DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Emotional Memory Reactivation in Posttraumatic Stress Disorder

Information source: Assistance Publique - H˘pitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015
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: Terminated

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


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.


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


Inclusion Criteria:

- Patients of French mother language

- Right-handed patients

- Signature of the consent


- Patients whose diagnosis of PTSD according to the criteria of the DSM IV-TR is


- 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


- 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

Saint-Antoine Hospital, Psychiatriy unit, Paris, Ile de France 75012, France
Additional Information

Related publications:

Adler SA, Wilk A, Rovee-Collier C. Reinstatement versus reactivation effects on active memory in infants. J Exp Child Psychol. 2000 Feb;75(2):93-115.

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.

Dirikx T, Hermans D, Vansteenwegen D, Baeyens F, Eelen P. Reinstatement of extinguished conditioned responses and negative stimulus valence as a pathway to return of fear in humans. Learn Mem. 2004 Sep-Oct;11(5):549-54.

Ferry B, McGaugh JL. Clenbuterol administration into the basolateral amygdala post-training enhances retention in an inhibitory avoidance task. Neurobiol Learn Mem. 1999 Jul;72(1):8-12.

Giles J. Beta-blockers tackle memories of horror. Nature. 2005 Jul 28;436(7050):448-9.

Gisquet-Verrier P, Botreau F, Venero C, Sandi C. Exposure to retrieval cues improves retention performance and induces changes in ACTH and corticosterone release. Psychoneuroendocrinology. 2004 May;29(4):529-56.

Herz RS. Are odors the best cues to memory? A cross-modal comparison of associative memory stimuli. Ann N Y Acad Sci. 1998 Nov 30;855:670-4.

Maheu FS, Joober R, Beaulieu S, Lupien SJ. Differential effects of adrenergic and corticosteroid hormonal systems on human short- and long-term declarative memory for emotionally arousing material. Behav Neurosci. 2004 Apr;118(2):420-8.

Przybyslawski J, Roullet P, Sara SJ. Attenuation of emotional and nonemotional memories after their reactivation: role of beta adrenergic receptors. J Neurosci. 1999 Aug 1;19(15):6623-8.

Quirarte GL, Roozendaal B, McGaugh JL. Glucocorticoid enhancement of memory storage involves noradrenergic activation in the basolateral amygdala. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14048-53.

Sara SJ. Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Mem. 2000 Mar-Apr;7(2):73-84. Review.

Simson PE, Naylor JC, Gibson B, Schneider AM, Levin D. Dose-sensitive excitation and inhibition of spontaneous amygdala activity by propranolol. Pharmacol Biochem Behav. 2001 May-Jun;69(1-2):85-92.

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.

Taylor F, Cahill L. Propranolol for reemergent posttraumatic stress disorder following an event of retraumatization: a case study. J Trauma Stress. 2002 Oct;15(5):433-7.

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: July 25, 2012

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017