Post-Traumatic Stress Disorder
Conditions
Keywords
Propanolol, Beta Blockers, Reconsolidation, Cognitive Therapy, PTSD
Brief summary
This study will evaluate the effectiveness of propranolol in reducing symptoms of distress in people with post-traumatic stress disorder.
Detailed description
Post-traumatic stress disorder (PTSD) is a common and disabling condition, with about 10% of people having experienced PTSD at some point during their lives. The diagnosis of PTSD requires certain criteria: exposure to a severe psychological trauma and the persistent presence of three symptom clusters that include re-experiencing the traumatic event, physiologic hyperarousal, and emotional numbing paired with avoidance of stimuli associated with the event. Stimuli and cues associated with the trauma, such as features of an assailant or accident site, can cause a person to re-experience the traumatic memory and associated feelings of helplessness and fear. When re-experiencing a traumatic memory, people with PTSD usually undergo a heightened stress-related hormonal response that further solidifies new stimulating associations with the traumatic memory. Treatment with propranolol, a blood pressure-lowering drug that reduces stress-related hormonal responses, may be an effective means of preventing the formation of traumatic memories and of improving PTSD symptoms. This study will evaluate the effectiveness of propranolol in reducing symptoms of distress associated with traumatic memories in people with PTSD. Participation in this study will last 14 weeks. All potential participants will undergo a 4-hour initial visit that will begin with a medical and psychiatric history review, a psychiatric interview, and symptom questionnaires. Participants will then be assigned randomly to take a test dose of either propranolol or placebo. Upon completion of the test dose, participants will begin 14 weeks of treatment with their assigned test dose medication. Participants will be asked to take the study medication each time they have a traumatic memory associated with hyperarousal symptoms, but no more than two times a day. Using a cognitive behavioral therapy based-workbook, participants will track their symptoms daily and when they use cognitive techniques to relieve symptoms. Participants will attend study visits every 2 weeks for the 14 weeks of treatment. During these visits, participants will describe any side effects experienced, complete interviews and questionnaires about PTSD symptom severity, review with study officials their daily workbook entries, and pick up medication. Study participation will end upon completion of the Week 14 study visit. For information on a related study, please follow this link: http://clinicaltrials.gov/show/NCT00391430
Interventions
DRUGPropanolol
Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours.
DRUGPlacebo
Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours.
BEHAVIORALCognitive therapy workbook
Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Sponsors
National Institute of Mental Health (NIMH)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV diagnosis of PTSD or meets the five of the six diagnostic criteria for PTSD (event, hyperarousal, re-experiencing, duration, and distress/impaired functioning symptom criteria), but not the avoidance/numbing symptom criteria
Exclusion criteria
* Past or current asthma * Diabetes or heart disease * Currently pregnant or breastfeeding * Concurrent use of daily benzodiazepine; daily use of antidepressant medication allowed if dose has been stable for the 3 months before study entry * Exposure therapy or additional cognitive therapy during the course of the study (supportive psychotherapy is allowed if ongoing for at least 3 months before study entry) * Substance abuse * Current use of beta blockers, amiodarone, chlorpromazine, cimetidine, clonidine, or digoxin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Measured at Week 0, 2,4,6,8,10,12,14 | Scores range from 0-70, higher scores represent more severe symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Post-traumatic Scale-Self Score (PS-SR) | Measured at Weeks 0,2,4,6,8,10,12, 14 | This is a 17-item self-report scale. Scores range from 0-51, higher scores represent more severe symptoms. |
| Change in Depression Measured by Beck Depression Inventory (BDI) | Measured at Weeks 0,2,4,6,8,10,12, 14 | Scores range from 0-30, higher scores represent more severe symptoms |
| Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Measured at Weeks 0,2,4,6,8,10,12, 14 | BSI-SF is an 18 item scale used for a global score of general distress. Scores range from 0-72, higher scores represent more severe symptoms |
Countries
United States
Participant flow
Pre-assignment details
12 subjects were screened for the study. 3 subjects met enrollment criteria and were randomized to study medication.
Participants by arm
| Arm | Count |
|---|---|
| Propranolol Participants will take propranolol for 14 weeks.
Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours.
Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day. | 1 |
| Placebo Participants will take placebo for 14 weeks.
Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours.
Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day. | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Propranolol | Total | Placebo |
|---|---|---|---|
| Age, Continuous age | 42 years | 38.3 years | 36.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 1 participants | 3 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX)
Scores range from 0-70, higher scores represent more severe symptoms
Time frame: Measured at Week 0, 2,4,6,8,10,12,14
Population: 3 subjects enrolled in the study and completed all study visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 14 | 27 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Baseline | 58 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 2 | 62 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 4 | 56 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 6 | 45 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 8 | 40 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 10 | 32 score on a scale |
| Propranolol | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 12 | 29 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 12 | 35 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 14 | 28 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 6 | 44 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Baseline | 59 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 10 | 35 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 2 | 60 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 8 | 45.5 score on a scale |
| Placebo | Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) | Week 4 | 49.5 score on a scale |
Secondary
Change in Brief Symptoms Inventory-Short Form (BSI-SF)
BSI-SF is an 18 item scale used for a global score of general distress. Scores range from 0-72, higher scores represent more severe symptoms
Time frame: Measured at Weeks 0,2,4,6,8,10,12, 14
Population: 3 subjects were randomized, one to propranolol and one to placebo. The total number of subjects was too low to perform statistical analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Baseline | 28 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 2 | 34 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 4 | 30 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 6 | 28 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 8 | 32 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 10 | 26 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 12 | 23 score on a scale |
| Propranolol | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 14 | 18 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 14 | 20 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Baseline | 41 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 8 | 32 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 2 | 42 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 12 | 24.5 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 4 | 35 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 10 | 25 score on a scale |
| Placebo | Change in Brief Symptoms Inventory-Short Form (BSI-SF) | Week 6 | 31 score on a scale |
Secondary
Change in Depression Measured by Beck Depression Inventory (BDI)
Scores range from 0-30, higher scores represent more severe symptoms
Time frame: Measured at Weeks 0,2,4,6,8,10,12, 14
Population: 3 subjects were enrolled and randomized: one to active propranolol and two to placebo. Total number of subjects was too low to perform statistical analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Baseline | 12 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 2 | 11 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 4 | 12 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 6 | 9 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 8 | 9 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 10 | 7 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 12 | 7 score on a scale |
| Propranolol | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 14 | 6 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 14 | 7 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Baseline | 13 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 8 | 10 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 2 | 13 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 12 | 8.5 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 4 | 9.5 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 10 | 7.5 score on a scale |
| Placebo | Change in Depression Measured by Beck Depression Inventory (BDI) | Week 6 | 9.5 score on a scale |
Secondary
Change in Post-traumatic Scale-Self Score (PS-SR)
This is a 17-item self-report scale. Scores range from 0-51, higher scores represent more severe symptoms.
Time frame: Measured at Weeks 0,2,4,6,8,10,12, 14
Population: 3 subject were enrolled: 1 was randomized to propranolol and 2 were randomized to placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Baseline | 36 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 2 | 38 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 4 | 38 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 6 | 30 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 8 | 28 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 10 | 18 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 12 | 19 score on a scale |
| Propranolol | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 14 | 17 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 14 | 20.5 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Baseline | 42.5 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 8 | 32 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 2 | 42.5 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 12 | 24 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 4 | 36.5 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 10 | 26.5 score on a scale |
| Placebo | Change in Post-traumatic Scale-Self Score (PS-SR) | Week 6 | 35.5 score on a scale |