Propranolol Treatment of Traumatic Memories (PTTM) (PTTM)

This study will compare the responses of subjects with traumatic memories of varying vintages to either propranolol or placebo in a double-blind setting. It is hypothesized that those subjects who receive propranolol will experience less emotional distress when the memory is subsequently reactivated and less spontaneous re-experiences.

Study Overview

• Status: Unknown
• Conditions: Posttraumatic Stress Disorder; Traumatic Memory
• Intervention / Treatment: Drug: Propranolol Hydrochloride; Drug: Placebo

Detailed Description

Traumatic memories are responsible for significant emotional distress and disability. They are a cardinal feature of Posttraumatic Stress Disorder (PTSD). Re-experiencing the original traumatic event in a number of different ways (e.g. nightmares, intrusive recollections and dissociative flashbacks) is accompanied by distressing symptoms. The reconsolidation theory of memory proposes that when long-term memories are reactivated, they remain labile for several hours before conversion back to long-term memory. During this period they are susceptible to amnestic agents, like propranolol.

Propranolol Hydrochloride will be compared to placebo in subjects who have emotional distress associated with re-experiences of traumatic events, whether in the context of PTSD or not. Two doses of propranolol or two doses of placebo will be given at the first visit.

The objective of the trial is to determine the effectiveness of brief treatment with propranolol on subjects with traumatic memories and associated symptoms. The research hypothesis is that propranolol will be more effective than placebo, as determined by the measures used, and that this positive outcome will support the reconsolidation theory of memory.

The subjects will undergo clinician rated assessments/scales to determine the presence of pre-treatment mental disorders. Subjects will complete self-rating measures/scales to determine the impact of the traumatic experience. Blood pressure and pulse rates will also be recorded.

Post-treatment outcomes using the same instruments to determine changes at four weeks will be recorded. The differences will be compared and subjected to statistical analysis.

There is an optional component of the study for subjects allocated to the placebo group. At the end of the study, these subjects will be given the opportunity of taking two doses of propranolol and attending a single follow-up session four weeks later for a further interview, rating scale and questionnaire completion. This will provide the subjects who were on placebo an opportunity of possibly benefiting from the active treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 2M5
      • Recruiting
      • Knox Manse
      • Contact: Robin Menzies, MBBS FRCPsych (UK) FRCP (C); Phone Number: 306-668-0505; Email: knox@sasktel.net
      • Principal Investigator: Robin Menzies, MBBS FRCPsych (UK) FRCP (C)
      • Sub-Investigator: Tamara Hinz, MD
      • Sub-Investigator: Mansfield Mela, MD
      • Sub-Investigator: Curtis Chicoine, MD
      • Sub-Investigator: Hyun Lim, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female adults between 18 and 70 years of age
• A traumatic memory, as an isolated symptom or in the context of Post-traumatic Stress Disorder

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Current treatment with either a beta-blocker or a corticosteroid medicine
• Medical contraindications, as outlined in the Compendium of Pharmaceutical and Specialties and the Product Monograph
• Subjects who want to retain every aspect of their memory for the traumatic event, as some memory could be lost

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Propranolol; The protocol of the study requires that two doses of propranolol (regular propranolol 40 mg followed two hours later by long-acting propranolol 60 mg) be given at the first visit, to be taken within one hour of the reactivation of the traumatic memory. Half of the subjects (33) will be randomized to receive propranolol.	Drug: Propranolol Hydrochloride; The protocol of the study requires that two doses of propranolol (regular propranolol 40 mg followed two hours later by long-acting propranolol 60 mg) or placebo be given at the first visit, to be taken within one hour of the reactivation of the traumatic memory. Subjects will be randomized in a 1:1 ratio to either Propranolol treatment or placebo.; Other Names: APO-PROPRANOLOL (DIN 00402753); INDERAL LA (DIN 02042231); PROPRANOLOL; PROPRANOLOL LONG-ACTING
PLACEBO_COMPARATOR: Placebo; The protocol of the study requires that two doses of placebo be given at the first visit, to be taken within one hour of the reactivation of the traumatic memory. Half of the subjects (33) will be randomized to receive placebo.	Drug: Placebo; The protocol of the study requires that two doses of placebo be given at the first visit, to be taken within one hour of the reactivation of the traumatic memory. Half of the subjects (33) will be randomized to receive placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint will be changes between the pretreatment and posttreatment scores in the Clinician Assessment Posttraumatic Scale (CAPS), Impact of Event Scale (IES) and Traumatic Memory Description Measure (TMDM) instruments.	Visit 2 (Week 4)

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary endpoint will be changes between the treatment and posttreatment score in the other scales used - MINI, ZAS, ZDS and NIHS.	Visit 2 (Week 4)

Collaborators and Investigators

• Sponsor: Mela, Mansfield, M.D.
• Investigators: Principal Investigator: Robin Menzies, MBBS FRCPsych (UK) FRCP (C)

Publications and helpful links

General Publications

• Nader K, Schafe GE, Le Doux JE. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature. 2000 Aug 17;406(6797):722-6. doi: 10.1038/35021052.
• 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.
• Pitman RK. Post-traumatic stress disorder, hormones, and memory. Biol Psychiatry. 1989 Jul;26(3):221-3. doi: 10.1016/0006-3223(89)90033-4. No abstract available.
• Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002 Jan 15;51(2):189-92. doi: 10.1016/s0006-3223(01)01279-3.
• Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry. 2003 Nov 1;54(9):947-9. doi: 10.1016/s0006-3223(03)00412-8. Erratum In: Biol Psychiatry. 2003 Dec 15;54(12):1471.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ANTICIPATED): September 1, 2011
• Study Completion (ANTICIPATED): September 1, 2011

Study Registration Dates

• First Submitted: February 13, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (ESTIMATE): February 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): June 21, 2011
• Last Update Submitted That Met QC Criteria: June 19, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: PTSD; Posttraumatic Stress Disorder; Traumatic memory; Traumatic memories; Traumatic memories and associated symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: 505-2010