Trial Outcomes & Findings for Effectiveness of Combining Behavioral and Pharmacologic Therapy for Complex Insomnia in Veterans With PTSD (NCT NCT03937713)
NCT ID: NCT03937713
Last Updated: 2025-10-21
Results Overview
The Pittsburgh Sleep Quality Index is a 19-item, self-rated questionnaire, assessed various aspects of sleep, sleep quality, and sleep disturbances. The PSQI is composed of 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score. An overall score ranges from 0 to 21, where lower scores denote a healthier sleep quality.
COMPLETED
PHASE4
53 participants
repeated measures between baseline and 6 months post randomization
2025-10-21
Participant Flow
During the period extending from January 4th, 2020, and December 28th, 2023, we assessed 425 veterans with PTSD for eligibility.
Three hundred sixty-three Veterans were excluded because of prior treatment with CBT-I and/or active use of hypnotics (81%), presence of concurrent active medical or unstable psychiatric conditions (5%), active substance abuse (1%), documented sleep disorders other than COMISA (4%), or unable to commit for the duration of the trial (9%). Of the 62 veterans who met eligibility, nine did not meet the criteria for clinical insomnia by ISI.
Participant milestones
| Measure |
BBTI Plus Eszopiclone
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
27
|
|
Overall Study
End of Treatment
|
24
|
23
|
|
Overall Study
End of Study
|
22
|
21
|
|
Overall Study
COMPLETED
|
22
|
21
|
|
Overall Study
NOT COMPLETED
|
4
|
6
|
Reasons for withdrawal
| Measure |
BBTI Plus Eszopiclone
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
6
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Effectiveness of Combining Behavioral and Pharmacologic Therapy for Complex Insomnia in Veterans With PTSD
Baseline characteristics by cohort
| Measure |
BBTI Plus Eszopiclone
n=26 Participants
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 Participants
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
Total
n=53 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48.0 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
48.4 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
48.2 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=5 Participants
|
27 participants
n=7 Participants
|
53 participants
n=5 Participants
|
|
BMI
|
32.8 kg.m(-2)
STANDARD_DEVIATION 6.8 • n=5 Participants
|
33.0 kg.m(-2)
STANDARD_DEVIATION 6.6 • n=7 Participants
|
32.9 kg.m(-2)
STANDARD_DEVIATION 6.7 • n=5 Participants
|
|
Pittsburgh Sleep Quality Index (PSQI)
|
13.0 units on a scale
STANDARD_DEVIATION 3.4 • n=5 Participants
|
13.7 units on a scale
STANDARD_DEVIATION 2.7 • n=7 Participants
|
13.4 units on a scale
STANDARD_DEVIATION 3.1 • n=5 Participants
|
|
PTSD checklist-5 (PCL-5)
|
34.5 units on a scale
STANDARD_DEVIATION 11.5 • n=5 Participants
|
30.1 units on a scale
STANDARD_DEVIATION 12.8 • n=7 Participants
|
32.2 units on a scale
STANDARD_DEVIATION 12.2 • n=5 Participants
|
|
Apnea-Hypopnea Index (AHI)
|
29.2 events per hour
STANDARD_DEVIATION 22.9 • n=5 Participants
|
32.7 events per hour
STANDARD_DEVIATION 25.3 • n=7 Participants
|
31.0 events per hour
STANDARD_DEVIATION 24.1 • n=5 Participants
|
|
Beck Depression Inventory (BDI)
|
15.7 units on a scale
STANDARD_DEVIATION 8.5 • n=5 Participants
|
16.1 units on a scale
STANDARD_DEVIATION 13.1 • n=7 Participants
|
15.9 units on a scale
STANDARD_DEVIATION 11.1 • n=5 Participants
|
|
Insomnia Severity Index (ISI)
|
18.2 units on a scale
STANDARD_DEVIATION 4.3 • n=5 Participants
|
18.7 units on a scale
STANDARD_DEVIATION 4.1 • n=7 Participants
|
18.3 units on a scale
STANDARD_DEVIATION 4.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: repeated measures between baseline and 6 months post randomizationPopulation: All analyses were based on the intention-to-treat principle
The Pittsburgh Sleep Quality Index is a 19-item, self-rated questionnaire, assessed various aspects of sleep, sleep quality, and sleep disturbances. The PSQI is composed of 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score. An overall score ranges from 0 to 21, where lower scores denote a healthier sleep quality.
Outcome measures
| Measure |
BBTI Plus Eszopiclone
n=26 Participants
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 Participants
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Change in Pittsburgh Sleep Quality Index (PSQI) (32) at 6 Months Post-randomization
|
-5.25 units on a scale
Interval -6.58 to -3.91
|
-5.45 units on a scale
Interval -6.78 to -4.11
|
SECONDARY outcome
Timeframe: repeated measures between baseline and 6 months post randomizationPopulation: All analyses were based on the intention-to-treat principle
PCL-5 is a 20-item self-report measures that have been widely used in military and civilian population to assess the severity of PTSD symptoms. A total symptom severity score (range 0-80) can be obtained by summing the scores from each of the 20 items that have response options from 0 "not at all" to 4 "extremely". Higher score indicates worse symptoms.
Outcome measures
| Measure |
BBTI Plus Eszopiclone
n=26 Participants
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 Participants
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Change in PTSD Checklist-5 (PCL-5)
|
-10.63 units on a scale
Interval -15.09 to -6.17
|
-4.46 units on a scale
Interval -8.9 to 0.01
|
SECONDARY outcome
Timeframe: repeated measures between baseline and 6 months post randomizationPopulation: All analyses were based on the intention-to-treat principle
The ISI is a 7-item patient-reported outcome assessing the severity of initial, middle, and late insomnia; sleep satisfaction; interference of insomnia with daytime functioning; noticeability of sleep problems by others; and distress about sleep difficulties. The 5 point scale provides a score ranging from 0 to 28 with higher scores indicating more severe insomnia.
Outcome measures
| Measure |
BBTI Plus Eszopiclone
n=26 Participants
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 Participants
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Change in Insomnia Severity Index (ISI)
|
-8.32 units on a scale
Interval -10.56 to -6.09
|
-8.64 units on a scale
Interval -10.92 to -6.36
|
SECONDARY outcome
Timeframe: repeated measures between baseline and 6 months post randomizationPopulation: All analyses were based on the intention-to-treat principle
The BDI-II is a 21-item questionnaire in which respondents indicate on a four-point Likert-type scale (0=minimal to 3=severe) the presence and severity of depressive symptoms during the past 2 weeks. Items are scored on a 4-point scale ranging from 0 to 3, with higher scores indicating the presence of more depressive symptoms. The BDI-score ranges from 0 to 63. Higher scores indicate worse outcomes.
Outcome measures
| Measure |
BBTI Plus Eszopiclone
n=26 Participants
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 Participants
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Change in Beck Depression Inventory-II (BDI-II)
|
-4.34 units on a scale
Interval -7.04 to -1.63
|
-3.07 units on a scale
Interval -5.76 to -0.37
|
OTHER_PRE_SPECIFIED outcome
Timeframe: repeated measures between baseline and 6 months post randomizationPopulation: All analyses were based on the intention-to-treat principle
CPAP adherence will be obtained by downloading the data stored on the SmartCard. CPAP adherence is defined as the use of CPAP for 4 hours or more per night during a 28 consecutive day period. The outcome measure is the percentage of patients who met the definition of CPAP adherence based on the last 28 days prior to the 6 month time point.
Outcome measures
| Measure |
BBTI Plus Eszopiclone
n=26 Participants
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 Participants
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
CPAP Adherence
|
37.15 percentage of participants
|
16.85 percentage of participants
|
Adverse Events
BBTI Plus Eszopiclone
BBTI
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BBTI Plus Eszopiclone
n=26 participants at risk
participants randomized to the combination therapy will receive eszopiclone 2 mg orally at bedtime or placebo starting with the BBTI sessions for a period of 2 weeks in combination with 4 sessions of BBTI over 4 weeks.
eszopiclone: Eszopiclone is a nonbenzodiazepine benzodiazepine receptor agonists, effective for both sleep onset insomnia and sleep maintenance insomnia
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
BBTI
n=27 participants at risk
participants randomized to BBTI will receive 4 sessions of BBTI over 4 weeks.
Brief behavioral therapy for insomnia: BBTI is based on the core principles that are fundamental to other empirically-supported behavioral treatments of insomnia delivered over four consecutive weeks.
|
|---|---|---|
|
Nervous system disorders
Headache
|
7.7%
2/26 • Number of events 2 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
Nervous system disorders
Diziness
|
7.7%
2/26 • Number of events 2 • 6 months
|
0.00%
0/27 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place