PTSD Symptom Reduction by Propranolol Given After Trauma Memory Activation

This study has been terminated.
(Difficulty recruiting subjects and unable to replace study physician who changed jobs)
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00645450
First received: March 19, 2008
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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 psychotherapies.

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 assessment.

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.


Condition Intervention Phase
Posttraumatic Stress Disorders
Drug: Propranolol
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PTSD Symptom Reduction by Propranolol Given After Memory Activation

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • PTSD symptom severity as measured by clinician administered PTSD scale [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: April 2008
Study Completion Date: December 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Propranolol
Drug: Propranolol
Weekly doses of short and long acting propranolol following recollection of traumatic memory
Placebo Comparator: Arm 2
Placebo
Drug: Placebo
Weekly doses of placebo following recollection of traumatic memory

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

OEF/OIF veteran diagnosed with combat related posttraumatic stress disorder

Exclusion Criteria:

  1. Not diagnosed with current, chronic PTSD
  2. Current PTSD related to a traumatic event other than the event being treated
  3. Age>65.
  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 necessary;
  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 participation.
  13. Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation.
  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 ClinicalTrials.gov identifier: NCT00645450

Locations
United States, New Hampshire
VA Medical Center, Manchester
Manchester, New Hampshire, United States, 03104
Sponsors and Collaborators
Investigators
Principal Investigator: Scott P Orr, PhD VA Medical Center, Manchester
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00645450     History of Changes
Other Study ID Numbers: MHBA-013-07S
Study First Received: March 19, 2008
Last Updated: November 19, 2013
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Stress
Posttraumatic
PTSD
Propranolol
Treatment

Additional relevant MeSH terms:
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Propranolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 21, 2014