Post-Traumatic Stress DisorderPhase 4NCT00158262
Effect of Propranolol on Preventing Posttraumatic Stress Disorder
A Phase 4 study testing Propranolol in people with Post-Traumatic Stress Disorder, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Post-Traumatic Stress Disorder
- What is being tested?
- Propranolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2004to May 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Experienced an acute psychological traumatic event
- Heart rate of 80 beats per minute (bpm) or greater
- Understands English
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Prophylaxis of Posttraumatic Stress Disorder With Post-Trauma Propranolol
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.
Read the 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.
- Conditions
- Post-Traumatic Stress Disorder
- Being tested
- Propranolol, Placebo
- Keywords
- Post-Traumatic Stress Disorder, Prevention, Propranolol, Psychophysiology
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Also called Inderal
Propranolol short-acting or long-acting capsule
PlaceboDrug
Placebo-matching propranolol short-acting or long-acting capsule
| Study group | Role | What they receive |
|---|---|---|
| Propranolol | Experimental | 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. Receives: Drug: Propranolol |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 1
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.
Measured: Month 3
Secondary outcomes (1)
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).
Measured: Months 1 and 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startSep 2004
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Post-Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Roger K. Pitman, MD, Massachusetts General Hospital
- Investigators
- Roger K. Pitman, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00158262
- Sponsor's protocol ID
- R01MH068603
- Other IDs
- R01MH068603
- Status last verified
- Apr 2017
- First submitted
- 7 Sep 2005
- Last updated
- 10 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hoge EA, Worthington JJ, Nagurney JT, Chang Y, Kay EB, Feterowski CM, Katzman AR, Goetz JM, Rosasco ML, Lasko NB, Zusman RM, Pollack MH, Orr SP, Pitman RK. Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery. CNS Neurosci Ther. 2012 Jan;18(1):21-7. doi: 10.1111/j.1755-5949.2010.00227.x. Epub 2011 Jan 10.
PubMed 22070357Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.
PubMed 38767196Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.
PubMed 35141873
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylaxis of Posttraumatic Stress Disorder With Post-Trauma Propranolol
- ClinicalTrials.gov ID
- NCT00158262
- Acronym / sponsor ID
- R01MH068603
- Conditions
- Post-Traumatic Stress Disorder
- Keywords
- Post-Traumatic Stress Disorder, Prevention, Propranolol, Psychophysiology
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Sep 2004 (actual)
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 10 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propranolol | Experimental | Drug: PropranololFollowing 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. |
| Placebo | Placebo comparator | Drug: PlaceboFollowing 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Experienced an acute psychological traumatic event
- Heart rate of 80 beats per minute (bpm) or greater
- Understands English
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropranololAlso: InderalPropranolol short-acting or long-acting capsule | Drug | Propranolol |
| PlaceboPlacebo-matching propranolol short-acting or long-acting capsule | Drug | Placebo |
Primary outcome
Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1
Time frame: 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
Time frame: 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.
1 secondary outcome
Clinician-Administered PTSD Scale (CAPS) Total Score
Time frame: Months 1 and 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22070357Hoge EA, Worthington JJ, Nagurney JT, Chang Y, Kay EB, Feterowski CM, Katzman AR, Goetz JM, Rosasco ML, Lasko NB, Zusman RM, Pollack MH, Orr SP, Pitman RK. Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery. CNS Neurosci Ther. 2012 Jan;18(1):21-7. doi: 10.1111/j.1755-5949.2010.00227.x. Epub 2011 Jan 10.
- Derived from this study: PubMed 38767196Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.
- Derived from this study: PubMed 35141873Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger K. Pitman, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propranolol in people with Post-Traumatic Stress Disorder, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1 (time frame: Month 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00158262, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2017.