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A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol

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ClinicalTrials.gov Identifier: NCT00709735
Recruitment Status : Completed
First Posted : July 3, 2008
Results First Posted : April 10, 2017
Last Update Posted : April 10, 2017
Sponsor:
Collaborator:
VA Office of Research and Development
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: Treatment
Condition Posttraumatic Stress Disorder
Interventions Drug: Propranolol
Drug: Placebo
Enrollment 23
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Hide Arm/Group Description 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences. 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences.
Period Title: Overall Study
Started 11 12
Completed 8 10
Not Completed 3 2
Reason Not Completed
Lost to Follow-up             1             1
Relapse into Opioid Abuse             0             1
Did not meet PTSD Diagnostic Criteria             2             0
Arm/Group Title Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP) Total
Hide Arm/Group Description 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences. 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences. Total of all reporting groups
Overall Number of Baseline Participants 8 10 18
Hide Baseline Analysis Population Description
All randomized participants who completed the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 10 participants 18 participants
33.3  (11.5) 38.7  (14.9) 36.1  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 10 participants 18 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
8
 100.0%
10
 100.0%
18
 100.0%
Clinician-Administered PTSD Scale (CAPS) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 8 participants 10 participants 18 participants
58.6  (14.8) 62.7  (13.7) 60.9  (14.2)
[1]
Measure 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).
1.Primary Outcome
Title Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Traumatic Memory Recollection
Hide Description The posterior probability of developing PTSD was determined for each participant from a composite of psychophysiological responses during script-driven imagery of traumatic combat events 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 was used to calculate each participant’s posterior probability of being classified as PTSD.
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed the study.
Arm/Group Title Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Hide Arm/Group Description:
0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences.
0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences.
Overall Number of Participants Analyzed 8 10
Mean (Standard Deviation)
Unit of Measure: percent probability
32  (11) 45  (21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-Reactivation Propranolol (NRP), Reactivation Propranolol (RP)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.0
Confidence Interval (2-Sided) 95%
-30.0 to 4.0
Estimation Comments Non-Reactivation Propranolol (NRP) - Reactivation Propranolol (RP)
2.Secondary Outcome
Title Change From Baseline in the Impact of Event Scale-Revised (IES-R) Total Score
Hide Description IES-R is a 22-item patient reported measure of PTSD symptoms. Each question is answered using a 5-point scale where 0=not at all to 4=extremely for a total possible score of 0 to 88. Lower scores represent less severe symptoms and higher scores representing more severe symptoms. IES-R change scores were calculated by subtracting the Day 2 IES-R total score from the Day 8 IES-R total score. A negative change from Baseline indicates improvement of symptoms and a positive change from Baseline indicates a worsening of symptoms.
Time Frame Day 2 (Baseline ) and Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed the study.
Arm/Group Title Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Hide Arm/Group Description:
0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences.
0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences.
Overall Number of Participants Analyzed 8 10
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 43.3  (14.2) 45.0  (18.3)
Change from Baseline at Day 8 -8.2  (13.0) 4.5  (13.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-Reactivation Propranolol (NRP), Reactivation Propranolol (RP)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.7
Confidence Interval (2-Sided) 95%
-27.4 to 1.9
Estimation Comments Non-Reactivation Propranolol (NRP) - Reactivation Propranolol (RP)
Time Frame [Not Specified]
Adverse Event Reporting Description All randomized participants who received study drug,
 
Arm/Group Title Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Hide Arm/Group Description 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences. 0.67 mg/kg short-acting placebo capsules then 1 mg/kg long-acting placebo capsules 90 minutes later on Day 0 (non-reactivation) followed by 0.67 mg/kg short-acting propranolol capsules then 1 mg/kg long-acting propranolol capsules 90 minutes later on Day 2 (reactivation). All participants then underwent a “script preparation” session in which the investigator elicited five discrete personal memories, including two traumatic combat experiences.
All-Cause Mortality
Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/11 (0.00%)      1/12 (8.33%)    
Psychiatric disorders     
Relapse of substance abuse * [1]  0/11 (0.00%)  0 1/12 (8.33%)  1
*
Indicates events were collected by non-systematic assessment
[1]
One participant in the RP group was withdrawn from the study following his relapse into opioid abuse following his Day 2 participation. This relapse was attributed to the stress of narrating his traumatic event.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Non-Reactivation Propranolol (NRP) Reactivation Propranolol (RP)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/11 (0.00%)      0/12 (0.00%)    
Small participant sample due to recruitment difficulties.
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
Layout table for Results Point of Contact information
Name/Title: Roger K. Pitman, M.D.
Organization: Massachusetts General Hospital
Phone: 617-726-5333
EMail: roger_pitman@hms.harvard.edu
Layout table for additonal information
Responsible Party: Roger K. Pitman, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00709735     History of Changes
Other Study ID Numbers: W81XWH-07-1-0440
First Submitted: June 30, 2008
First Posted: July 3, 2008
Results First Submitted: May 1, 2012
Results First Posted: April 10, 2017
Last Update Posted: April 10, 2017