PTSD Symptom Reduction by Propranolol Given After Trauma Memory Activation
Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Posttraumatic Stress Disorders
Intervention: Propranolol (Drug); Placebo (Drug)
Phase: Phase 4
Sponsored by: Department of Veterans Affairs
Official(s) and/or principal investigator(s):
Scott P Orr, PhD, Principal Investigator, Affiliation: VA Medical Center, Manchester
OBJECTIVE: In the first of two preliminary studies, we demonstrated in individuals with
chronic PTSD that a single (combined 40 mg short- and 60 mg long-acting) 24-hour oral dose
of propranolol, compared to placebo, given immediately following reactivation of the
PTSD-related memory of the traumatic event, significantly reduced physiological responses
during script-driven imagery of that event measured one week later. These results support
blockade of reconsolidation of the traumatic memory, a process that is entirely distinct
from extinction. In addition, we found a trend for post-reactivation propranolol to reduce
self-reported PTSD symptoms, measured via the Impact of Event Scale-Revised (IES-R). In the
second preliminary study, we performed 6 weekly treatments that consisted of the subject
describing their PTSD-related traumatic events for approximately 10 minutes followed by 0. 67
mg/kg (minimum 40 mg) short-acting propranolol plus 1 mg/kg (minimum 60 mg) long-acting
propranolol. The mean Clinician Administered PTSD Scale (CAPS) Total Score following the six
treatment sessions was reduced by 44% (p=.02). The proposed work will examine whether
repeated treatments may succeed in producing more substantive symptomatic improvement.
RESEARCH PLAN: The study design will be a randomized, double-blind, placebo-controlled,
clinical trial. A crossover design is not being proposed because the effect is expected to
be neither short-term nor reversible. Rather, at the conclusion of the formal study period,
individuals randomized to the placebo condition will be offered an equal number of treatment
sessions with propranolol. A placebo control will be used, rather than an active treatment
control, because the proposed study will be a "proof of concept" test of post-reactivation
pharmacological reduction of traumatic memories. The control (and active) treatments will be
structured so as to minimize the chance of extinction. We recognize that eventually this new
treatment will need to be tested against established PTSD treatments, including exposure, if
its clinical utility is to be established. We regard this as a matter for subsequent studies
should the present study yield promising results. However, we do intend to compare the
effect size we find for the proposed intervention with published effect sizes for other PTSD
METHODOLOGY: Participants will include male and female combat veterans of the Afghanistan
and Iraqi wars meeting DSM-IV criteria for chronic PTSD, recruited locally from the
Manchester VAMC Mental Hygiene Clinic or through advertising. The presence of PTSD will be
assessed using the CAPS. Participants will be randomly assigned to the propranolol or
placebo drug condition. During each of six memory reactivation sessions, the participant
will meet with a psychiatrist, who will ask the participant to spend ten minutes describing
the event that caused their PTSD, and their reactions to it. The interviewer will facilitate
this process by asking questions, keeping the participant focused on the traumatic event and
encouraging him/her to identify aspects of the traumatic event that continue to provoke
emotional distress. The traumatic memory reactivation will be immediately followed by
administration of propranolol or placebo. Following the six treatment sessions,
script-driven imagery will be used to assess HR, SC, and facial EMG responses to
recollections of the traumatic event and PTSD symptoms will be assessed using the CAPS. A
previously developed discriminant function will be used to classify each person as a
physiologic "responder" or "non-responder." There will also be a 6-month follow-up
CLINICAL RELEVANCE: The mechanism of memory reconsolidation offers the possibility that
cellular plasticity can be capitalized on to reverse the neuroanatomical and
neurophysiological underpinnings of traumatic memories. The possibility that a traumatic
memory could be significantly weakened by an intervention as simple as the post-reactivation
administration of a widely used and safe medication has profound implications for the
treatment of PTSD.
Official title: PTSD Symptom Reduction by Propranolol Given After Memory Activation
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: PTSD symptom severity as measured by clinician administered PTSD scale
Minimum age: 18 Years.
Maximum age: 65 Years.
OEF/OIF veteran diagnosed with combat related posttraumatic stress disorder
1. Not diagnosed with current, chronic PTSD
2. Current PTSD related to a traumatic event other than the event being treated
4. Systolic blood pressure <100 mm HG or resting HR less than 60 BPM.
5. Medical condition that contraindicates the administration of propranolol, e. g.
history of congestive heart failure, heart block, insulin-requiring diabetes, chronic
bronchitis, emphysema, or asthma. With regard to asthma, because many persons who
say they have had an asthma attack, especially as a child, may only have had hay
fever, another allergy, or another non-asthmatic episode, a blanket exclusion
criteria may be overly restrictive. Therefore asthma attacks will only be
exclusionary if they a) occurred within the past 10 years, b) occurred at any time in
life if induced by a beta-blocker, or c) are currently being treated, regardless of
the date of last occurrence. Cardiological consultation will be obtained as
6. Previous adverse reaction to, or non-compliance with a beta-blocker.
7. Current use of medication that may involve potentially dangerous interactions with
propranolol, including, other beta-blockers, antiarrhythmics, calcium channel
blockers, and potent P450 2D6 inhibitors, e. g., fluoxetine, paroxetine, micnazole,
sulconazole, metaclopramide, quinidine, ticlopidine, and ritnavir.
8. Presence of drugs of abuse, viz., opiates, marijuana, cocaine, or amphetamines, as
determined by urine testing.
9. Pregnancy (in women of child- bearing potential, a pregnancy test will be performed)
or breast feeding.
10. Contraindicating psychiatric condition, e. g., current psychotic, bipolar,
melancholic, or substance dependence or abuse disorder.
11. Initiation of, or change in, psychotropic medication within the previous two months.
For subjects receiving stable doses of pharmacotherapy, they and their providers will
be asked not to change the regimen except in clinically urgent circumstances. If
this becomes necessary, a decision will be made on a case-by-case basis whether to
retain the subject in the study or terminate participation.
12. Current participation in any psychotherapy (other than supportive). Subjects will be
asked not to initiate psychotherapy during the course of the proposed study except in
clinically urgent circumstances; if this becomes necessary, a decision will be made
on a case-by-case basis whether to retain the subject in the study or terminate
13. Inability to understand the study's procedures, risks, and side effects, or to
otherwise give informed consent for participation.
Locations and Contacts
VA Medical Center, Manchester, Manchester, New Hampshire 03104, United States
Starting date: April 2008
Last updated: November 19, 2013