Clinical trial NCT02789982: Using Reconsolidation Blockade to Treat Trauma Related Disorders After Paris Attacks: an Effectiveness Study
Official title: Using Reconsolidation Blockade to Treat Trauma Related Disorders After Paris Attacks: an Effectiveness Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-traumatic Stress Disorder
Keywords: PTSD
Trauma related disorders
Reconsolidation blockade
Paris attacks
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: MSD France
First posted: 2016-06-03
Enrollment: 364
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is: (1) to examine the effectiveness of reconsolidation blockade as a treatment for trauma-related disorders, (2) to evaluate the feasibility of implementing this new treatment on a large scale in a short delay. This clinical trial as been set up in response to the Paris attacks to increase treatment capacity of the AP-HP (Assistance Publique des Hopitaux de Paris) hospital network.. Reconsolidation blockade will be compared to treatment as usual (TAU), on symptoms reduction after 6 weeks of treatment. In order to measure effectiveness and cost-utility, socioeconomic measures, quality of life and social functioning outcomes will be measured pre- and post-treatment as well as 3 and 12 months after study enrollment.

Detailed description: The November 13th Paris attacks were the most violent and devastating events to occur in France since World War II. A large number of persons are likely to develop PTSD or trauma-related disorders, especially victims directly involved, their families, as well as the the first responders. In this context, there is an urgent need to enhance treatment resources. Psychotherapy is known to be effective but it is costly, and require qualified professionals. Pharmacotherapy (e.g., selective serotonin reuptake inhibitor,SSRIs) is also considered effective. However, side effects often lead patients to abandon their treatment. An alternative evidence-based intervention is the use of the β-adrenergic blocker propranolol used to interfere with the reconsolidation of a recalled traumatic memory, so as to reduce its strength over time. This clinical trial will evaluate the effectiveness and cost-utility of reconsolidation blockade compared to treatment as usual. The study involves four assessments: pre- and post-treatment and 13 weeks and 1 year follow up. The outcome measures include: PTSD symptoms, socioeconomic variables, quality of life and social functioning measures. The investigators hypothesize that all patients will improve. However, patients receiving reconsolidation blockade will recover faster than treatment as usual. Finally, investigators hypothesize that reconsolidation blockade will be well accepted both by the professionals and the patients.

Eligibility criteria: Inclusion Criteria:

* Age 16 years or older
* Suffer from PTSD, adjustment disorders or other specified trauma- and stressor-related disorder
* PTSD Checklist - Specific (PCL-S) \> 44
* Clinical Global Impression (CGI) \> 3
* Informed Consent Form signed
* Fluency in French

Exclusion Criteria:

Reconsolidation blockade group:

* Resting systolic blood pressure \< 100 mm Hg
* Resting heart rate \< 55 beats per minute
* EKG significantly abnormal
* Medical contraindication to use propranolol
* Current use of medication that involve potentially dangerous interactions with propranolol
* Previous adverse reaction to a β-adrenergic blocker
* Current use of a β-adrenergic blocker
* Patients taking psychotropic drugs which may interact with propranolol will be examined on a case-by-case basis

Both groups:

* Subject under legal protection
* Bipolar or psychotic disorder
* Head trauma for less than one year or with clinical symptoms and neurological sequelae
* Proven severe suicide risk (Mini-S and clinical assessment)
* Opioid addiction or current alcohol dependence
* Patients using SSRI for less than 2 months
* Absence of affiliation to National french social security system
* Pregnant or breastfeeding woman or without effective contraception

Primary outcomes:
measure: The PTSD Checklist (PCL-S)
timeFrame: change from baseline to 12 months follow-up
measure: Medical resources use
timeFrame: from baseline to 12 months follow-up
measure: Quality of life assessed by EQ-5D-5L Euroquol questionnaire
timeFrame: at 12- months follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Créteil
country: France
facility: Hôpital Albert Chenevier
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: Issy-les-Moulineaux
country: France
facility: Hôpital Corentin Celton
city: Jossigny
country: France
facility: Grand Hôpital EST FRANCILIEN - site de Marne-la-Vallée
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Lille
country: France
facility: CHRU et CIC de LILLE
city: Meaux
country: France
facility: Grand Hôpital EST FRANCILIEN - site de Meaux
city: Nice
country: France
facility: Chu Pasteur
city: Nice
country: France
facility: Centre Hospitalier Sainte Marie
city: Paris
country: France
facility: Hôpital Maison Blanche Hauteville
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Hôpital Sainte-Anne
city: Poitiers
country: France
facility: Centre Hospitalier Henri Laborit
city: Saint-Denis
country: France
facility: EPS Ville Evrard - site de Saint Denis
city: Saint-Maurice
country: France
facility: Hôpitaux de Saint Maurice
city: Sotteville-lès-Rouen
country: France
facility: Centre Hospitalier du Rouvray
city: Fort-de-France
country: Martinique
facility: Centre Hospitalier Universitaire de Martinique
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Bruno MILLET, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mallet C, Chick CF, Maatoug R, Fossati P, Brunet A, Millet B. Memory reconsolidation impairment using the beta-adrenergic receptor blocker propranolol reduces nightmare severity in patients with posttraumatic stress disorder: a preliminary study. J Clin Sleep Med. 2022 Jul 1;18(7):1847-1855. doi: 10.5664/jcsm.10010.
citation: Brunet A, Ayrolles A, Gambotti L, Maatoug R, Estellat C, Descamps M, Girault N, Kalalou K, Abgrall G, Ducrocq F, Vaiva G, Jaafari N, Krebs MO, Castaigne E, Hanafy I, Benoit M, Mouchabac S, Cabie MC, Guillin O, Hodeib F, Durand-Zaleski I, Millet B. Paris MEM: a study protocol for an effectiveness and efficiency trial on the treatment of traumatic stress in France after the 2015-16 terrorist attacks. BMC Psychiatry. 2019 Nov 8;19(1):351. doi: 10.1186/s12888-019-2283-4.