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CompletedNCT03151681Updated Dec 19, 2022

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

A Phase 2/3 interventional study of Propranolol Pill in Adjustment Disorders, Posttraumatic Stress Disorder and Trauma and Stressor Related Disorders, sponsored by Douglas Mental Health University Institute. Completed at 1 site in Canada. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-12-19.

Sponsored by Douglas Mental Health University Institute · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
84
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

02

Conditions studied

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

Keywords

  • Reconsolidation
  • Propranolol
  • Infidelity
  • Attachment injury
  • Romantic relationships
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
84 participants (actual)

Study arms

  • Experimental
    Propranolol pill + mismatch memory reactivation

    Prediction-error will be incorporated into each treatment sessions.

    Drug: Propranolol Pill

  • Experimental
    Propranolol pill + standard memory reactivation

    Drug: Propranolol Pill

  • No intervention
    Waitlist

Interventions

  • DrugPropranolol Pill

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

    Also known as: Inderal

05

What researchers measure

Primary outcomes

  1. 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

    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 outcomes

  1. 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)

    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.

  2. 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

    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.

06

Study locations

1 site
  • Douglas Mental Health University Institute
    Montréal, Quebec H4H1R3, Canada
07

References and documents

Publications

  • 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. PubMed 36031005 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03151681
Lead sponsor
Douglas Mental Health University Institute
Responsible party
Alain Brunet, Ph.D. (Primary Investigator and Full Professor, Department of Psychiatry, McGill University., Douglas Mental Health University Institute) — Principal investigator
First posted
May 12, 2017
Start date
Nov 1, 2015
Primary completion
Sep 30, 2020
Completion
Jun 6, 2022
Last update
Dec 19, 2022

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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