Propranolol Treatment of Traumatic Memories (PTTM) (PTTM)

• ClinicalTrials.gov Identifier: NCT01069159
• Recruitment Status: Unknown
• First Posted: February 17, 2010
• Last Update Posted: June 21, 2011
• Sponsor: Mela, Mansfield, M.D.
• Information provided by: Mela, Mansfield, M.D.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Traumatic Memory; Posttraumatic Stress Disorder	Drug: Propranolol Hydrochloride; Drug: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Propranolol Treatment of Traumatic Memories (PTTM)
• Study Start Date: February 2010
• Estimated Primary Completion Date: September 2011
• Estimated Study Completion Date: September 2011

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Visit 2 (Week 4) ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Robin Menzies, MBBS FRCPsych (UK) FRCP (C); 306-668-0505; knox@sasktel.net

Locations

Canada, Saskatchewan

Knox Manse; Recruiting

Saskatoon, Saskatchewan, Canada, S7N 2M5

Contact: Robin Menzies, MBBS FRCPsych (UK) FRCP (C) 306-668-0505 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

Sponsors and Collaborators

Mela, Mansfield, M.D.

Investigators

• Principal Investigator: Robin Menzies, MBBS FRCPsych (UK) FRCP (C)

More Information

Publications:

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.

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.

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.

• Responsible Party: Dr. Robin Menzies, Knox Manse
• ClinicalTrials.gov Identifier: NCT01069159
• Other Study ID Numbers: 505-2010
• First Posted: February 17, 2010
• Last Update Posted: June 21, 2011
• Last Verified: June 2011

Keywords provided by Mela, Mansfield, M.D.:

Traumatic memory; Traumatic memories; Traumatic memories and associated symptoms; Posttraumatic Stress Disorder; PTSD

Additional relevant MeSH terms:

Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Propranolol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents