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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Douglas Mental Health University Institute.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Massachusetts General Hospital
Harvard University
McGill University
Information provided by:
Douglas Mental Health University Institute
ClinicalTrials.gov Identifier:
NCT01127568
First received: April 13, 2010
Last updated: May 20, 2010
Last verified: February 2010
  Purpose

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.


Condition Intervention Phase
Stress Disorders, Post-Traumatic
Drug: Propranolol is available in generic form as the Wyeth product under the trade name Inderal.
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Novel Treatment For Chronic Posttraumatic Stress Disorder (PTSD) Using Post-Reactivation Propranolol

Resource links provided by NLM:


Further study details as provided by Douglas Mental Health University Institute:

Primary Outcome Measures:
  • Clinician-Administered PTSD Scale (CAPS) for DSM-IV [ Time Frame: Session of Week 0 ] [ Designated as safety issue: Yes ]
    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.

  • Clinician-Administered PTSD Scale (CAPS) for DSM-IV [ Time Frame: Session of Week 7 ] [ Designated as safety issue: Yes ]
    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.

  • Clinician-Administered PTSD Scale (CAPS) for DSM-IV [ Time Frame: Session of Week 26 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Mini International Neuropsychiatric Interview (MINI) [ Time Frame: Session of Week 6 ] [ Designated as safety issue: Yes ]
    Mini International Neuropsychiatric Interview (MINI) will evaluate pre-event history and post-event development of each Axis I mental disorder that it addresses.

  • Peritraumatic Distress Inventory (PDI) [ Time Frame: Session of Week 0 ] [ Designated as safety issue: No ]
    The Peritraumatic Distress Inventory (PDI) is a validated 13-item instrument that quantifies the intensity of peritraumatic emotional distress, reflecting the DSM-IV A.2 (traumatized response) PTSD criterion.

  • The Peritraumatic Dissociative Experiences Questionnaire [ Time Frame: Session of Week 0 ] [ Designated as safety issue: No ]
    The Peritraumatic Dissociative Experiences Questionnaire26 is a validated 10-item instrument that quantifies the intensity of dissociative reactions at the time of the traumatic event.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 0 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • Script-driven imagery psychophysiological measurement [ Time Frame: Session of Week 7 ] [ Designated as safety issue: No ]
    Participant will be attached to recording electrodes to measure their psychophysiological reaction while listening to the narration of a script describing their traumatic event.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 1 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 2 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 3 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 4 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 5 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 6 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 7 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • PTSD Check List (PCL) civilian version [ Time Frame: Session of Week 26 ] [ Designated as safety issue: Yes ]
    The PTSD Check List (PCL) civilian version is a scale of 17 questions that now corresponds to the DSM IV. Respondents are asked how often they have been bothered by each symptom on the past month on a 5-point severity scale.

  • Script-driven imagery psychophysiological measurement [ Time Frame: Session of Week 26 ] [ Designated as safety issue: No ]
    Participant will be attached to recording electrodes to measure their psychophysiological reaction while listening to the narration of a script describing their traumatic event.


Estimated Enrollment: 50
Study Start Date: February 2010
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Propranolol
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.
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 Comparator: Placebo
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.
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.

  Show Detailed Description

  Eligibility

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

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.
  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: NCT01127568

Contacts
Contact: Lening A. Olivera Figueroa, Psy.D. 514-761-6131 ext 3430 lening.olivera@douglas.mcgill.ca
Contact: Nelson Azoulay, B.A. 514-761-6131 ext 3473 nelson.azoulay@douglas.mcgill.ca

Locations
Canada, Quebec
Douglas Mental Health University Institute, McGill University Recruiting
Montreal, Quebec, Canada, H4H 1R3
Principal Investigator: Alain Brunet, Ph.D.         
Sponsors and Collaborators
Douglas Mental Health University Institute
Massachusetts General Hospital
Harvard University
McGill University
Investigators
Principal Investigator: Alain Brunet, Ph.D. Douglas Mental Health University Institute, McGill University
  More Information

Additional Information:
Publications:
Responsible Party: Dr. Alain Brunet, Ph.D., Department of Psychiatry, Psychosocial Research Division, Douglas Mental Health University Institute, McGill University
ClinicalTrials.gov Identifier: NCT01127568     History of Changes
Other Study ID Numbers: 05/25, DoD, Award #: W81XWH-08-2-0126
Study First Received: April 13, 2010
Last Updated: May 20, 2010
Health Authority: Canada: Douglas Institute Research Ethics Board (McGill University, Montreal, Quebec);
United States: Partners Human Research Committee (Mass. General Hospital, Harvard University);
United States: Partners HealthCare System, Inc., (Mass. General Hospital, Harvard University);
United States: Army Medical Research and Materiel Command, Human Research Protection Office (HRPO);
United States: Food and Drug Administration

Keywords provided by Douglas Mental Health University Institute:
Post-Traumatic Stress Disorders
Posttraumatic Stress Disorders
PTSD
Stress Disorder, Post Traumatic
Stress Disorders, Posttraumatic
Chronic Post Traumatic Stress Disorder

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

ClinicalTrials.gov processed this record on July 23, 2014