PTSD, Sleep Disorders
Conditions
Keywords
Combat Trauma, Post traumatic stress disorder, PTSD, Sleep Disturbance, Trauma-Related Nightmares
Brief summary
Background: Posttraumatic stress disorder (PTSD) is a debilitating and disabling mental disorder that afflicts at least 25% of Veterans who have suffered life-threatening war zone trauma. Trauma-related nightmares and sleep disturbance are among the most treatment-resistant PTSD symptoms in Veterans. Increased responsiveness to central nervous system (CNS) norepinephrine (NE) contributes to the pathophysiology of overall PTSD and treatment-resistant nighttime symptoms. Placebo-controlled pilot studies demonstrate that the generically available CNS-active alpha-1 adrenoreceptor antagonist prazosin substantially reduces PTSD trauma nightmares and sleep disturbance and improves global clinical status (sense of well being and ability to function) in Veterans. Objective: The primary objective is to demonstrate in a large multi-site placebo-controlled trial in Veterans with war zone trauma-induced PTSD that prazosin is efficacious for PTSD trauma nightmares, sleep disturbance, and global clinical status. A secondary objective is to demonstrate prazosin effectiveness for these outcome measures during clinically meaningful long-term (26 week) maintenance treatment of PTSD. The investigators will also address prazosin efficacy and long-term effectiveness for improving total PTSD symptoms, comorbid depression, quality of life, and physical functioning. Methods: This 26 week randomized double-blind placebo-controlled study is designed to demonstrate both short term efficacy and long term effectiveness of prazosin for PTSD. The research design encompasses a shorter-term, more tightly controlled efficacy component and a longer-term, more .real world. effectiveness component. Three hundred twenty-six Veterans with war zone -related PTSD and persistent trauma nightmares will be randomized 1:1 to prazosin or placebo. Study drug will be increased using a flexible dose titration schedule based on clinical response and adverse effects to an optimum maintenance dose (1-20 mg/day). During the first 10 weeks of the study, participants will be randomized to prazosin or placebo. Previous psychotropic medications and/or psychotherapy will be maintained constant. Short term efficacy will be determined during the first 10 weeks. During the remaining 16 weeks of the 26 week trial, subjects will continue to receive stable-dose double-blind prazosin or placebo, but will have the option to receive additional psychotropic medications and/or psychotherapeutic interventions, as needed, per the judgment of the study Clinician Prescriber. It is hypothesized that prazosin will remain more clinically effective than placebo at the end of the 26-week trial, demonstrating that prazosin adds benefit over-and-above other treatments that are naturalistically administered by providers in a .real world. clinical setting. Prazosin will be judged efficacious at 10 weeks if superior to placebo on all three primary outcome measures assessing trauma nightmares, sleep disturbance, and global clinical status: the Recurrent Distressing Dreams item of the Clinician Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression of Change (CGIC). Secondary outcome measures will assess prazosin effects on total PTSD symptoms, depression, physical functioning, and quality of life. Adverse effects and cardiovascular measures, including supine and standing blood pressure (BP) and heart rate (HR) will be assessed.
Interventions
DRUGprazosin
Subjects will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized first dose effect of prazosin or any alpha-1 antagonist if started at a high dose. As a further precaution, male subjects will be advised to sit on the toilet for urination at night during the first week of dose titration. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) and then titrating the dose upward gradually.
OTHERplacebo
sugar pill
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age \>18 years. * Exposure to one or more life-threatening war zone trauma events per the Combat * Exposure Scale \[78\] and documented by Department of Defense (DD) Form 214, Combat Action Ribbon (Marines), Combat Infantry Badge (Army), or other clear evidence of war zone trauma exposure. * Eligible for VA health care. * Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of PTSD derived from the CAPS. * CAPS total score \>50. * CAPS Recurrent Distressing Dreams item score \>5 (of maximum score of 8). * Capable of giving informed consent. * Stable dose of non-exclusionary (see below) medications for at least 4 weeks prior to randomization. * Psychotherapeutic treatment stable for at least 4 weeks prior to randomization. * Good general medical health (see Medical
Exclusion criteria
below). * Female participants must agree to use a reliable form of birth control during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CAPS Recurrent Distressing Dreams Item | This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported. | Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms. |
| Pittsburgh Sleep Quality Index (PSQI) | This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported. | Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep. |
| Clinical Global Impression of Change (CGIC) | This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported. | Change from baseline in possible range for Clinical Global Impression of Change 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total CAPS Score | The total CAPS was administered at baseline, 6, 10, 18, and 26 weeks (or early termination). | Change from baseline in possible range for CAPS total score is 0-136. Higher score indicates more severe PTSD symptoms. |
| PTSD Checklist-Military Version (PCL-M) Score | This secondary outcome was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks to assess change in PTSD symptom severity. | Change from baseline in possible range for PCL-M score 17-85. Higher PCL score indicates greater propensity for chronic and delayed PTSD. |
| Patient Health Questionnaire-9 (PHQ9) | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for PHQ9 score is 0-27. Higher PHQ9 score indicates more severe depression. |
| Pittsburgh Sleep Quality Index | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep. |
| SF-12 Mental Standardized Score (SF-12 MCS) | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for SF-12 MCS is 5-76. Higher SF-12 score indicates better level of health. |
| Quality of Life Inventory (QOLI) | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for QOLI is -6 to 6. Higher QOLI indicates better satisfaction with life. |
| Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for Audit-C score is 0-12. Higher score indicates heavier use of alcohol. A score of \>=4 for male and a score of \>=3 for female meets the criteria for alcohol use disorders. |
| SF-12 Physical Standardized Score (SF-12 PCS) | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for SF-12 PCS is 6-72. Higher SF-12 score indicates better level of health. |
| CAPS Recurrent Distressing Dreams Item | This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination) to assess temporal course of changes in symptoms in response to prazosin or placebo. | Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms. |
| Clinical Global Impression of Change | This secondary outcome measure was administered at 6, 10, 14, 18, 22 and 26 weeks (or early termination). | Change from baseline in possible range for Clinical Global Impression of Change (CGIC) 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prazosin Group Subjects randomized to this arm will be on prazosin.
prazosin: Subjects will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized first dose effect of prazosin or any alpha-1 antagonist if started at a high dose. As a further precaution, male subjects will be advised to sit on the toilet for urination at night during the first week of dose titration. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) and then titrating the dose upward gradually. | 152 |
| Placebo Group Subjects randomized to this arm will be on placebo.
placebo: sugar pill | 152 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 |
| Overall Study | Contraindicative Medication | 1 | 0 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 10 | 7 |
| Overall Study | Physician Decision | 1 | 6 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Subject Moved Away | 3 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 9 |
Baseline characteristics
| Characteristic | Total | Prazosin Group | Placebo Group |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 13.8 | 52.3 years STANDARD_DEVIATION 13.8 | 51.4 years STANDARD_DEVIATION 13.8 |
| Highest Educational Level College Graduate | 47 participants | 22 participants | 25 participants |
| Highest Educational Level Did Not Answer | 4 participants | 2 participants | 2 participants |
| Highest Educational Level Grade School or Less | 0 participants | 0 participants | 0 participants |
| Highest Educational Level High School/GED | 64 participants | 35 participants | 29 participants |
| Highest Educational Level Other | 3 participants | 2 participants | 1 participants |
| Highest Educational Level Post Graduate/Professional Degree | 20 participants | 7 participants | 13 participants |
| Highest Educational Level Some College/Ass.Degree/Tech.School | 156 participants | 79 participants | 77 participants |
| Highest Educational Level Some High School | 10 participants | 5 participants | 5 participants |
| Maintained on any Antidepressant No | 68 participants | 33 participants | 35 participants |
| Maintained on any Antidepressant Yes | 236 participants | 119 participants | 117 participants |
| Maintained on Selective Serotonin Re-uptake Inhibitors (SSRI) No | 78 participants | 39 participants | 39 participants |
| Maintained on Selective Serotonin Re-uptake Inhibitors (SSRI) Yes | 226 participants | 113 participants | 113 participants |
| Major Depression No | 189 participants | 101 participants | 88 participants |
| Major Depression Yes | 115 participants | 51 participants | 64 participants |
| Marital Status Did Not Answer | 4 participants | 2 participants | 2 participants |
| Marital Status Divorced | 66 participants | 39 participants | 27 participants |
| Marital Status Living Together in a Relationship | 7 participants | 3 participants | 4 participants |
| Marital Status Married | 171 participants | 82 participants | 89 participants |
| Marital Status Separated | 12 participants | 6 participants | 6 participants |
| Marital Status Single | 37 participants | 17 participants | 20 participants |
| Marital Status Widowed | 7 participants | 3 participants | 4 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 75 Participants | 38 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 13 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 8 Participants | 8 Participants |
| Race (NIH/OMB) White | 192 Participants | 91 Participants | 101 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 297 Participants | 146 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 142 / 152 | 139 / 152 |
| serious Total, serious adverse events | 18 / 152 | 17 / 152 |
Outcome results
Primary
CAPS Recurrent Distressing Dreams Item
Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms.
Time frame: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.
Population: 17 participants in the prazosin group have missing data on this item at week 10; 16 participants in the placebo group have missing data on this item at week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | -1.9 scores on a scale | Standard Deviation 2.1 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | -1.7 scores on a scale | Standard Deviation 2.3 |
Primary
Clinical Global Impression of Change (CGIC)
Change from baseline in possible range for Clinical Global Impression of Change 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening.
Time frame: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.
Population: 17 participants in the prazosin group have missing data on this item at week 10; 16 participants in the placebo group have missing data on this item at week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin Group | Clinical Global Impression of Change (CGIC) | 3.3 scores on a scale | Standard Deviation 1.4 |
| Placebo Group | Clinical Global Impression of Change (CGIC) | 3.3 scores on a scale | Standard Deviation 1.4 |
Primary
Pittsburgh Sleep Quality Index (PSQI)
Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep.
Time frame: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.
Population: 17 participants in the prazosin group have missing data on this item at week 10; 16 participants in the placebo group have missing data on this item at week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin Group | Pittsburgh Sleep Quality Index (PSQI) | -2.3 scores on a scale | Standard Deviation 4.2 |
| Placebo Group | Pittsburgh Sleep Quality Index (PSQI) | -2.1 scores on a scale | Standard Deviation 4 |
Secondary
Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)
Change from baseline in possible range for Audit-C score is 0-12. Higher score indicates heavier use of alcohol. A score of \>=4 for male and a score of \>=3 for female meets the criteria for alcohol use disorders.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 10 | -0.4 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 18 | -0.2 scores on a scale | Standard Deviation 1.5 |
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 6 | -0.3 scores on a scale | Standard Deviation 1.7 |
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 22 | -0.2 scores on a scale | Standard Deviation 1.6 |
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 14 | -0.2 scores on a scale | Standard Deviation 1.6 |
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 26 | -0.3 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Baseline | 2 scores on a scale | Standard Deviation 2.8 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 26 | -0.3 scores on a scale | Standard Deviation 1.9 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Baseline | 2.2 scores on a scale | Standard Deviation 2.6 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 6 | -0.3 scores on a scale | Standard Deviation 1.7 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 10 | -0.2 scores on a scale | Standard Deviation 1.7 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 14 | -0.4 scores on a scale | Standard Deviation 2.2 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 18 | -0.1 scores on a scale | Standard Deviation 1.9 |
| Placebo Group | Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) | Change at Week 22 | -0.3 scores on a scale | Standard Deviation 2.1 |
Secondary
CAPS Recurrent Distressing Dreams Item
Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination) to assess temporal course of changes in symptoms in response to prazosin or placebo.
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Change at Week 10 | -1.9 scores on a scale | Standard Deviation 2.1 |
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Change at Week 18 | -1.8 scores on a scale | Standard Deviation 2.3 |
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Change at Week 6 | -1.3 scores on a scale | Standard Deviation 1.8 |
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Change at Week 22 | -2.4 scores on a scale | Standard Deviation 2.3 |
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Change at Week 14 | -2.2 scores on a scale | Standard Deviation 2.2 |
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Change at Week 26 | -2.3 scores on a scale | Standard Deviation 2.5 |
| Prazosin Group | CAPS Recurrent Distressing Dreams Item | Baseline | 6.3 scores on a scale | Standard Deviation 0.9 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Change at Week 26 | -2.2 scores on a scale | Standard Deviation 2.5 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Baseline | 6.3 scores on a scale | Standard Deviation 0.9 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Change at Week 6 | -1.4 scores on a scale | Standard Deviation 1.8 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Change at Week 10 | -1.7 scores on a scale | Standard Deviation 2.3 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Change at Week 14 | -2.5 scores on a scale | Standard Deviation 2.5 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Change at Week 18 | -2.4 scores on a scale | Standard Deviation 2.5 |
| Placebo Group | CAPS Recurrent Distressing Dreams Item | Change at Week 22 | -2.5 scores on a scale | Standard Deviation 2.4 |
Secondary
Clinical Global Impression of Change
Change from baseline in possible range for Clinical Global Impression of Change (CGIC) 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening.
Time frame: This secondary outcome measure was administered at 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | Clinical Global Impression of Change | Week 6 | 3.2 scores on a scale | Standard Deviation 1.2 |
| Prazosin Group | Clinical Global Impression of Change | Week 10 | 3.3 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Clinical Global Impression of Change | Week 14 | 3 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Clinical Global Impression of Change | Week 18 | 3.2 scores on a scale | Standard Deviation 1.3 |
| Prazosin Group | Clinical Global Impression of Change | Week 22 | 2.9 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Clinical Global Impression of Change | Week 26 | 2.9 scores on a scale | Standard Deviation 1.6 |
| Placebo Group | Clinical Global Impression of Change | Week 22 | 2.9 scores on a scale | Standard Deviation 1.3 |
| Placebo Group | Clinical Global Impression of Change | Week 6 | 3.3 scores on a scale | Standard Deviation 1.3 |
| Placebo Group | Clinical Global Impression of Change | Week 18 | 3 scores on a scale | Standard Deviation 1.4 |
| Placebo Group | Clinical Global Impression of Change | Week 10 | 3.3 scores on a scale | Standard Deviation 1.4 |
| Placebo Group | Clinical Global Impression of Change | Week 26 | 2.9 scores on a scale | Standard Deviation 1.4 |
| Placebo Group | Clinical Global Impression of Change | Week 14 | 3 scores on a scale | Standard Deviation 1.4 |
Secondary
Patient Health Questionnaire-9 (PHQ9)
Change from baseline in possible range for PHQ9 score is 0-27. Higher PHQ9 score indicates more severe depression.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 14 | -1.9 scores on a scale | Standard Deviation 5.2 |
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Baseline | 13.7 scores on a scale | Standard Deviation 5.9 |
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 18 | -1.6 scores on a scale | Standard Deviation 5.3 |
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 22 | -2.2 scores on a scale | Standard Deviation 5.6 |
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 10 | -1.9 scores on a scale | Standard Deviation 5.1 |
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 26 | -2 scores on a scale | Standard Deviation 5.5 |
| Prazosin Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 6 | -1.6 scores on a scale | Standard Deviation 4.7 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 26 | -2.8 scores on a scale | Standard Deviation 5.8 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Baseline | 14.6 scores on a scale | Standard Deviation 5.9 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 6 | -2.8 scores on a scale | Standard Deviation 5.1 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 10 | -2.2 scores on a scale | Standard Deviation 5.1 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 14 | -2.6 scores on a scale | Standard Deviation 5.3 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 22 | -2.5 scores on a scale | Standard Deviation 5.9 |
| Placebo Group | Patient Health Questionnaire-9 (PHQ9) | Change at Week 18 | -2.4 scores on a scale | Standard Deviation 5.5 |
Secondary
Pittsburgh Sleep Quality Index
Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | Pittsburgh Sleep Quality Index | Change at Week 10 | -2.3 scores on a scale | Standard Deviation 4.2 |
| Prazosin Group | Pittsburgh Sleep Quality Index | Change at Week 18 | -2.4 scores on a scale | Standard Deviation 4.1 |
| Prazosin Group | Pittsburgh Sleep Quality Index | Change at Week 6 | -2.1 scores on a scale | Standard Deviation 3.9 |
| Prazosin Group | Pittsburgh Sleep Quality Index | Change at Week 22 | -2.9 scores on a scale | Standard Deviation 4 |
| Prazosin Group | Pittsburgh Sleep Quality Index | Change at Week 14 | -3.1 scores on a scale | Standard Deviation 3.9 |
| Prazosin Group | Pittsburgh Sleep Quality Index | Change at Week 26 | -2.9 scores on a scale | Standard Deviation 4.3 |
| Prazosin Group | Pittsburgh Sleep Quality Index | Baseline | 14.4 scores on a scale | Standard Deviation 3.3 |
| Placebo Group | Pittsburgh Sleep Quality Index | Change at Week 26 | -2.7 scores on a scale | Standard Deviation 4.1 |
| Placebo Group | Pittsburgh Sleep Quality Index | Baseline | 14.7 scores on a scale | Standard Deviation 3.5 |
| Placebo Group | Pittsburgh Sleep Quality Index | Change at Week 6 | -2.4 scores on a scale | Standard Deviation 4.2 |
| Placebo Group | Pittsburgh Sleep Quality Index | Change at Week 10 | -2.1 scores on a scale | Standard Deviation 4 |
| Placebo Group | Pittsburgh Sleep Quality Index | Change at Week 14 | -2.7 scores on a scale | Standard Deviation 3.9 |
| Placebo Group | Pittsburgh Sleep Quality Index | Change at Week 18 | -2.8 scores on a scale | Standard Deviation 4 |
| Placebo Group | Pittsburgh Sleep Quality Index | Change at Week 22 | -2.7 scores on a scale | Standard Deviation 4.2 |
Secondary
PTSD Checklist-Military Version (PCL-M) Score
Change from baseline in possible range for PCL-M score 17-85. Higher PCL score indicates greater propensity for chronic and delayed PTSD.
Time frame: This secondary outcome was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks to assess change in PTSD symptom severity.
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 10 | -7 scores on a scale | Standard Deviation 12.7 |
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 18 | -7.2 scores on a scale | Standard Deviation 12.3 |
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 6 | -6.3 scores on a scale | Standard Deviation 10.6 |
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 22 | -7.1 scores on a scale | Standard Deviation 12.9 |
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 14 | -8.1 scores on a scale | Standard Deviation 12.5 |
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 26 | -8.2 scores on a scale | Standard Deviation 13.8 |
| Prazosin Group | PTSD Checklist-Military Version (PCL-M) Score | Baseline | 62.5 scores on a scale | Standard Deviation 11.1 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 26 | -9.7 scores on a scale | Standard Deviation 14 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Baseline | 64.3 scores on a scale | Standard Deviation 12.2 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 6 | -6.2 scores on a scale | Standard Deviation 11 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 10 | -5.8 scores on a scale | Standard Deviation 11.6 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 14 | -7.6 scores on a scale | Standard Deviation 11.6 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 18 | -8.4 scores on a scale | Standard Deviation 13.3 |
| Placebo Group | PTSD Checklist-Military Version (PCL-M) Score | Change at Week 22 | -9.2 scores on a scale | Standard Deviation 13.5 |
Secondary
Quality of Life Inventory (QOLI)
Change from baseline in possible range for QOLI is -6 to 6. Higher QOLI indicates better satisfaction with life.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | Quality of Life Inventory (QOLI) | Baseline | 0.1 scores on a scale | Standard Deviation 1.9 |
| Prazosin Group | Quality of Life Inventory (QOLI) | Change at Week 18 | 0.3 scores on a scale | Standard Deviation 1.3 |
| Prazosin Group | Quality of Life Inventory (QOLI) | Change at Week 10 | 0 scores on a scale | Standard Deviation 1.3 |
| Prazosin Group | Quality of Life Inventory (QOLI) | Change at Week 22 | 0.1 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Quality of Life Inventory (QOLI) | Change at Week 6 | 0.1 scores on a scale | Standard Deviation 1.5 |
| Prazosin Group | Quality of Life Inventory (QOLI) | Change at Week 26 | 0.2 scores on a scale | Standard Deviation 1.4 |
| Prazosin Group | Quality of Life Inventory (QOLI) | Change at Week 14 | 0.1 scores on a scale | Standard Deviation 1.5 |
| Placebo Group | Quality of Life Inventory (QOLI) | Change at Week 26 | 0.2 scores on a scale | Standard Deviation 2 |
| Placebo Group | Quality of Life Inventory (QOLI) | Baseline | 0 scores on a scale | Standard Deviation 1.9 |
| Placebo Group | Quality of Life Inventory (QOLI) | Change at Week 6 | 0 scores on a scale | Standard Deviation 1.4 |
| Placebo Group | Quality of Life Inventory (QOLI) | Change at Week 10 | 0.1 scores on a scale | Standard Deviation 1.7 |
| Placebo Group | Quality of Life Inventory (QOLI) | Change at Week 14 | 0 scores on a scale | Standard Deviation 1.5 |
| Placebo Group | Quality of Life Inventory (QOLI) | Change at Week 18 | 0.1 scores on a scale | Standard Deviation 1.6 |
| Placebo Group | Quality of Life Inventory (QOLI) | Change at Week 22 | 0.1 scores on a scale | Standard Deviation 1.9 |
Secondary
SF-12 Mental Standardized Score (SF-12 MCS)
Change from baseline in possible range for SF-12 MCS is 5-76. Higher SF-12 score indicates better level of health.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 10 | -1 scores on a scale | Standard Deviation 9.2 |
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 18 | -0.2 scores on a scale | Standard Deviation 8.4 |
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 6 | -2 scores on a scale | Standard Deviation 9.2 |
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 22 | -0.8 scores on a scale | Standard Deviation 8.9 |
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 14 | -1.5 scores on a scale | Standard Deviation 7.9 |
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 26 | -0.7 scores on a scale | Standard Deviation 8.7 |
| Prazosin Group | SF-12 Mental Standardized Score (SF-12 MCS) | Baseline | 38.2 scores on a scale | Standard Deviation 9.1 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 26 | -0.8 scores on a scale | Standard Deviation 9.5 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Baseline | 39.4 scores on a scale | Standard Deviation 8.4 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 6 | -1.3 scores on a scale | Standard Deviation 8.5 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 10 | -1.1 scores on a scale | Standard Deviation 8.7 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 14 | -1 scores on a scale | Standard Deviation 9.7 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 18 | -0.7 scores on a scale | Standard Deviation 8.8 |
| Placebo Group | SF-12 Mental Standardized Score (SF-12 MCS) | Change at Week 22 | -0.6 scores on a scale | Standard Deviation 9.4 |
Secondary
SF-12 Physical Standardized Score (SF-12 PCS)
Change from baseline in possible range for SF-12 PCS is 6-72. Higher SF-12 score indicates better level of health.
Time frame: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 10 | 0.3 scores on a scale | Standard Deviation 10 |
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 18 | 0.5 scores on a scale | Standard Deviation 10 |
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 6 | 1.8 scores on a scale | Standard Deviation 9.7 |
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 22 | 1.1 scores on a scale | Standard Deviation 10.9 |
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 14 | 1.4 scores on a scale | Standard Deviation 10.1 |
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 26 | 0.7 scores on a scale | Standard Deviation 11.8 |
| Prazosin Group | SF-12 Physical Standardized Score (SF-12 PCS) | Baseline | 35.4 scores on a scale | Standard Deviation 14.5 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 26 | -0.2 scores on a scale | Standard Deviation 11.9 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Baseline | 34.2 scores on a scale | Standard Deviation 12.2 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 6 | 0.8 scores on a scale | Standard Deviation 10.2 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 10 | 0.3 scores on a scale | Standard Deviation 10.4 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 14 | 0.3 scores on a scale | Standard Deviation 10.9 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 18 | -0.4 scores on a scale | Standard Deviation 11.4 |
| Placebo Group | SF-12 Physical Standardized Score (SF-12 PCS) | Change at Week 22 | -0.8 scores on a scale | Standard Deviation 13.2 |
Secondary
Total CAPS Score
Change from baseline in possible range for CAPS total score is 0-136. Higher score indicates more severe PTSD symptoms.
Time frame: The total CAPS was administered at baseline, 6, 10, 18, and 26 weeks (or early termination).
Population: 11 participants in the prazosin group have missing data on this item at one or more of the follow-up weeks; 9 participants in the placebo group have missing data at one or more of the follow-up weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prazosin Group | Total CAPS Score | Change at Week 6 | -9.9 scores on a scale | Standard Deviation 16 |
| Prazosin Group | Total CAPS Score | Change at Week 18 | -11.6 scores on a scale | Standard Deviation 18.3 |
| Prazosin Group | Total CAPS Score | Change at Week 10 | -11.4 scores on a scale | Standard Deviation 17.2 |
| Prazosin Group | Total CAPS Score | Change at Week 26 | -14.1 scores on a scale | Standard Deviation 21.8 |
| Prazosin Group | Total CAPS Score | Baseline | 80.7 scores on a scale | Standard Deviation 15.5 |
| Placebo Group | Total CAPS Score | Change at Week 26 | -16.2 scores on a scale | Standard Deviation 24.2 |
| Placebo Group | Total CAPS Score | Baseline | 81.9 scores on a scale | Standard Deviation 17.1 |
| Placebo Group | Total CAPS Score | Change at Week 6 | -9.1 scores on a scale | Standard Deviation 16.9 |
| Placebo Group | Total CAPS Score | Change at Week 10 | -12.1 scores on a scale | Standard Deviation 19.4 |
| Placebo Group | Total CAPS Score | Change at Week 18 | -17.2 scores on a scale | Standard Deviation 21.7 |