Trial Outcomes & Findings for A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol (NCT NCT00709735)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

23 participants

Primary outcome timeframe

Day 8

Results posted on

2017-04-10

Participant Flow

Participant milestones

Participant milestones
Measure	Non-Reactivation Propranolol (NRP) 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.	Reactivation Propranolol (RP) 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 Study STARTED	11	12
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Non-Reactivation Propranolol (NRP) 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.	Reactivation Propranolol (RP) 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 Study Lost to Follow-up	1	1
Overall Study Relapse into Opioid Abuse	0	1
Overall Study Did not meet PTSD Diagnostic Criteria	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-Reactivation Propranolol (NRP) n=8 Participants 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.	Reactivation Propranolol (RP) n=10 Participants 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 n=18 Participants Total of all reporting groups
Age, Continuous	33.3 years STANDARD_DEVIATION 11.5 • n=5 Participants	38.7 years STANDARD_DEVIATION 14.9 • n=7 Participants	36.1 years STANDARD_DEVIATION 13.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Clinician-Administered PTSD Scale (CAPS) Score	58.6 score on a scale STANDARD_DEVIATION 14.8 • n=5 Participants	62.7 score on a scale STANDARD_DEVIATION 13.7 • n=7 Participants	60.9 score on a scale STANDARD_DEVIATION 14.2 • n=5 Participants

PRIMARY outcome

Timeframe: Day 8

Population: All randomized participants who completed the study.

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.

Outcome measures

Outcome measures
Measure	Non-Reactivation Propranolol (NRP) n=8 Participants 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.	Reactivation Propranolol (RP) n=10 Participants 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.
Physiological Posterior Probability of Posttraumatic Stress Disorder (PTSD) as Determined From Psychophysiologic Responses During Script-Driven Traumatic Memory Recollection	32 percent probability Standard Deviation 11	45 percent probability Standard Deviation 21

SECONDARY outcome

Timeframe: Day 2 (Baseline ) and Day 8

Population: All randomized participants who completed the study.

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.

Outcome measures

Outcome measures
Measure	Non-Reactivation Propranolol (NRP) n=8 Participants 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.	Reactivation Propranolol (RP) n=10 Participants 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.
Change From Baseline in the Impact of Event Scale-Revised (IES-R) Total Score Baseline	43.3 score on a scale Standard Deviation 14.2	45.0 score on a scale Standard Deviation 18.3
Change From Baseline in the Impact of Event Scale-Revised (IES-R) Total Score Change from Baseline at Day 8	-8.2 score on a scale Standard Deviation 13.0	4.5 score on a scale Standard Deviation 13.2

Adverse Events

Non-Reactivation Propranolol (NRP)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Reactivation Propranolol (RP)

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Non-Reactivation Propranolol (NRP) n=11 participants at risk 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.	Reactivation Propranolol (RP) n=12 participants at risk 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.
Psychiatric disorders Relapse of substance abuse	0.00% 0/11 All randomized participants who received study drug,	8.3% 1/12 • Number of events 1 All randomized participants who received study drug,

Other adverse events

Adverse event data not reported

Additional Information

Roger K. Pitman, M.D.

Massachusetts General Hospital

Phone: 617-726-5333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place