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The Trauma of Betrayal: Treating Adjustment Disorder With Reconsolidation Blockade Under Propranolol

Primary Purpose

Adjustment Disorders, Posttraumatic Stress Disorder, Trauma and Stressor Related Disorders

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Propranolol Pill

About this trial

This is an interventional treatment trial for Adjustment Disorders focused on measuring Reconsolidation, Propranolol, Infidelity, Attachment injury, Romantic relationships

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of an adjustment disorder or chronic adjustment disorder, as defined by the Diagnostic and Statistical Manual for Mental Disorders, as a result of an attachment injury, defined as an event involving the perceived betrayal, violation of trust, or abandonment by a significant other.
Currently experiencing clinically important psychological distress as a result of the event, as defined by a score of at least 22 on the IES-R, and a score of at least "moderately ill" on the Clinical Global Impressions - Severity of Illness Scale.
Must have been in the romantic relationship for at least 6 months prior to the event.
Must not take psychotropic medication.
Fluency in English or French

Exclusion Criteria:

Systolic blood pressure <100 mm Hg;
Cardiac rhythm below 55 beats per minute;
A medical condition that contraindicates the administration of propranolol, e.g., Asthma, chronic obstructive pulmonary disease, cardiac insufficiency, cardiac choc, Second- or third-degree atrioventricular block, diabetes, spastic angina, auricular sinus illness, bradycardia, Raynaud's disease, severe peripheral vascular disease, untreated Pheochromocytoma, arterial hypotension, previous anaphylactic allergic shock;
Previous adverse reaction to, or non-compliance with, beta-blocker;
Current use of a substance that may involve potentially dangerous interactions with propranolol, including P450 2D6 inhibitors.
Women who are pregnant or breast feeding;
Individuals currently participating in any other form of psychotherapy (other than strictly supportive).
History of substance dependence disorder, bipolar disorder, or psychotic disorder;
Participants judged (based on history, mental status exam, clinical impression, or the Suicidal Behaviors Questionnaire as being at significant risk of suicidal behavior.
Participation in another drug trial within 30 days prior to the screening visit
Presence of any clinical condition that might interfere with the interpretation of the efficacy and safety results.

Sites / Locations

Douglas Mental Health University Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Arm Label

Propranolol pill + mismatch memory reactivation

Propranolol pill + standard memory reactivation

Waitlist

Arm Description

Prediction-error will be incorporated into each treatment sessions.

Outcomes

Primary Outcome Measures

Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Impact of Events Scale-Revised

Severity of Trauma and Stressor-related symptoms

Secondary Outcome Measures

Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Hopkins Symptom Checklist-25

General Psychological Distress (Depression and Anxiety)

Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on World Health Organization - Quality of Life BREF

Perceived Quality of Life in 4 Domains, Psychological, Physical, Environmental, Social

Full Information

NCT ID

NCT03151681

First Posted

April 29, 2017

Last Updated

December 15, 2022

Sponsor

Douglas Mental Health University Institute

1. Study Identification

Unique Protocol Identification Number

NCT03151681

Brief Title

The Trauma of Betrayal: Treating Adjustment Disorder With Reconsolidation Blockade Under Propranolol

Official Title

Treating Adjustment Disorders Stemming From Romantic Betrayals: An Open-label Trial of Impairing Memory Reconsolidation Using Propranolol

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

November 1, 2015 (Actual)

Primary Completion Date

September 30, 2020 (Actual)

Study Completion Date

June 6, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Douglas Mental Health University Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Attachment injuries are events occurring within couple relationships that involve betrayal or abandonment by a significant other during times of need (e.g., infidelity). They can be understood as relationship traumas, which can lead to debilitating symptoms consistent with posttraumatic stress disorder (PTSD), depression, and generalized anxiety for the injured partner. Research has demonstrated that the presence of an attachment injury represents a barrier to empirically effective couple's therapy. However, disrupting memory reconsolidation with the beta-blocker propranolol has been shown to alleviate PTSD symptoms by attenuating the salience of the emotional trauma memory, representing an interesting avenue for the treatment of adjustment disorders stemming from attachment injuries. Moreover, evidence suggests that a certain degree of mismatch, or an error between what is expected/predicted to occur and what actually occurs, must be present in order for a memory to destabilize and enter the reconsolidation phase following retrieval. Here, the investigators aim to extend the conditions under which reconsolidation therapy with propranolol can be used in a clinical setting, as well as assess whether incorporating mismatch enhances treatment effects. The investigators hypothesize that, compared to a wait-list control, 4-6 sessions of memory reactivation under propranolol will significantly reduce trauma-related and general anxio-depressive symptoms, associated with an attachment injury. Moreover, the investigators hypothesize that participants randomized to the mismatch group will improve significantly more than the standard treatment group on all variables of interest.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adjustment Disorders, Posttraumatic Stress Disorder, Trauma and Stressor Related Disorders

Keywords

Reconsolidation, Propranolol, Infidelity, Attachment injury, Romantic relationships

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Experiment 1: Repeated measures open-label clinical trial with time-series analysis. Experiment 2: Randomized clinical trial (mismatch vs. no mismatch) with within-group wait-list.

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Randomization to 'mismatch group' or 'no-mismatch group' will be done prior to the first treatment session by a third party unrelated to the study, and blind to participant outcome. Participants will also be blind to which group they are randomized to. The randomization scheme will use the permuted-block method with a block size of four, stratified by gender (male and female) and event type (infidelity and other), and a group allocation probability of 50% (Fleiss, 1986).

Allocation

Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Propranolol pill + mismatch memory reactivation

Arm Type

Experimental

Arm Description

Prediction-error will be incorporated into each treatment sessions.

Arm Title

Propranolol pill + standard memory reactivation

Arm Type

Experimental

Arm Title

Waitlist

Arm Type

No Intervention

Intervention Type

Drug

Intervention Name(s)

Propranolol Pill

Other Intervention Name(s)

Inderal

Intervention Description

1mg/kg of propranolol 60 minutes prior to memory reactivation

Primary Outcome Measure Information:

Title

Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Impact of Events Scale-Revised

Description

Severity of Trauma and Stressor-related symptoms

Time Frame

Administered at baseline (Week 0), Post-Wait-list (Week 4), at each subsequent weekly visit, at the one-week post-treatment follow-up, and at the three-month follow up.

Secondary Outcome Measure Information:

Title

Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Hopkins Symptom Checklist-25

Description

General Psychological Distress (Depression and Anxiety)

Time Frame

Administered at baseline (Week 0), Post-Wait-list (Week 4), at each subsequent weekly visit, at the one-week post-treatment follow-up, and at the three-month follow up.

Title

Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on World Health Organization - Quality of Life BREF

Description

Perceived Quality of Life in 4 Domains, Psychological, Physical, Environmental, Social

Time Frame

Administered at baseline (Week 0), Post-Wait-list (Week 4), at the one-week post-treatment follow-up, and at the three-month follow up.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of an adjustment disorder or chronic adjustment disorder, as defined by the Diagnostic and Statistical Manual for Mental Disorders, as a result of an attachment injury, defined as an event involving the perceived betrayal, violation of trust, or abandonment by a significant other. Currently experiencing clinically important psychological distress as a result of the event, as defined by a score of at least 22 on the IES-R, and a score of at least "moderately ill" on the Clinical Global Impressions - Severity of Illness Scale. Must have been in the romantic relationship for at least 6 months prior to the event. Must not take psychotropic medication. Fluency in English or French Exclusion Criteria: Systolic blood pressure <100 mm Hg; Cardiac rhythm below 55 beats per minute; A medical condition that contraindicates the administration of propranolol, e.g., Asthma, chronic obstructive pulmonary disease, cardiac insufficiency, cardiac choc, Second- or third-degree atrioventricular block, diabetes, spastic angina, auricular sinus illness, bradycardia, Raynaud's disease, severe peripheral vascular disease, untreated Pheochromocytoma, arterial hypotension, previous anaphylactic allergic shock; Previous adverse reaction to, or non-compliance with, beta-blocker; Current use of a substance that may involve potentially dangerous interactions with propranolol, including P450 2D6 inhibitors. Women who are pregnant or breast feeding; Individuals currently participating in any other form of psychotherapy (other than strictly supportive). History of substance dependence disorder, bipolar disorder, or psychotic disorder; Participants judged (based on history, mental status exam, clinical impression, or the Suicidal Behaviors Questionnaire as being at significant risk of suicidal behavior. Participation in another drug trial within 30 days prior to the screening visit Presence of any clinical condition that might interfere with the interpretation of the efficacy and safety results.

Facility Information:

Facility Name

Douglas Mental Health University Institute

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H4H1R3

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

36031005

Citation

Lonergan M, Saumier D, Pigeon S, Etienne PE, Brunet A. Treatment of adjustment disorder stemming from romantic betrayal using memory reactivation under propranolol: A open-label interrupted time series trial. J Affect Disord. 2022 Nov 15;317:98-106. doi: 10.1016/j.jad.2022.08.082. Epub 2022 Aug 27.

Results Reference

result

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The Trauma of Betrayal: Treating Adjustment Disorder With Reconsolidation Blockade Under Propranolol

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