Effect of Propranolol on Preventing Posttraumatic Stress Disorder

NCT00158262 | Completed Phase 4 Results DMC

• 1 other identifier: R01MH068603
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Post-Traumatic Stress Disorder

Keywords

Post-Traumatic Stress Disorder; Prevention; Propranolol; Psychophysiology

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Month 3

Secondary Outcomes (1)

• Clinician-Administered PTSD Scale (CAPS) Total Score

  Months 1 and 3

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Propranolol DRUG

Propranolol short-acting or long-acting capsule

Also known as: Inderal

Propranolol

Placebo DRUG

Placebo-matching propranolol short-acting or long-acting capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Experienced an acute psychological traumatic event
• Heart rate of 80 beats per minute (bpm) or greater
• Understands English

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• 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.

  PMID: 22070357 RESULT

• Bertolini 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.

  PMID: 38767196 DERIVED

• Bertolini 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.

  PMID: 35141873 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Roger K. Pitman, M.D.
• Organization: Massachusetts General Hospital

roger_pitman@hms.harvard.edu

617-726-5333

Study Officials

• Roger K. Pitman, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 7, 2005
• First Posted: September 12, 2005
• Study Start: September 1, 2004
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: April 10, 2017
• Results First Posted: April 10, 2017

Record last verified: 2017-04

Locations

US (2)