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Emotional Memory Reactivation in Posttraumatic Stress Disorder

Information source: Assistance Publique - H˘pitaux de Paris
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Posttraumatic Stress Disorder

Intervention: AVLOCARDYL (Drug); Placebo (Drug); AVLOCARDYL (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Assistance Publique - H˘pitaux de Paris

Official(s) and/or principal investigator(s):
Charles-Siegfried Peretti, MD, PhD, Principal Investigator, Affiliation: Saint-Antoine hospital, Psychiatry unit, ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS

Overall contact:
Charles-Siegfried Peretti, MD,PhD, Phone: +33(0)1 49 28 26 35, Email: chsperetti@gmail.com

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Effect of propanolol, a beta adrenergic antagonism, on amygdala activation during a symptom provocation state in traumatized subjects with and without posttraumatic stress disorder

Secondary outcome:

Comparison of propranolol therapeutic effects versus placebo on symptom provocation state in traumatized subjects with and without posttraumatic stress disorder

Comparison of activated neuronal networks when a patient remember a pleasant , unpleasant or traumatic event

Comparison of emotional status of 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.

Eligibility

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

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

Locations and Contacts

Charles-Siegfried Peretti, MD,PhD, Phone: +33(0)1 49 28 26 35, Email: chsperetti@gmail.com

Saint-Antoine Hospital, Psychiatriy unit, Paris, Ile de France 75012, France; Recruiting
Charles-Siegfied Peretti, MD, PhD, Phone: +33(0)1 49 28 26 35, Email: chsperetti@gmail.com
Charles-Siegfried Peretti, MD, PHD, Principal Investigator
Additional Information

Related publications:

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Blanchard EB, Hickling EJ, Taylor AE, Forneris CA, Loos W, Jaccard J. Effects of varying scoring rules of the Clinician-Administered PTSD Scale (CAPS) for the diagnosis of post-traumatic stress disorder in motor vehicle accident victims. Behav Res Ther. 1995 May;33(4):471-5.

Botreau F, El Massioui N, Ch├ęruel F, Gisquet-Verrier P. Effects of medial prefrontal cortex and dorsal striatum lesions on retrieval processes in rats. Neuroscience. 2004;129(3):539-53.

Boujabit M, Bontempi B, Destrade C, Gisquet-Verrier P. Exposure to a retrieval cue in rats induces changes in regional brain glucose metabolism in the amygdala and other related brain structures. Neurobiol Learn Mem. 2003 Jan;79(1):57-71.

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. Epub 2007 Jun 22.

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Strange BA, Dolan RJ. Beta-adrenergic modulation of emotional memory-evoked human amygdala and hippocampal responses. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11454-8. Epub 2004 Jul 21.

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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. Erratum in: Biol Psychiatry. 2003 Dec 15;54(12):1471.

van Stegeren AH, Everaerd W, Cahill L, McGaugh JL, Gooren LJ. Memory for emotional events: differential effects of centrally versus peripherally acting beta-blocking agents. Psychopharmacology (Berl). 1998 Aug;138(3-4):305-10.

van Stegeren AH, Goekoop R, Everaerd W, Scheltens P, Barkhof F, Kuijer JP, Rombouts SA. Noradrenaline mediates amygdala activation in men and women during encoding of emotional material. Neuroimage. 2005 Feb 1;24(3):898-909.

Starting date: September 2010
Last updated: December 2, 2011

Page last updated: December 08, 2011

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