Treatment of PTSD by Reduction of Traumatic Memory Reconsolidation by Propranolol : a Multisite Trial

NCT ID: NCT01713556

Last Updated: 2020-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2017-06-30

Brief Summary

The purpose of this study is to test whether propranolol, when given during a re-evocation of a traumatic memory, is capable of reducing subsequent PTSD symptoms associated with that memory.

Detailed Description

Post-traumatic stress disorder (PTSD) develops following an exposure to a life threatening event. One of the characteristic features of PTSD is the recurrence of intrusive memories of an experienced trauma. The persistence of disturbing traumatic memories in PTSD is often explained in terms of a trauma-induced enhancement of memory encoding. Several studies indicate that an increased noradrenergic activity during trauma enhances the encoding of memory. Elevated levels of norepinephrine in the cerebrospinal fluid of individuals with PTSD and the correlation of this elevation with the severity of PTSD symptoms suggest that increased noradrenergic activity is also involved in the maintenance of PTSD symptoms. Reactivation of memory by retrieval also renders the memory labile and susceptible to treatments. This latter process is referred to as memory reconsolidation. Consolidation and reconsolidation both occur within a distinct time window following new learning (in consolidation) and/or retrieval (in reconsolidation). Even well-consolidated old fear memories undergo reconsolidation and may be disrupted by means of pharmacological manipulation. Propranolol may be effective in treating PTSD long after symptoms have been consolidated. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event.

HYPOTHESE: Subjects with chronic PTSD who receive propranolol before trauma evocation will subsequently show decreased PTSD symptoms, compared to subjects who receive a placebo.

METHOD: 56 participants with chronic PTSD will be recruited for participation. On Week 1, the subjects will complete a standardized measure of PTSD symptoms. Next, 90 minutes after the administration of the study medication (either propranolol or placebo), participants will undergo a script preparation procedure, during which they will disclose details of their traumatic event. Scripts portraying this event will be prepared for subsequent replay.

On Week 2, after the administration of the study medication (either propranolol or placebo), participants will be asked (reading the script) to engaged in a script-driven mental imagery of the traumatic event. Following this procedure, PTSD symptoms will be assessed.

The same procedure will be repeated on Weeks 3, 4, 5 and 6. On Weeks 7 and 18, the standardized measure of PTSD symptoms will be repeated.

Conditions

Post-traumatic Stress Disorder

Keywords

PTSD, Propranolol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Propranolol + reactivation

they have a script-driven mental imagery of the traumatic event white drug

Group Type: EXPERIMENTAL

Propranolol

Intervention Type: DRUG

Trauma reactivation

Intervention Type: OTHER

Trauma reactivation: script-driven mental imagery of the traumatic event

Placebo + reactivation

They have a script-driven mental imagery of the traumatic event with placebo

Group Type: PLACEBO_COMPARATOR

Trauma reactivation

Intervention Type: OTHER

Trauma reactivation: script-driven mental imagery of the traumatic event

placebo

Intervention Type: DRUG

Interventions

Propranolol

Intervention Type: DRUG

Trauma reactivation

Trauma reactivation: script-driven mental imagery of the traumatic event

Intervention Type: OTHER

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of chronic PTSD
• PTSD CheckList total score >44

Exclusion Criteria

• Systolic blood pressure < 100 mmHg
• Contraindication to Propranolol
• Previous adverse reaction to a β-blocker
• Use of another β-blocker
• Use of medication that could involve potentially dangerous interactions with propranolol
• Psychotherapy or treatment with any pharmacologic PTSD medication within the 2 weeks prior to inclusion (6 weeks for fluoxetine)
• Female with reproductive potential without reliable means of contraception
• Pregnancy or lactation
• Alcohol or drug abuse

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe BIRMES, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Centre Hospitalier Charles Perrens

Bordeaux, , France

Chru Lille

Lille, , France

Chu Montpellier

Montpellier, , France

CHU Toulouse

Toulouse, , France

Countries

France

References

Roullet P, Vaiva G, Very E, Bourcier A, Yrondi A, Dupuch L, Lamy P, Thalamas C, Jasse L, El Hage W, Birmes P. Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial. Neuropsychopharmacology. 2021 Aug;46(9):1643-1649. doi: 10.1038/s41386-021-00984-w. Epub 2021 Feb 21.

Reference Type: DERIVED

PMID: 33612830 (View on PubMed)

Other Identifiers

09 106 01

Identifier Type: -

Identifier Source: org_study_id