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

NCT01127568 | Unknown Phase 2 DMC

• 2 other identifiers: 05/25DoD, Award #: W81XWH-08-2-0126
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stress Disorders, Post-Traumatic

Keywords

Post-Traumatic Stress Disorders; Posttraumatic Stress Disorders; PTSD; Stress Disorder, Post Traumatic; Stress Disorders, Posttraumatic; Chronic Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (3)

• Clinician-Administered PTSD Scale (CAPS) for DSM-IV

  Each participant will be administered the following structured diagnostic interview instruments by a doctoral-level clinician: Clinician-Administered PTSD Scale (CAPS). The CAPS is widely regarded as the state-of-the-art structured clinical interview instrument for PTSD. It yields a categorical (present/absent) score according to DSM-IV PTSD criteria as well as severity scores for each of the 17 DSM-IV PTSD symptoms, for each of the three PTSD symptom clusters (re-experiencing, avoidance, hyperarousal) and for total PTSD.

  Session of Week 0

• Clinician-Administered PTSD Scale (CAPS) for DSM-IV

  Each participant will be administered the following structured diagnostic interview instruments by a doctoral-level clinician: Clinician-Administered PTSD Scale (CAPS). The CAPS is widely regarded as the state-of-the-art structured clinical interview instrument for PTSD. It yields a categorical (present/absent) score according to DSM-IV PTSD criteria as well as severity scores for each of the 17 DSM-IV PTSD symptoms, for each of the three PTSD symptom clusters (re-experiencing, avoidance, hyperarousal) and for total PTSD.

  Session of Week 7

• Clinician-Administered PTSD Scale (CAPS) for DSM-IV

  Each participant will be administered the following structured diagnostic interview instruments by a doctoral-level clinician: Clinician-Administered PTSD Scale (CAPS). The CAPS is widely regarded as the state-of-the-art structured clinical interview instrument for PTSD. It yields a categorical (present/absent) score according to DSM-IV PTSD criteria as well as severity scores for each of the 17 DSM-IV PTSD symptoms, for each of the three PTSD symptom clusters (re-experiencing, avoidance, hyperarousal) and for total PTSD.

  Session of Week 26

Secondary Outcomes (14)

• Mini International Neuropsychiatric Interview (MINI)

  Session of Week 6

• Peritraumatic Distress Inventory (PDI)

  Session of Week 0

• The Peritraumatic Dissociative Experiences Questionnaire

  Session of Week 0

• PTSD Check List (PCL) civilian version

  Session of Week 0

• Script-driven imagery psychophysiological measurement

  Session of Week 7

Study Arms (2)

Propranolol

EXPERIMENTAL

Propranolol 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.

Drug: Propranolol is available in generic form as the Wyeth product under the trade name Inderal.

Placebo

PLACEBO COMPARATOR

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

Drug: Propranolol is available in generic form as the Wyeth product under the trade name Inderal.

Interventions

Propranolol is available in generic form as the Wyeth product under the trade name Inderal. DRUG

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.

Placebo; Propranolol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Being between the ages of 18-65
• Having gone through a potentially traumatic event.

You may not qualify if:

• Not suffering from chronic PTSD
• Systolic blood pressure \<100 mm Hg;
• Heart rate below 55 beats per minute;
• 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.

Sponsors & Collaborators

• Douglas Mental Health University Institute: lead
• Massachusetts General Hospital: collaborator
• Harvard University: collaborator
• McGill University: collaborator
• US Department of Veterans Affairs: collaborator

Study Sites (1)

Douglas Mental Health University Institute, McGill University

Montreal, Quebec, H4H 1R3, Canada

RECRUITING

Related Publications (2)

• 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. doi: 10.1016/j.jpsychires.2007.05.006. Epub 2007 Jun 22.

  PMID: 17588604 BACKGROUND

• Brunet A, Saumier D, Liu A, Streiner DL, Tremblay J, Pitman RK. Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial. Am J Psychiatry. 2018 May 1;175(5):427-433. doi: 10.1176/appi.ajp.2017.17050481. Epub 2018 Jan 12.

  PMID: 29325446 DERIVED

Related Links

• Info-trauma is an internet site with information, diagnosis and orientation for the victims of traumatic events and their loved ones.

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

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

Study Officials

• Alain Brunet, Ph.D.

  Douglas Mental Health University Institute, McGill University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lening A. Olivera Figueroa, Psy.D.

CONTACT

514-761-6131; lening.olivera@douglas.mcgill.ca

Nelson Azoulay, B.A.

CONTACT

514-761-6131; nelson.azoulay@douglas.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: May 21, 2010
• Study Start: February 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: June 1, 2012
• Last Updated: May 21, 2010

Record last verified: 2010-02

Locations

CA (1)