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

NCT04982211 | Unknown Phase 2 DMC

• 1 other identifier: PRPL-008
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Trauma and Stressor Related Disorders; Post Traumatic Stress Disorder; Acute Stress Disorder; Adjustment Disorders

Keywords

Memory Reconsolidation; Propranolol; Military personnel; Veterans; Mismatch; Efficacy

Outcome Measures

Primary Outcomes (1)

• Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores

  Change from baseline (week 0) to week 7 in PCL-5 scores

  Questionnaire administered at weeks 0 and 7

Secondary Outcomes (8)

• Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores

  Questionnaire administered at weeks 0, 1, 2, 3, 4, 5, 6, 13 and 26

• Beck Depression Inventory (BDI) scores

  Questionnaire administered at weeks 0, 1, 2, 3, 4 , 5, 6, 7, 13 and 26

• Clinical Global Impression-Improvement (CGI-I) scores

  Questionnaire administered at weeks 0, 7 and 26

• Mini Psychiatric Interview, version 7 (MINI-7)

  Questionnaire administered at weeks 0, 7 and 26

• Social Functioning Questionnaire (QFS)

  Questionnaire administered at weeks 0, 7, and 26

Study Arms (4)

Propranolol and standard trauma memory reactivation group

EXPERIMENTAL

Oral propranolol will be administered 60 minutes prior to writing (Treatment 1) or reading aloud a trauma narrative.

Drug: Propranolol

Placebo and standard trauma memory reactivation group

PLACEBO COMPARATOR

Oral placebo will be administered 60 minutes prior to writing (Treatment 1) or reading aloud a trauma narrative.

Drug: Placebo

Propranolol and mismatch trauma memory reactivation group

ACTIVE COMPARATOR

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

Placebo and mismatch trauma memory reactivation group

PLACEBO COMPARATOR

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

Interventions

Propranolol DRUG

Oral propranolol hydrochloride capsules, dosed per participant weight

Also known as: Teva propranolol

Propranolol and mismatch trauma memory reactivation group; Propranolol and standard trauma memory reactivation group

Placebo DRUG

Oral placebo capsules, dosed per participant weight

Also known as: Placebo capsules

Placebo and mismatch trauma memory reactivation group; Placebo and standard trauma memory reactivation group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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;

Sponsors & Collaborators

• Douglas Mental Health University Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Douglas Mental Health University Institute

Montreal, Quebec, H4H1R3, Canada

Location

Related Publications (10)

• Brunet A, Saumier D, Liu A, Streiner DL, Tremblay J, Pitman RK. Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial. Am J Psychiatry. 2018 May 1;175(5):427-433. doi: 10.1176/appi.ajp.2017.17050481. Epub 2018 Jan 12.

  PMID: 29325446 BACKGROUND

• Ecker B. Memory reconsolidation understood and misunderstood. International Journal of Neuropsychotherapy. 2015; 3(1): 2-46.

  BACKGROUND

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• Bradley R, Greene J, Russ E, Dutra L, Westen D. A multidimensional meta-analysis of psychotherapy for PTSD. Am J Psychiatry. 2005 Feb;162(2):214-27. doi: 10.1176/appi.ajp.162.2.214.

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  BACKGROUND

• Pedreira ME, Perez-Cuesta LM, Maldonado H. Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction. Learn Mem. 2004 Sep-Oct;11(5):579-85. doi: 10.1101/lm.76904.

  PMID: 15466312 BACKGROUND

MeSH Terms

Conditions

Trauma and Stressor Related Disorders; Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic, Acute; Adjustment Disorders

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Mental Disorders; Stress Disorders, Traumatic

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Alain Brunet, Ph.D.

  Douglas Mental Health University Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alain Brunet, Ph.D.

CONTACT

514-761-6131; alain.brunet@mcgill.ca

Daniel Saumier, Ph.D.

CONTACT

514-761-6131; saumierd@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In this study, the investigators, therapists, outcomes assessors, and research participants will be blind to study medication allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator and Full Professor, Department of Psychiatry, McGill University.

Model Details: This is a 2 x 2 factorial randomized controlled trial. Factor 1 is the trauma reactivation method (standard vs. mismatch trauma reactivation) and factor 2 is the study medication (propranolol vs. placebo). The design will be stratified by profession (military vs. police) and sex. After an eligibility assessment at baseline, participants meeting inclusion criteria will be randomly allocated to one of four groups with a 66.6% probability of getting enrolled in one of the two propranolol treatment groups.

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: July 29, 2021
• Study Start: August 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: July 29, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)