Using Reconsolidation Blockade to Treat Trauma Related Disorders After Paris Attacks: an Effectiveness Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Using Reconsolidation Blockade to Treat Trauma Related Disorders After Paris Attacks: an Effectiveness Study

Conditions
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Post-traumatic Stress Disorder

Intervention / Treatment
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* Drug: β-adrenergic blocker propranolol
* Behavioral: Treatment as usual


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reconsolidation blockade<br>β-adrenergic blocker propranolol 1 mg / kg to each of the 6 treatment sessions | Drug: β-adrenergic blocker propranolol<br> <br> |
| Active Comparator: Treatment as usual<br>Treatment as usual like SSRIs, psychotherapy, ... | Behavioral: Treatment as usual<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The PTSD Checklist (PCL-S) | The PCL-S is a 17-item self-report scale assessing DSM-IV-TR PTSD symptoms in the past week from the perspective of the patient. The PSL-S range between 17 (no symptom) and 85 (maximum score) | change from baseline to 12 months follow-up | 
| Medical resources use | Costs, in Euros, related to healthcare utilization and work status are evaluated with the MEDico-Economic Questionnaire (MEDEC) adapted from the Client Service Receipt Inventory in order to meet the specificity of the French Health system | from baseline to 12 months follow-up | 
| Quality of life assessed by EQ-5D-5L Euroquol questionnaire | The EQ-5D-5L assesses five health dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is rated on five levels of severity. The levels of severity for each dimension ranges from no problems (1) to extreme problems/unable to perform (0) | at 12- months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD, Trauma related disorders, Reconsolidation blockade, Paris attacks