1% 1/11 • 12 months	5.3% 2/38 • 12 months	3.7% 2/54 • 12 months	0.00% 0/11 • 12 months	9.8% 4/41 • 12 months
Musculoskeletal and connective tissue disorders Arthritis	9.1% 1/11 • 12 months	0.00% 0/38 • 12 months	0.00% 0/54 • 12 months	0.00% 0/11 • 12 months	0.00% 0/41 • 12 months
Nervous system disorders Dizziness	18.2% 2/11 • 12 months	0.00% 0/38 • 12 months	0.00% 0/54 • 12 months	0.00% 0/11 • 12 months	2.4% 1/41 • 12 months
Nervous system disorders Headache	9.1% 1/11 • 12 months	5.3% 2/38 • 12 months	0.00% 0/54 • 12 months	0.00% 0/11 • 12 months	2.4% 1/41 • 12 months
Nervous system disorders Somnolence	9.1% 1/11 • 12 months	15.8% 6/38 • 12 months	9.3% 5/54 • 12 months	18.2% 2/11 • 12 months	7.3% 3/41 • 12 months
Nervous system disorders Confusion	9.1% 1/11 • 12 months	0.00% 0/38 • 12 months	0.00% 0/54 • 12 months	0.00% 0/11 • 12 months	0.00% 0/41 • 12 months

Additional Information

Dr. Katie Stone

CPMCRI

Phone: (510) 427-4562

Email: katie.Stone@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place