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Stress Disorders, Post-Traumatic | A Novel Treatment For Chronic Posttraumatic Stress Disorder (PTSD) Using Post-Reactivation Propranolol

Stress Disorders, Post-Traumatic research study

What is the primary objective of this study?

Objective: To use propranolol to treat established chronic post traumatic stress disorder (PTSD) by reducing reconsolidation of the reactivated trauma memory. Hypothesis: A series of treatments with propranolol, in comparison to placebo, will produce a significant reduction in PTSD symptom severity in participants with chronic PTSD. Study Design: This is a double-blind, placebo-controlled, randomized study. Methodology: Twenty-five participants per group with chronic PTSD will be recruited. On their first visit psychodiagnostic and psychometric evaluation will take place. In addition, script-preparation for the script-driven imagery procedure will occur. Following this, the participants will return each week for a period of 6 weeks to participate in the reactivation sessions with propranolol or placebo (participants assigned to the propranolol condition will receive propranolol throughout, and participants assigned to the placebo condition will receive placebo throughout). Two weeks later, the participants will return for a follow-up of the psychodiagnostic and psychometric evaluation, as well as psychophysiological assessment using script-driven imagery procedure. Data Analysis: A two-factor analysis of variance (ANOVA) for repeated measures will be performed on study completers. The Drug factor will have two levels: propranolol and placebo. The Time factor will have two levels: pre-treatment and post-treatment. We predict a significant Drug x Time interaction, more precisely a greater decrease in PTSD severity in the propranolol than in the placebo group. The psychophysiological data will be contrasted to a normative cutoff score for PTSD.

Who is eligible to participate?

Inclusion Criteria: - Being between the ages of 18-65 - Having gone through a potentially traumatic event. Exclusion Criteria: - Not suffering from chronic PTSD - Systolic blood pressure <100 mm Hg; - Heart rate below 55 beats per minute; - Having a 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 criterion 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 β-blocker, or c.) are currently being treated, regardless of the date of last occurrence. Cardiological consultation will be obtained as necessary; - Previous adverse reaction to, or non-compliance with, a β-blocker; - Current use of a medication that may involve potentially dangerous interactions with propranolol, including, other β-blockers, antiarrhythmics, calcium channel blockers, and potent P450 2D6 inhibitors, e.g., fluoxetine, paroxetine, miconazole, sulconazole, metoclopramide, quinidine, ticlopidine, and ritonavir. Because the protocol does not require to take large doses of propranolol on a daily basis, the decision to exclude participants will be taken by the physician on a case-by-case basis; - Pregnancy or breast feeding. Although propranolol can be used during pregnancy we will advise women not to participate in they are or become pregnant. Women breastfeeding will also be advised not to participate because propranolol has been found in human milk. That the quantity absorbed by the breast feeding infant is inferior to 1% of the therapeutic dose (Vidal, 2008). - Contraindicating psychiatric condition, including current psychotic, bipolar, melancholic, or substance dependence or abuse disorder; suicidality; - Initiation of, or change in, psychotropic medication within the previous 2 months. For participants 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 with regard to retaining the participant or terminating participation; - Current participation in any psychotherapy (other than strictly supportive). Participants 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 with regard to retaining the participant or terminating participation; - Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation; - Understanding neither French nor English.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Stress Disorders, Post-Traumatic

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Propranolol is available in generic form as the Wyeth product under the trade name Inderal.The study medication will consist of a dose of 2/3 mg/Kg of short-acting propranolol or placebo, followed 2 hours later by a dose of 1 mg/Kg of long-acting or placebo. The medication will be prescribed by the clinic's physician after medical check-up. A nurse will monitor blood pressure. According to, 40 mg of short-acting propranolol dose should produce a peak blood level of approximately 25 ng/ml at 2 hours, which the additional 60 mg long-acting propranolol should further increase by no more than 5ng. The decay of the blood level induced by the 40 mg short-acting dose after its 2-hour peak will outstrip the further rise induced by the 60 mg long-acting proposal dose, so that blood levels will not rise above this peak 30 ng/ml, which is within the therapeutic clinical range. If the participant tolerates the combination dose without any difficulty, during subsequent sessions, both the short- and long-acting doses will be given together immediately after memory reactivation.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

PropranololPropranolol is a beta-blocker (blocking beta- adrenergic receptors) that reduces sympathetic activity. It is a well-known drug typically prescribed to individuals suffering from hypertension, tachycardia, cardiac arrhythmia, tremors, thyroid disease, or migraine.

PlaceboThe placebo is an inactive capsule that will have no medication effect, but looks exactly like the medication.

Study Status

Unknown status

Start Date: February 2010

Completed Date: June 2012

Phase: Phase 2/Phase 3

Type: Interventional

Design:

Primary Outcome: Clinician-Administered PTSD Scale (CAPS) for DSM-IV

Secondary Outcome: Mini International Neuropsychiatric Interview (MINI)

Study sponsors, principal investigator, and references

Principal Investigator: Alain Brunet, Ph.D.

Lead Sponsor: Douglas Mental Health University Institute

Collaborator: Massachusetts General Hospital

More information:https://clinicaltrials.gov/show/NCT01127568

Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK. Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res. 2008 May;42(6):503-6. Epub 2007 Jun 22.

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