Chronic Insomnia, Posttraumatic Stress Disorders
Conditions
Keywords
PTSD, insomnia, CBT-I, Prolonged Exposure, Veteran
Brief summary
This study aims to examine whether integrating insomnia and PTSD treatment will enhance sleep, PTSD, and quality of life outcomes. This is a randomized control trial comparing integrated evidence based CBT-I into PE (CBTI-PE) versus to a non-active sleep component plus PE (hygiene-PE) to optimize PTSD, sleep, and quality of life outcomes in 90 Veterans. Such benefits would further the VA's commitment to improving the mental health, recovery, and community reintegration of Veterans detailed in the 2014-2020 VHA Strategic Plan. Findings from the proposed study offer a unique opportunity to determine the malleability of mechanisms (e.g., Total sleep time, Sleep efficiency) that can improve recovery outcomes among this vulnerable population and to inform future treatment development and research. Improved PTSD, insomnia, and quality of life outcomes can decrease risk of chronic impairment and ultimately help affected Veterans live richer, more productive lives.
Detailed description
The lifetime prevalence of posttraumatic stress disorder (PTSD) is approximately 30% among Vietnam Veterans and 11-17% among Iraq and Afghanistan Veterans. PTSD is associated with enormous health care costs, increased suicidality, depression, poorer quality of life and functioning, physical health, and increased substance use. Prolonged exposure (PE) is an efficacious treatment for Veterans with PTSD that decreases avoidance of feared, but safe, cues. Despite PE being one of the best available treatments for PTSD, 25 to 45% of PTSD patients still meet diagnostic criteria following treatment. High rates of comorbid disorders, such as insomnia, may interfere with the efficacy of PE and limit long-term rehabilitation outcomes. Among Veterans with PTSD, sleep disturbances are nearly universal with 70 - 87% reporting comorbid insomnia. Untreated insomnia can persist for years, is independently associated with impaired health-related quality of life, does not resolve following PTSD treatment, and can exacerbate daytime PTSD symptoms. Importantly, insomnia may interfere with the mechanisms of PE through safety learning, habituation to feared stimuli, emotional coping, emotional processing, and cognitive abilities necessary for successful treatment. Despite this, insomnia is not a primary intervention for Veterans with PTSD. Given these factors, it is critical to evaluate whether treating insomnia prior to PTSD will improve PTSD symptoms and quality of life outcomes. Cognitive behavioral treatment for insomnia (CBT-I) is the first line treatment of chronic and severe insomnia, which produces lasting improvements in sleep. By using CBT-I prior to, and integrated with, PE offers several novel advantages that will: 1) increase client-centered treatment by addressing the number one subjective complaint among Veterans with PTSD; 2) enhance PTSD outcomes and non-response rates by addressing insomnia-related factors that interfere with PTSD treatment; 3) act as a stepping stone and help to engage patients who are not initially willing to engage in trauma-focused PE; 4) increase rehabilitation outcomes by addressing the two leading disorders that independently affect quality of life for Veterans; 5) allow patients to address both symptoms of insomnia and PTSD within a shortened timeframe; 6) increase continuity by allowing patients to work with a single provider; and 7) decrease the risk of attrition between referral clinics and waitlists. To date, no studies have capitalized on available evidence-based CBT-I prior to PE to improve insomnia, PTSD, and quality of life outcomes.
Interventions
BEHAVIORALCBTI-PE
Integrates CBT-I and PE with the goal of enhancing both insomnia and PTSD outcomes. Integrated treatment will be delivered in 14 90-minute weekly sessions. CBTI-PE starts with VA rollout CBT-I for the first 3 weeks with a focus on the effects of PTSD on insomnia. PE protocol (psychoeducation) begins on week 4 of treatment and both treatments overlap till week 6 when CBT-I ends and the active treatment of PE begins (i.e., imaginal and in-vivo exposures). However, CBT-I sleep diary review and sleep time adjustment will continue till the end of treatment to increase adherence
BEHAVIORALHygiene-PE
The investigators have included a non-active sleep control arm (3 Sessions)to allow for the dose response of 14 90 minute sessions. The non-active sleep control condition used in this study is a manualized protocol developed to exclude the active components of standard CBT-I treatment. Hygiene includes presentation of sleep hygiene education and reviewing daily stressors that may impact sleep before starting PE on week 4.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Over the age of 19 years old * Diagnosis of PTSD * Meet diagnostic criteria for insomnia * Enrolled at the VA San Diego Healthcare System (VASDHS) and living within 50 miles of the respective facility * English literacy
Exclusion criteria
* Unmanaged psychosis or manic episodes in past year * Substance/alcohol use disorder in past 6 months * Diagnosed (previously or by the investigators' study screen) and untreated sleep disorder other than insomnia * Sleep disorders diagnosed, but stably treated, such as obstructive sleep apnea treated with continuous positive airway pressure (CPAP), will be allowed) * Participation in concurrent psychotherapies targeting PTSD * Veteran can be reassessed after their PTSD treatment concludes * Veterans who are engaged in treatment for non-PTSD symptoms (e.g., 12-step programs) will be eligible * Severe medical or psychiatric illness that would make it difficult to regularly attend psychotherapy sessions or participate fully in the study * History of moderate to severe cognitive impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PTSD Symptoms | Baseline, Post Treatment (14-weeks), Follow-up (26-weeks) | PTSD Symptoms will be assessed using the Clinician-Administered PTSD Scale DSM 5 (CAPS-5). Range (0 - 80). Lower scores equate to lower PTSD severity. Change in PTSD will be assessed longitudinally using linear mixed effects models of the CAPS-5 at each timepoint to estimate slope (change) over time. |
| Change in Sleep Efficiency | Baseline, Post Treatment (14-weeks), Follow-up (26-weeks) | Change in sleep efficiency. Sleep efficiency is calculated from two variables acquired from daily sleep logs filled out by patient: a) time spend in bed and b) time spent asleep. Sleep efficiency = time spent asleep / time spent in bed. Range (0 -100%). Higher sleep efficiency is better. Change in Sleep Efficiency will be assessed longitudinally using linear mixed effects models of measure at each timepoint to estimate slope (change) over time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life | Baseline, Post Treatment (14-weeks), Follow-up (26-weeks) | Change in Quality of life will be assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. All subscores, higher scores equate to better quality of life. Physical Health Range (7-35); Psychological Range (6-30); Social Relationships (3-15); Environment (8-40). |
| Change in Insomnia Severity | Baseline, week 5, Post Treatment (14-weeks), Follow-up (26-weeks) | Insomnia Severity will be assessed using the Insomnia Severity Index (ISI). Range (0 - 28). Lower scores equate to lower insomnia severity. Change in ISI will be assessed longitudinally using linear mixed effects models of the ISI scores at each timepoint to estimate slope (change) over time. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Client Satisfaction Questionnaire (CSQ) | Post Treatment ( up to 14-weeks) | CSQ assesses client satisfaction for therapy session. Range (8-32) with higher scores equating to higher satisfaction. |
| Brief Pain Inventory | post treatment, and 3-month follow-ups presented. | Brief Pain Inventory ranges from 0 - 40, with higher score indicating worse pain. |
Countries
United States
Participant flow
Pre-assignment details
94 participants met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| CBTI-PE Integrates the core components of CBT-I and PE in 14 90-minute weekly sessions.
CBTI-PE: Integrates CBT-I and PE with the goal of enhancing both insomnia and PTSD outcomes. Integrated treatment will be delivered in 14 90-minute weekly sessions. CBTI-PE starts with VA rollout CBT-I for the first 3 weeks with a focus on the effects of PTSD on insomnia. PE protocol (psychoeducation) begins on week 4 of treatment and both treatments overlap till week 6 when CBT-I ends and the active treatment of PE begins (i.e., imaginal and in-vivo exposures). However, CBT-I sleep diary review and sleep time adjustment will continue till the end of treatment to increase adherence | 52 |
| Hygiene-PE Uses non-active sleep hygiene to account for the dose response of experimental condition before starting PE. Uses 14 90-minute weekly sessions.
Hygiene-PE: The investigators have included a non-active sleep control arm (3 Sessions)to allow for the dose response of 14 90 minute sessions. The non-active sleep control condition used in this study is a manualized protocol developed to exclude the active components of standard CBT-I treatment. Hygiene includes presentation of sleep hygiene education and reviewing daily stressors that may impact sleep before starting PE on week 4. | 42 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 9 | 7 |
Baseline characteristics
| Characteristic | Hygiene-PE | Total | CBTI-PE |
|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 12.4 | 40.2 years STANDARD_DEVIATION 11.8 | 39.4 years STANDARD_DEVIATION 11.3 |
| Clinician Administered PTSD Scale (CAPS) | 37 units on a scale STANDARD_DEVIATION 9.5 | 38 units on a scale STANDARD_DEVIATION 8.1 | 38.6 units on a scale STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 29 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 63 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Insomnia Severity Index | 19.67 units on a scale STANDARD_DEVIATION 4.63 | 20.53 units on a scale STANDARD_DEVIATION 4.73 | 21.26 units on a scale STANDARD_DEVIATION 4.7 |
| Quality of Life Environment | 13.64 units on a scale STANDARD_DEVIATION 2.67 | 12.85 units on a scale STANDARD_DEVIATION 3.09 | 12.20 units on a scale STANDARD_DEVIATION 3.27 |
| Quality of Life Physical Health | 11.34 units on a scale STANDARD_DEVIATION 2.09 | 10.26 units on a scale STANDARD_DEVIATION 2.62 | 9.38 units on a scale STANDARD_DEVIATION 2.7 |
| Quality of Life Psychological | 11.19 units on a scale STANDARD_DEVIATION 2.73 | 10.16 units on a scale STANDARD_DEVIATION 3.16 | 9.33 units on a scale STANDARD_DEVIATION 3.28 |
| Quality of Life Social relationships | 11.19 units on a scale STANDARD_DEVIATION 3.78 | 10.26 units on a scale STANDARD_DEVIATION 4 | 9.51 units on a scale STANDARD_DEVIATION 4.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 17 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 49 Participants | 26 Participants |
| Region of Enrollment United States | 42 Participants | 94 Participants | 52 Participants |
| Sex: Female, Male Female | 10 Participants | 22 Participants | 12 Participants |
| Sex: Female, Male Male | 32 Participants | 72 Participants | 40 Participants |
| Sleep Efficiency (SE) | 74.87 Percentage of time asleep time in bed STANDARD_DEVIATION 10.9 | 72.45 Percentage of time asleep time in bed STANDARD_DEVIATION 13.28 | 70.94 Percentage of time asleep time in bed STANDARD_DEVIATION 14.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 35 |
| other Total, other adverse events | 0 / 43 | 0 / 35 |
| serious Total, serious adverse events | 1 / 43 | 0 / 35 |
Outcome results
Primary
Change in PTSD Symptoms
PTSD Symptoms will be assessed using the Clinician-Administered PTSD Scale DSM 5 (CAPS-5). Range (0 - 80). Lower scores equate to lower PTSD severity. Change in PTSD will be assessed longitudinally using linear mixed effects models of the CAPS-5 at each timepoint to estimate slope (change) over time.
Time frame: Baseline, Post Treatment (14-weeks), Follow-up (26-weeks)
Population: Individuals who gave at least 2 time points are included in ITT analyses in the estimation models. Observed means at each timepoint are presented below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CBTI-PE | Change in PTSD Symptoms | Post-Treatment | 25.74 score on a scale | Standard Error 12.34 |
| CBTI-PE | Change in PTSD Symptoms | 3 Month Follow-up | 28.59 score on a scale | Standard Error 12.68 |
| Hygiene-PE | Change in PTSD Symptoms | Post-Treatment | 28.18 score on a scale | Standard Error 11.62 |
| Hygiene-PE | Change in PTSD Symptoms | 3 Month Follow-up | 24.93 score on a scale | Standard Error 12.61 |
Primary
Change in Sleep Efficiency
Change in sleep efficiency. Sleep efficiency is calculated from two variables acquired from daily sleep logs filled out by patient: a) time spend in bed and b) time spent asleep. Sleep efficiency = time spent asleep / time spent in bed. Range (0 -100%). Higher sleep efficiency is better. Change in Sleep Efficiency will be assessed longitudinally using linear mixed effects models of measure at each timepoint to estimate slope (change) over time.
Time frame: Baseline, Post Treatment (14-weeks), Follow-up (26-weeks)
Population: Individuals who gave at least 2 time points are included in ITT analyses in the estimation models. Observed means at each timepoint are presented below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CBTI-PE | Change in Sleep Efficiency | 3 Month Follow-Up | 86.46 Percentage of time asleep time in bed | Standard Deviation 7.67 |
| CBTI-PE | Change in Sleep Efficiency | Post-Treatment | 88.71 Percentage of time asleep time in bed | Standard Deviation 6.46 |
| Hygiene-PE | Change in Sleep Efficiency | Post-Treatment | 78.44 Percentage of time asleep time in bed | Standard Deviation 9.71 |
| Hygiene-PE | Change in Sleep Efficiency | 3 Month Follow-Up | 78.23 Percentage of time asleep time in bed | Standard Deviation 10.86 |
Secondary
Change in Insomnia Severity
Insomnia Severity will be assessed using the Insomnia Severity Index (ISI). Range (0 - 28). Lower scores equate to lower insomnia severity. Change in ISI will be assessed longitudinally using linear mixed effects models of the ISI scores at each timepoint to estimate slope (change) over time.
Time frame: Baseline, week 5, Post Treatment (14-weeks), Follow-up (26-weeks)
Population: Individuals who gave at least 2 time points are included in ITT analyses in the estimation models. Observed means at each timepoint are presented below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CBTI-PE | Change in Insomnia Severity | Post-Treatment | 9.46 score on a scale | Standard Error 6.98 |
| CBTI-PE | Change in Insomnia Severity | 3 Month Follow-up | 11.76 score on a scale | Standard Error 6.7 |
| CBTI-PE | Change in Insomnia Severity | Week 5 | 15.13 score on a scale | Standard Error 6.5 |
| Hygiene-PE | Change in Insomnia Severity | Post-Treatment | 12.93 score on a scale | Standard Error 6.58 |
| Hygiene-PE | Change in Insomnia Severity | Week 5 | 17.69 score on a scale | Standard Error 4.76 |
| Hygiene-PE | Change in Insomnia Severity | 3 Month Follow-up | 12.37 score on a scale | Standard Error 7.57 |
Secondary
Change in Quality of Life
Change in Quality of life will be assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. All subscores, higher scores equate to better quality of life. Physical Health Range (7-35); Psychological Range (6-30); Social Relationships (3-15); Environment (8-40).
Time frame: Baseline, Post Treatment (14-weeks), Follow-up (26-weeks)
Population: Participants analyzed are the observed means. Different from the Intent to treat number of participants reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CBTI-PE | Change in Quality of Life | Physical Health - Post TX | 11.6 score on a scale | Standard Deviation 5.32 |
| CBTI-PE | Change in Quality of Life | Physical Health - 3m | 10.12 score on a scale | Standard Deviation 6.14 |
| CBTI-PE | Change in Quality of Life | Psychological - post treatment | 10.46 score on a scale | Standard Deviation 4.81 |
| CBTI-PE | Change in Quality of Life | Psychological - 3m | 9.31 score on a scale | Standard Deviation 5.77 |
| CBTI-PE | Change in Quality of Life | Social relationships - post-TX | 10.63 score on a scale | Standard Deviation 5.05 |
| CBTI-PE | Change in Quality of Life | Social relationships - 3m | 9.61 score on a scale | Standard Deviation 6.46 |
| CBTI-PE | Change in Quality of Life | Environment - post-tx | 12.13 score on a scale | Standard Deviation 5.22 |
| CBTI-PE | Change in Quality of Life | Environment - 3m | 11.15 score on a scale | Standard Deviation 6.56 |
| Hygiene-PE | Change in Quality of Life | Environment - 3m | 12.94 score on a scale | Standard Deviation 5.31 |
| Hygiene-PE | Change in Quality of Life | Physical Health - Post TX | 10.53 score on a scale | Standard Deviation 6.44 |
| Hygiene-PE | Change in Quality of Life | Social relationships - post-TX | 9.49 score on a scale | Standard Deviation 5.98 |
| Hygiene-PE | Change in Quality of Life | Physical Health - 3m | 12.11 score on a scale | Standard Deviation 7.56 |
| Hygiene-PE | Change in Quality of Life | Environment - post-tx | 11.08 score on a scale | Standard Deviation 6.34 |
| Hygiene-PE | Change in Quality of Life | Psychological - post treatment | 10.26 score on a scale | Standard Deviation 6.13 |
| Hygiene-PE | Change in Quality of Life | Social relationships - 3m | 11.24 score on a scale | Standard Deviation 4.99 |
| Hygiene-PE | Change in Quality of Life | Psychological - 3m | 11.64 score on a scale | Standard Deviation 4.99 |
Other Pre-specified
Brief Pain Inventory
Brief Pain Inventory ranges from 0 - 40, with higher score indicating worse pain.
Time frame: post treatment, and 3-month follow-ups presented.
Population: N is for observed means only, not Intent to Treatment repeated measures analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CBTI-PE | Brief Pain Inventory | Post-Treatment | 18.69 score on a scale | Standard Deviation 9.14 |
| CBTI-PE | Brief Pain Inventory | 3 Month Follow-up | 18.41 score on a scale | Standard Deviation 7.81 |
| Hygiene-PE | Brief Pain Inventory | Post-Treatment | 15.63 score on a scale | Standard Deviation 10.12 |
| Hygiene-PE | Brief Pain Inventory | 3 Month Follow-up | 16.08 score on a scale | Standard Deviation 9.94 |
Other Pre-specified
The Client Satisfaction Questionnaire (CSQ)
CSQ assesses client satisfaction for therapy session. Range (8-32) with higher scores equating to higher satisfaction.
Time frame: Post Treatment ( up to 14-weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBTI-PE | The Client Satisfaction Questionnaire (CSQ) | 29.41 score on a scale | Standard Deviation 3.11 |
| Hygiene-PE | The Client Satisfaction Questionnaire (CSQ) | 29.56 score on a scale | Standard Deviation 2.97 |