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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2010 by Massachusetts General Hospital.
Recruitment status was:  Recruiting
VA Office of Research and Development
Information provided by:
Massachusetts General Hospital Identifier:
First received: June 30, 2008
Last updated: April 27, 2010
Last verified: April 2010

The consolidation of learning is enhanced by adrenalin and other stress hormones. This memory enhancing effect is opposed by propranolol. In post-traumatic stress disorder (PTSD), a psychologically traumatic event may overstimulate stress hormones such as adrenalin, which in turn overly strengthen consolidation of the memory of the event, leading to an excessively powerful and persistent memory. Administration of propranolol after a psychologically traumatic event could reduce subsequent PTSD. Unfortunately, there exists a window of opportunity for influencing the consolidation of a traumatic event into long-term memory. In persons who have already developed PTSD, this would have closed months or years earlier. However, recent developments in animal research suggest that reactivation (retrieval) of a consolidated memory can return it to a labile state, from which it must be restabilized in order to persist. This process, which has been termed "reconsolidation," can be reduced in animals by propranolol.

In a preliminary study performed by the PI and colleagues in Canada, civilian subjects with PTSD described the traumatic event during a script preparation session, which served to reactivate their traumatic memory. They then received either propranolol or placebo. A week later, during script-driven imagery of their traumatic events, physiologic responses were smaller in the subjects who had received post-reactivation propranolol compared to placebo, suggesting that the traumatic memory had been weakened by the propranolol. These results suggest that that post-reactivation propranolol recapitulates its effects on consolidation, this time by blocking reconsolidation of the traumatic memory.

Several important questions remain unanswered. First, does propranolol also weaken traumatic memories in combat-related PTSD? Second, does this weakening effect only occur when the propranolol is given after combat memory reactivation? If not, this would refute the reconsolidation hypothesis and suggest that propranolol affects non-specific mechanisms. Third, how long does the traumatic memory weakening last?

The proposed project will investigate these questions by performing an improved, double-blind, placebo-controlled study in Iraq and Afghanistan veterans with combat-related PTSD. Subjects will be randomly assigned to one of two groups: post-reactivation propranolol or non-reactivation propranolol. Subjects in the non-reactivation propranolol group will receive propranolol in the absence of traumatic memory reactivation. Subjects randomized to the post-reactivation propranolol group will receive matching placebo capsules. Two days later, all subjects will return for a script preparation session, at which time they will describe the details of their traumatic event. Subjects randomized to the post-reactivation propranolol group will then receive propranolol, whereas subjects randomized to the non-reactivation propranolol group will receive placebo. Subjects will then return for psychophysiologic script-driven imagery testing one week and six months later. We hypothesize that those who receive propranolol after reactivation of their memories of their traumatic combat event(s) will show significantly smaller psychophysiologic responses during script-driven imagery testing compared to subjects who receive propranolol in the absence of combat memory reactivation, supporting the inference that post-reactivation propranolol blocks the reconsolidation of traumatic combat memories.

Condition Intervention Phase
Post-Traumatic Stress Disorder
Drug: Propranolol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Psychophysiologic responses during script-driven imagery of combat events [ Time Frame: 1 week, 6 months ]

Estimated Enrollment: 66
Study Start Date: May 2007
Estimated Study Completion Date: April 2011
Estimated Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Post-reactivation propranolol
Drug: Propranolol
0.67 mg/kg short-acting propranolol combined with 1 mg/kg long-acting propranolol
Active Comparator: 2
Non-reactivation propranolol
Drug: Propranolol
0.67 mg/kg short-acting propranolol combined with 1 mg/kg long-acting propranolol

  Show Detailed Description


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: Afghanistan and Iraq War veterans who have been diagnosed as having combat-related PTSD

Exclusion Criteria:

  1. PTSD Checklist (PCL) score (administered at the referring site) ≤ 50;
  2. Current, co-existing PTSD of non-combat origin
  3. Resting systolic blood pressure <100 mm Hg
  4. Medical condition that contraindicates the administration of propranolol
  5. Previous adverse reaction to, or non-compliance with, a β-adrenergic blocker
  6. Presence of drugs of abuse
  7. Pregnancy
  8. Contraindicating psychiatric condition
  9. Initiation of, or change in, psychotropic medication within the two months prior to recruitment
  10. Current use of medication that may involve potentially dangerous interactions with propranolol
  11. Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation
  12. Does not understand English
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00709735

Contact: Roger K Pitman, M.D. 617-726-5333

United States, Massachusetts
VA Medical Center Recruiting
Bedford, Massachusetts, United States, 01730
Contact: Lawrence Herz, M.D.    781-687-2494   
Sub-Investigator: Lawrence Herz, M.D.         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02108
United States, New Hampshire
VA Medical Center Recruiting
Manchester, New Hampshire, United States, 03104
Contact: Scott P. Orr, Ph.D.    603-624-4366 ext 6733   
Sub-Investigator: Scott P Orr, Ph.D.         
Sponsors and Collaborators
Massachusetts General Hospital
VA Office of Research and Development
Principal Investigator: Roger K Pitman, M.D. Massachusetts General Hospital
  More Information

Responsible Party: Roger K. Pitman, M.D., Massachusetts General Hospital Identifier: NCT00709735     History of Changes
Other Study ID Numbers: W81XWH-07-1-0440 
Study First Received: June 30, 2008
Last Updated: April 27, 2010

Keywords provided by Massachusetts General Hospital:
stress disorders, post-traumatic; memory; propranolol; psychophysiology

Additional relevant MeSH terms:
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents processed this record on March 01, 2017