Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Propranolol on Preventing Posttraumatic Stress Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00158262
Recruitment Status : Completed
First Posted : September 12, 2005
Results First Posted : April 10, 2017
Last Update Posted : April 10, 2017
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Roger K. Pitman, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Post-Traumatic Stress Disorder
Interventions Drug: Propranolol
Drug: Placebo
Enrollment 43
Recruitment Details  
Pre-assignment Details Participants who experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo.
Arm/Group Title Placebo Propranolol
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 21 22
Completed 20 21
Not Completed 1 1
Reason Not Completed
Lost to Follow-up             1             1
Arm/Group Title Placebo Propranolol Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 20 21 41
Hide Baseline Analysis Population Description
All randomized participants with data available for analysis. 1 participant in each arm dropped out prior to analysis and are excluded.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 21 participants 41 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
20
 100.0%
21
 100.0%
41
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 21 participants 41 participants
33.8  (9.4) 33.3  (11.0) 33.6  (10.2)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants 21 participants 41 participants
Female 7 10 17
Male 13 11 24
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 21 participants 41 participants
20 21 43
1.Primary Outcome
Title Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 1
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with data available for analysis at Month 1. Data were missing in 2 placebo and 2 propranolol participants.
Arm/Group Title Placebo Propranolol
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 18 19
Mean (Standard Deviation)
Unit of Measure: percent probability
40.7  (17.0) 33.7  (10.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Propranolol
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.0
Confidence Interval (2-Sided) 95%
-2.7 to 16.7
Estimation Comments Placebo-Propranolol
2.Primary Outcome
Title Physiological Posterior Probability of PTSD as Determined From Psychophysiologic Responses During Script-Driven Mental Imagery at Month 3
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with data available for analysis at Month 3. Data were missing in 6 placebo and 5 propranolol participants.
Arm/Group Title Placebo Propranolol
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: percent probability
34.9  (13.1) 32.0  (5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Propranolol
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-4.8 to 10.7
Estimation Comments Placebo-Propranolol
3.Secondary Outcome
Title Clinician-Administered PTSD Scale (CAPS) Total Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with CAPS data available for analysis at the given time-point.
Arm/Group Title Placebo Propranolol
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 20 21
Mean (Standard Deviation)
Unit of Measure: score on a scale
Month 1 Number Analyzed 20 participants 21 participants
28.5  (27.1) 28.5  (21.5)
Month 3 Number Analyzed 17 participants 17 participants
19.0  (25.8) 21.2  (26.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Propranolol
Comments CAPS Total Score at Month 1
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-15.5 to 15.3
Estimation Comments Placebo-Propranolol
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Propranolol
Comments CAPS Total Score at Month 3
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-20.3 to 16.0
Estimation Comments [Not Specified]
Time Frame Up to 3 Months
Adverse Event Reporting Description All randomized participants with data available for analysis. 1 participant in each arm dropped out prior to analysis and are excluded.
 
Arm/Group Title Placebo Propranolol
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Placebo Propranolol
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Propranolol
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/21 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Propranolol
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/21 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Roger K. Pitman, M.D.
Organization: Massachusetts General Hospital
Phone: 617-726-5333
Responsible Party: Roger K. Pitman, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00158262     History of Changes
Other Study ID Numbers: R01MH068603 ( U.S. NIH Grant/Contract )
R01MH068603 ( U.S. NIH Grant/Contract )
First Submitted: September 7, 2005
First Posted: September 12, 2005
Results First Submitted: May 7, 2013
Results First Posted: April 10, 2017
Last Update Posted: April 10, 2017