Emotional Memory Reactivation in Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder. The primary purpose of our study is to assess the effect of propanolol, a beta adrenergic antagonism, on amygdala activation during a symptom provocation state in traumatized subjects with and without posttraumatic stress disorder.

Detailed Description
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Post-traumatic stress disorder (PTSD) is a type of anxiety disorder that's triggered by an extremely traumatic event. Traumatic events that may trigger PTSD include violent personal assaults, accidents, natural or human-caused disasters, or military combat. Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder. Initially based on animal studies, the idea that memory for emotional material in humans is modulated by the noradrenergic system and by the amygdala, has received a strong support over the last decade. Evidence mainly comes from studies investigating the effect of emotion on encoding processes (Mc GAUGH, 2000). In that view, propranolol has been used somewhat successfully shortly after trauma to reduce the development of PTSD symptoms (Pitman et al., 2002; VAIVA et al., 2003). As already mentioned, reconsolidation studies developed in rats provide treatment strategies that can be used long after PTSD induction. Recent evidence indicates that consolidated long-term memory in human can also be influenced by events delivered after memory reactivation (Walker et al., 2003; HUPBACH et al., 2007), suggesting that human memory can be retroactively altered by treatments delivered in conjunction with memory reactivation. This seems to be confirmed by an as yet unpublished human based study that suggests that propranolol may impair reconsolidation of conditioned fear-response (Miller et al., 2004) The primary purpose of our study is to assess the effect of propanolol, a beta adrenergic antagonism, on amygdala activation during a symptom provocation state in traumatized subjects with and without posttraumatic stress disorder. One Functional magnetic resonance imaging (fMRI) will be performed (week 1) in 32 patients with PTSD and 32 controls (exposure to a traumatic event without PTSD) to examine amygdala activation during a provocation state. One half of the patients with PTSD and one half of the controls will receive propranolol prior the fMRI under double blind condition. In addition, a cognitive test battery will be performed (screening, week 0, 1, 2) before the fRMI acquisition and at follow up visits.

Official Title
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Reliving the Traumatic Event in Posttraumatic Stress Disorder: An Emotional Memory Reactivation Pathology? An fMRI Study

Conditions
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Posttraumatic Stress Disorder

Intervention / Treatment
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* Drug: AVLOCARDYL
* Drug: Placebo
* Drug: AVLOCARDYL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of French mother language Right-handed patients Signature of the consent Patients: Patients whose diagnosis of PTSD according to the criteria of the DSM IV-TR is established PTSD whose evolution is not chronic Established PTSD : Symptoms presents for at least 1 month PTSD consecutive to a unique traumatic event Controls : The healthy controls will have sudden a traumatism of the same nature or the nature comparable to that of the patients suffering from PTSD, but they will not have developed pathology Subjects having undergone a traumatism dating less than 3 months Examples of traumatic events: aggression, accident of the public highway, the occupational accident Exclusion Criteria: The PTSD consecutive to several traumatic events Patients treated by a substance crossing the blood-brain barrier (with the exception of the antidepressants of the family of the ISRS which can be indicated in the treatment of PTSD) Histories of epilepsy or significant loss of consciousness of any origin, including post-traumatic Any psychiatric or somatic significant pathology The psychiatric histories in particular of suicide attempt The pregnant or breast-feeding women Contraindications in the propanolol Consumption of psychoactive drugs detected in urines Excessive alcohol consumption The persons not being capable of understanding or of reading the information describing the study The patients refusing to sign the form of consent of participation for the study The left-handed or ambidextrous patients The patients without the general regime of the health insurance The patients under guardianship or incapable major The patients who will not be capable of supplying a documentary evidence of identity the day of the inclusion Contraindication in the practice of a MRI The patients or the controls refusing the medical and psychiatric balance assessment of screening cannot participate in the study Strong probability of not compliance to the protocol or of abandonment in the course of study Taking of a speechless medicine, in particular beta-blocking Participating in phase of exclusion from a previous study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Post-traumatic stress disorder patient receiving propanolol 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI | Drug: AVLOCARDYL<br>* A grip of 2 tablets of 20 mg each took 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI<br>|
| Placebo Comparator: 2<br>Post-traumatic stress disorder receiving placebo 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI | Drug: Placebo<br>* A grip of 2 tablets of 20 mg each took 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI<br>|
| Active Comparator: 3<br>Controls receiving propanolol 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI | Drug: AVLOCARDYL<br>* A grip of 2 tablets of 20 mg each took 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI<br>|
| Placebo Comparator: 4<br>Controls receiving placebo 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI | Drug: Placebo<br>* A grip of 2 tablets of 20 mg each took 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of propanolol, a beta adrenergic antagonism, on amygdala activation during a symptom provocation state in traumatized subjects with and without posttraumatic stress disorder |  | 34 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of propranolol therapeutic effects versus placebo on symptom provocation state in traumatized subjects with and without posttraumatic stress disorder |  | 34 days | 
| Comparison of activated neuronal networks when a patient remember a pleasant , unpleasant or traumatic event |  | 34 days | 
| Comparison of emotional status of traumatized subjects with and without posttraumatic stress disorder |  | 34 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Posttraumatic stress disorder, functional Magnetic Resonance Imaging, Amygdala, emotion regulation, memory