Emotional Memory Reactivation in Posttraumatic Stress Disorder

Phase 3

Terminated

• Conditions: Posttraumatic Stress Disorder
• Interventions: Drug: Placebo; Drug: AVLOCARDYL

• Registration Number: NCT01239173
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

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 This seems to be confirmed by an as yet unpublished human based study that suggests that propranolol may impair reconsolidation of conditioned fear-response (Miller et al., 2004) The primary purpose of our study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.

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-10-25
• Study First Submitted QC: 2010-11-10
• Study First Posted: 2010-11-11
• Primary Completion: 2011-11
• Status Verified: 2012-02
• Study Completion: 2012-02
• Last Update Submitted: 2012-07-25
• Last Update Posted: 2012-07-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Post-traumatic stress disorder receiving placebo 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI
3	AVLOCARDYL	Controls receiving propanolol 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI
1	AVLOCARDYL	Post-traumatic stress disorder patient receiving propanolol 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI
4	Placebo	Controls receiving placebo 90 min before the emotional memory reactivation and the anatomical and functional exploration in fMRI

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Saint-Antoine Hospital, Psychiatriy unit; 🇫🇷 Paris, Ile de France, France