Post-Traumatic Stress Disorder
Conditions
Keywords
Post-Traumatic Stress Disorder, Prevention, Propranolol, Psychophysiology
Brief summary
This study will assess the effectiveness of taking propranolol soon after a traumatizing incident in reducing the incidence and severity of posttraumatic stress disorder in acutely traumatized individuals.
Detailed description
Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder that can occur following exposure to a traumatic event in which grave physical harm occurred or was threatened. PTSD is marked by clear biological changes as well as psychological symptoms. Many people with PTSD repeatedly relive the trauma in the form of flashback episodes, memories, nightmares, or frightening thoughts. This study will assess the effect of post-trauma propranolol on reducing the incidence and severity of PTSD. The study will also evaluate propranolol's effectiveness as a preventive measure against subsequent PTSD symptoms. Participants in this double-blind study will be recruited upon admission to the Massachusetts General Hospital Emergency Department after exposure to a psychologically traumatic event. Baseline psychometric and psychobiologic measurements will be collected. Within 6 hours following the traumatic event, participants will be randomly assigned to receive either 40 mg of short-acting propranolol or placebo and 60 mg of either long-acting propranolol or placebo. For the next 10 days, participants will receive 120 mg of either long-acting propranolol or placebo twice daily. A 9-day medication tapering will follow. Participants will undergo psychophysiologic, psychodiagnostic, and psychometric testing for PTSD 1 and 3 months following the traumatic event.
Interventions
DRUGPropranolol
Propranolol short-acting or long-acting capsule
DRUGPlacebo
Placebo-matching propranolol short-acting or long-acting capsule
Sponsors
National Institute of Mental Health (NIMH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Experienced an acute psychological traumatic event * Heart rate of 80 beats per minute (bpm) or greater * Understands English
Exclusion criteria
* Traumatic event that occurred more than four hours before arrival to emergency department * Physical injury that may affect safe participation (e.g., head injury) * Systolic blood pressure less than 100 mm Hg * Medical or surgical condition that poses a risk of shock * Medical condition that may affect the safe administration of propranolol * Previous adverse reaction to, or non-compliance with, a beta-blocker * Current use of medication that may react badly with propranolol * Elevated saliva alcohol level * Presence of salivary opiates, marijuana, cocaine, or amphetamines * Pregnant or breastfeeding * Traumatic event reflecting ongoing victimization * Psychiatric condition that may affect safe participation * Unwilling or unable to commute to Boston for research visits * Attending physician in emergency department does not advise participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1 | Month 1 | The posterior probability of developing PTSD was determined for each participant from a composite of psychophysiological responses during script-driven mental imagery of traumatic events (two exemplars) that included assessments of heart rate response in beats per minute, skin conductance response in microSiemens, and corrugator and left lateral frontalis facial muscle electromyogram (EMG) responses in microVolts. Responses for the two traumatic scripts were averaged and square-root transformed for analysis. Responses during personal traumatic imagery of previously studied individuals with and without current PTSD were used to calculate each participant's posterior probability of being classified as PTSD. |
| Physiological Posterior Probability of PTSD as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 3 | Month 3 | The posterior probability of developing PTSD was determined for each participant from a composite of psychophysiological responses during script-driven mental imagery of traumatic events (two exemplars) that included assessments of heart rate response in beats per minute, skin conductance response in microSiemens, and corrugator and left lateral frontalis facial muscle electromyogram (EMG) responses in microVolts. Responses for the two traumatic scripts were averaged and square-root transformed for analysis. Responses during personal traumatic imagery of previously studied individuals with and without current PTSD were used to calculate each participant's posterior probability of being classified as PTSD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered PTSD Scale (CAPS) Total Score | Months 1 and 3 | The clinician evaluated the overall frequency and intensity/severity of the participant's PTSD symptoms using the CAPS. 17 Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) PTSD symptoms were assessed using a 5-point scale for intensity where 0=none to 4=extreme and a 5-point scale for frequency where 0=never to 4=most or all of the time. The intensity score and the frequency scores were added together for a total possible score of 0 (best) to 136 (worst). |
Countries
United States
Participant flow
Pre-assignment details
Participants who experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Following the occurrence of an acute psychologically traumatic event, an initial dose of placebo-matching short-acting propranolol 40 mg orally then one hour later, placebo-matching long-acting propranolol 60 mg capsule orally on Day 1 followed by a 19-day course of placebo-matching long-acting propranolol starting with 120 mg every morning and evening for 10 days, and then tapering to 120 mg in the morning and 60 mg in the evening for 3 days, then 60 mg in the morning and 60 mg the evening for 3 days, then 60 mg in the morning for 3 days. | 20 |
| Propranolol Following the occurrence of an acute psychologically traumatic event, an initial dose of short-acting propranolol 40 mg orally then one hour later, long-acting propranolol 60 mg capsule orally on Day 1 followed by a 19-day course of long-acting propranolol starting with 120 mg every morning and evening for 10 days, and then tapering to 120 mg in the morning and 60 mg in the evening for 3 days, then 60 mg in the morning and 60 mg the evening for 3 days, then 60 mg in the morning for 3 days. | 21 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Propranolol | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 20 Participants | 41 Participants |
| Age, Continuous | 33.3 years STANDARD_DEVIATION 11 | 33.8 years STANDARD_DEVIATION 9.4 | 33.6 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment United States | 21 participants | 20 participants | 43 participants |
| Sex/Gender, Customized Female | 10 participants | 7 participants | 17 participants |
| Sex/Gender, Customized Male | 11 participants | 13 participants | 24 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1
The posterior probability of developing PTSD was determined for each participant from a composite of psychophysiological responses during script-driven mental imagery of traumatic events (two exemplars) that included assessments of heart rate response in beats per minute, skin conductance response in microSiemens, and corrugator and left lateral frontalis facial muscle electromyogram (EMG) responses in microVolts. Responses for the two traumatic scripts were averaged and square-root transformed for analysis. Responses during personal traumatic imagery of previously studied individuals with and without current PTSD were used to calculate each participant's posterior probability of being classified as PTSD.
Time frame: Month 1
Population: All randomized participants with data available for analysis at Month 1. Data were missing in 2 placebo and 2 propranolol participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1 | 40.7 percent probability | Standard Deviation 17 |
| Propranolol | Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1 | 33.7 percent probability | Standard Deviation 10.2 |
95% CI: [-2.7, 16.7]
Primary
Physiological Posterior Probability of PTSD as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 3
The posterior probability of developing PTSD was determined for each participant from a composite of psychophysiological responses during script-driven mental imagery of traumatic events (two exemplars) that included assessments of heart rate response in beats per minute, skin conductance response in microSiemens, and corrugator and left lateral frontalis facial muscle electromyogram (EMG) responses in microVolts. Responses for the two traumatic scripts were averaged and square-root transformed for analysis. Responses during personal traumatic imagery of previously studied individuals with and without current PTSD were used to calculate each participant's posterior probability of being classified as PTSD.
Time frame: Month 3
Population: All randomized participants with data available for analysis at Month 3. Data were missing in 6 placebo and 5 propranolol participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Physiological Posterior Probability of PTSD as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 3 | 34.9 percent probability | Standard Deviation 13.1 |
| Propranolol | Physiological Posterior Probability of PTSD as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 3 | 32.0 percent probability | Standard Deviation 5.8 |
95% CI: [-4.8, 10.7]
Secondary
Clinician-Administered PTSD Scale (CAPS) Total Score
The clinician evaluated the overall frequency and intensity/severity of the participant's PTSD symptoms using the CAPS. 17 Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) PTSD symptoms were assessed using a 5-point scale for intensity where 0=none to 4=extreme and a 5-point scale for frequency where 0=never to 4=most or all of the time. The intensity score and the frequency scores were added together for a total possible score of 0 (best) to 136 (worst).
Time frame: Months 1 and 3
Population: All randomized participants with CAPS data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Clinician-Administered PTSD Scale (CAPS) Total Score | Month 1 | 28.5 score on a scale | Standard Deviation 27.1 |
| Placebo | Clinician-Administered PTSD Scale (CAPS) Total Score | Month 3 | 19.0 score on a scale | Standard Deviation 25.8 |
| Propranolol | Clinician-Administered PTSD Scale (CAPS) Total Score | Month 1 | 28.5 score on a scale | Standard Deviation 21.5 |
| Propranolol | Clinician-Administered PTSD Scale (CAPS) Total Score | Month 3 | 21.2 score on a scale | Standard Deviation 26.1 |
Comparison: CAPS Total Score at Month 195% CI: [-15.5, 15.3]
Comparison: CAPS Total Score at Month 395% CI: [-20.3, 16]