Trial Outcomes & Findings for Effect of Propranolol on Preventing Posttraumatic Stress Disorder (NCT NCT00158262)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

43 participants

Primary outcome timeframe

Month 1

Results posted on

2017-04-10

Participant Flow

Participants who experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	21	22
Overall Study COMPLETED	20	21
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

Effect of Propranolol on Preventing Posttraumatic Stress Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=20 Participants 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.	Propranolol n=21 Participants 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 n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	33.8 years STANDARD_DEVIATION 9.4 • n=5 Participants	33.3 years STANDARD_DEVIATION 11.0 • n=7 Participants	33.6 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex/Gender, Customized Female	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Sex/Gender, Customized Male	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	21 participants n=7 Participants	43 participants n=5 Participants

PRIMARY outcome

Timeframe: Month 1

Population: All randomized participants with data available for analysis at Month 1. Data were missing in 2 placebo and 2 propranolol participants.

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.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants 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.	Propranolol n=19 Participants 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.
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 17.0	33.7 percent probability Standard Deviation 10.2

PRIMARY outcome

Timeframe: Month 3

Population: All randomized participants with data available for analysis at Month 3. Data were missing in 6 placebo and 5 propranolol participants.

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.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants 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.	Propranolol n=16 Participants 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.
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	32.0 percent probability Standard Deviation 5.8

SECONDARY outcome

Timeframe: Months 1 and 3

Population: All randomized participants with CAPS data available for analysis at the given time-point.

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).

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants 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.	Propranolol n=21 Participants 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.
Clinician-Administered PTSD Scale (CAPS) Total Score Month 1	28.5 score on a scale Standard Deviation 27.1	28.5 score on a scale Standard Deviation 21.5
Clinician-Administered PTSD Scale (CAPS) Total Score Month 3	19.0 score on a scale Standard Deviation 25.8	21.2 score on a scale Standard Deviation 26.1

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Propranolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

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