Adjustment DisordersPhase 2/3NCT03151681
The Trauma of Betrayal: Treating Adjustment Disorder With Reconsolidation Blockade Under Propranolol
A Phase 2/3 study testing Propranolol Pill in people with Adjustment Disorders and Posttraumatic Stress Disorder, run by Douglas Mental Health University Institute at 1 site in Canada.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Adjustment Disorders, Posttraumatic Stress Disorder, Trauma and Stressor Related Disorders
- What is being tested?
- Propranolol Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2015to 6 Jun 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Douglas Mental Health University Institute
Montreal, Quebec, H4H1R3
About this study
Official title: Treating Adjustment Disorders Stemming From Romantic Betrayals: An Open-label Trial of Impairing Memory Reconsolidation Using Propranolol
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.
- Conditions
- Adjustment Disorders, Posttraumatic Stress Disorder, Trauma and Stressor Related Disorders
- Being tested
- Propranolol Pill
- Keywords
- Reconsolidation, Propranolol, Infidelity, Attachment injury, Romantic relationships
- Medical subject headings
- Adjustment Disorders, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propranolol PillDrug
Also called Inderal
1mg/kg of propranolol 60 minutes prior to memory reactivation
| Study group | Role | What they receive |
|---|---|---|
| Propranolol pill + mismatch memory reactivation | Experimental | Prediction-error will be incorporated into each treatment sessions. Receives: Drug: Propranolol Pill |
| Propranolol pill + standard memory reactivation | Experimental | Not described Receives: Drug: Propranolol Pill |
| Waitlist | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 (2)
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)
Measured: 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.
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
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start1 Nov 2015
- Primary completion30 Sep 2020
- Study completion6 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adjustment DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Douglas Mental Health University Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alain Brunet, Ph.D., Douglas Mental Health University Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03151681
- Sponsor's protocol ID
- PRPL-006
- Status last verified
- Dec 2022
- First submitted
- 29 Apr 2017
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating Adjustment Disorders Stemming From Romantic Betrayals: An Open-label Trial of Impairing Memory Reconsolidation Using Propranolol
- ClinicalTrials.gov ID
- NCT03151681
- Acronym / sponsor ID
- PRPL-006
- Conditions
- Adjustment Disorders, Posttraumatic Stress Disorder, Trauma and Stressor Related Disorders
- Keywords
- Reconsolidation, Propranolol, Infidelity, Attachment injury, Romantic relationships
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Douglas Mental Health University InstituteUniversity, hospital or other
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 30 Sep 2020 (actual)
- Study completion
- 6 Jun 2022 (actual)
- First posted
- 12 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Propranolol pill + mismatch memory reactivation | Experimental | Drug: Propranolol PillPrediction-error will be incorporated into each treatment sessions. |
| Propranolol pill + standard memory reactivation | Experimental | Drug: Propranolol Pill |
| Waitlist | No intervention | – |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propranolol PillAlso: Inderal1mg/kg of propranolol 60 minutes prior to memory reactivation | Drug | Propranolol pill + mismatch memory reactivation, Propranolol pill + standard memory reactivation |
Primary outcome
Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Impact of Events Scale-Revised
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.
Severity of Trauma and Stressor-related symptoms
2 secondary outcomes
Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Hopkins Symptom Checklist-25
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.
Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on World Health Organization - Quality of Life BREF
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
- Results publication: PubMed 36031005Lonergan 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Propranolol Pill in people with Adjustment Disorders and Posttraumatic Stress Disorder, run by Douglas Mental Health University Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Impact of Events Scale-Revised (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03151681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2022.