Comparing Standard vs. Modified Reconsolidation Blockade for the Treatment of Psychological Trauma

July 23, 2021 updated by: Alain Brunet, Ph.D., Douglas Mental Health University Institute

Comparing Standard vs. Modified Reconsolidation Blockade for the Treatment of Psychological Trauma: A Randomized Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H4H1R3
        • Douglas Mental Health University Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Propranolol and standard trauma memory reactivation group
Oral propranolol will be administered 60 minutes prior to writing (Treatment 1) or reading aloud a trauma narrative.
Drug: Propranolol
Oral propranolol hydrochloride capsules, dosed per participant weight
Other Names:
  • Teva propranolol
Placebo Comparator: Placebo and standard trauma memory reactivation group
Oral placebo will be administered 60 minutes prior to writing (Treatment 1) or reading aloud a trauma narrative.
Drug: Placebo
Oral placebo capsules, dosed per participant weight
Other Names:
  • Placebo capsules
Active Comparator: Propranolol and mismatch trauma memory reactivation group
Oral propranolol will be administered 60 minutes prior to a memory reactivation procedure involving variations in the contexts where the trauma memory reactivations occur.
Drug: Propranolol
Oral propranolol hydrochloride capsules, dosed per participant weight
Other Names:
  • Teva propranolol
Placebo Comparator: Placebo and mismatch trauma memory reactivation group
Oral placebo will be administered 60 minutes prior to a memory reactivation procedure involving variations in the contexts where the trauma memory reactivations occur.
Drug: Placebo
Oral placebo capsules, dosed per participant weight
Other Names:
  • Placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores
Time Frame: Questionnaire administered at weeks 0 and 7
Change from baseline (week 0) to week 7 in PCL-5 scores
Questionnaire administered at weeks 0 and 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores
Time Frame: Questionnaire administered at weeks 0, 1, 2, 3, 4, 5, 6, 13 and 26
Changes from baseline in PCL-5 scores during treatment and at weeks 13 and 26
Questionnaire administered at weeks 0, 1, 2, 3, 4, 5, 6, 13 and 26
Beck Depression Inventory (BDI) scores
Time Frame: Questionnaire administered at weeks 0, 1, 2, 3, 4 , 5, 6, 7, 13 and 26
Changes from baseline in BDI scores during treatment and at week 26
Questionnaire administered at weeks 0, 1, 2, 3, 4 , 5, 6, 7, 13 and 26
Clinical Global Impression-Improvement (CGI-I) scores
Time Frame: Questionnaire administered at weeks 0, 7 and 26
Absolute CGI-I scores
Questionnaire administered at weeks 0, 7 and 26
Mini Psychiatric Interview, version 7 (MINI-7)
Time Frame: Questionnaire administered at weeks 0, 7 and 26
Proportion of participants who no longer meet PTSD diagnostic criteria at Weeks 7 and 26.
Questionnaire administered at weeks 0, 7 and 26
Social Functioning Questionnaire (QFS)
Time Frame: Questionnaire administered at weeks 0, 7, and 26
Changes from baseline in QFS scores
Questionnaire administered at weeks 0, 7, and 26
World Health Organization - Quality of Life BREF
Time Frame: Questionnaire administered at weeks 0, 7, and 26
Changes from baseline in World Health Organization - Quality of Life BREF scores
Questionnaire administered at weeks 0, 7, and 26
Dissociative Experiences Scale (DES-T)
Time Frame: Questionnaire administered at week 0.
Changes from baseline in DES-T scores
Questionnaire administered at week 0.
International Trauma Questionnaire (ITQ)
Time Frame: Questionnaire administered at baseline and weeks 0, 7, and 26
Changes from baseline in ITQ scores
Questionnaire administered at baseline and weeks 0, 7, and 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Douglas Mental Health University Institute

Collaborators

Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: Alain Brunet, Ph.D., Douglas Mental Health University Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

July 23, 2021

First Submitted That Met QC Criteria

July 23, 2021

First Posted (Actual)

July 29, 2021

Study Record Updates

Last Update Posted (Actual)

July 29, 2021

Last Update Submitted That Met QC Criteria

July 23, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRPL-008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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