The investigators propose to examine a mismatch-based method of reconsolidation blockade for the treatment of psychological trauma in military personnel and Federal police officers. The standard reconsolidation blockade treatment (aka Reconsolidation Therapy) involves reactivating the trauma memory while under the influence of propranolol. The mismatch method of Reconsolidation Therapy will involve varying the contexts in which the weekly trauma memory retrieval will occur. This study will involve 10 visits (eligibility assessment, treatments, and follow-up visits) over a 6-month period for each participant. Treatments will be conducted once a week for a six-week period where the participant will take a dose of propranolol (or a placebo pill) 60 minutes prior to memory reactivation. The investigators hypothesize that reconsolidation blockade treatment will be as effective in treating PTSD among military personnel and Federal police officers, with the mismatch condition showing greater symptom improvement.

Traumatic stress remains a treatment-refractory mental health problem characterized by symptoms of re-experiencing, avoidance, negative cognitions and affect, and hyperarousal. Due to the nature of their profession, military personnel and the Federal police officers (RCMP; Royal Canadian Mounted Police) are at a greater risk of suffering from traumatic stress. Thus, there is an important unmet need for developing novel treatments for trauma-related disorders, particularly for the military and RCMP.

Considering the pivotal role of negative emotional experiences in the development and persistence of PTSD, blocking the reconsolidation of such experiences opens the door to a novel and powerful treatment approach against this disorder. We (Brunet et al, 2018) have previously shown the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker, in reducing symptoms of post-traumatic stress disorder (PTSD). Although this therapeutic method was shown to be efficacious, it is hypothesized that symptomatic improvements may be increased by including a mismatch experience between what is expected during memory recall and the actual recall experience, in line with mismatch theory (Pedreira et al, 2004; see Ecker, 2015). In this study, we test the effects of a mismatch procedure by altering the context in which the trauma memory retrieval occurs. Standard and mismatch reconsolidation therapy procedures will be used to treat PTSD in military personnel and Federal police officers.

Primary objective:

• Compare the effects of Standard Reconsolidation Therapy using propranolol vs. placebo on PTSD symptoms one-week post-treatment.

Primary hypothesis:

It is predicted that propranolol administration will yield greater PTSD symptom improvement than placebo at one week following the last treatment visit.

Secondary objectives:

• Compare the effect of Standard vs. Mismatch Reconsolidation Treatment conditions on PTSD symptoms using propranolol during treatment, one-week post-treatment and at six months;
• Determine whether Reconsolidation Therapy with propranolol is associated with greater PTSD symptom reductions than placebo during treatment and at six months;
• Examine the proportion of participants rated as 'improved' based on a global clinical impression rating scale across treatment conditions;
• Examine the proportion of participants who no longer meet PTSD diagnostic criteria at one-week post-treatment and follow-up according to treatment condition;
• Explore the effect of the treatment on depressive symptoms, dissociative symptoms, complex PTSD symptomatology, and quality of life;
• Examine the effect of treatment condition on drop-outs and relapse rates;

Procedures

To accomplish the study objectives, the investigators will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at each treatment visit, as well as at one-week, 3-month and 6-month post-treatment visits). At each treatment session, participants will be asked recall their traumatic memory with the help of a trauma narrative under the influence of propranolol or a placebo. Recall will occur using a standard reconsolidation or mismatch protocol. Four treatment conditions will be defined, as follows:

• Group 1: Standard trauma memory reactivation + propranolol;
• Group 2: Standard trauma reactivation + placebo;
• Group 3: Modified trauma reactivation + propranolol;
• Group 4: Modified trauma reactivation + placebo.

As a means to favor recruitment, the current study will use an unbalanced sampling design. We will randomize 50 participants per cell in each of two active treatment groups and 25 participants per cell in the two placebo groups. Approximately 4 sites will be involved in recruiting participants for the study: one in the US, with the remaining sites in Canada. We are targeting 150 study participants with the aim of obtaining 121 treatment completers, taking into account an approximate 20% attrition rate.

The protocol will involve 10 study visits over a 6-month period. The first two visits will serve to obtain consent, establish the PTSD diagnosis, and determine eligibility. Treatments will occur once a week for 6 weeks. The standard reconsolidation therapy procedure will involve having participants write or read a summary of their traumatic experience under the influence of propranolol. The mismatch reconsolidation therapy condition will involve changing the way the trauma narrative is used to reactivate the trauma memory at each visit . Participants will not be informed in advance of the mismatch procedures. Follow-up assessments for all participants will be conducted one week post-treatment, as well as at three- and six-months after study entry.

Statistical Analyses. It is hypothesized that both standard and mismatch therapy conditions under propranolol will show greater improvements than with placebo. However, it is the mismatch therapy condition using propranolol is expected to yield significantly greater improvements in PTSD symptoms relative to the other three conditions. All data will be tested using mixed effects statistical models.

Inclusion Criteria:

(i) Male or female 18-65 years old;

(ii) Individuals who are either:

• Employed full-time as part of the Canadian or US military forces or the RCMP;
• On leave of absence from Canadian or US military forces, or the RCMP;
• Veterans of the Canadian or US military forces or the RCMP;

(iii) Evidence of a personally signed and dated informed consent form;

(iv) Individuals suffering from occupationally related PTSD, as defined by the DSM-5, for 6 consecutive months or more.

(v) Females of childbearing potential willing to use contraception for the duration of the treatment period of the study.

Exclusion Criteria:

(i) Basal systolic blood pressure < 100 mm Hg;

(ii) Basal heart rate < 50 BPM;

(iii) Medical conditions contraindicating the administration of propranolol or beta blockers

(iv) A known hypersensitivity to propranolol or any of the study product or placebo ingredients;

(v) Clinically significant lactose intolerance;

(vi) Use of medication that involves unwanted interactions with propranolol including but not limited to other beta-blockers, anti-arrhythmic medications, and calcium channel blockers;

(vii) Current use of propranolol;

(viii) Pregnant or breast-feeding women;

(ix) Individuals with borderline personality, bipolar disorder, psychosis;

(x) Current DSM-5 substance dependence;

(xi) Active suicidal ideations, as demonstrated by a response of 2 or 3 on item 7 of the Beck Depression Inventory - Short Form;

(xii) A score below 'moderately ill' on the severity scale of the Clinical Global Impression scale;

(xiii) Participating in active litigation related to the traumatic event (Veterans Affairs Canada claims are permitted, excluding judicial claims);

(xiv) Strong dissociative tendencies, as evidenced by the Dissociative Experience Scale (8-item version, DES-T);

(xv) Suspected or confirmed traumatic brain injury during the last 24 months;

(xvi) Understanding neither English nor French;

(xvii) Participants who receive exposure-based cognitive-behavioral therapy during the treatment phase of the study;

(xviii) Presence of any medical condition that in the opinion of the investigator may compromise patient safety or study objectives.

In this study, the investigators, therapists, outcomes assessors, and research participants will be blind to study medication allocation.