Mismatch vs. Standard Intervention During Memory Reconsolidation Blockade With Propranolol: Effect on Psychophysiological Reactivity During Traumatic Imagery

NCT05853627 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 1R21MH131987-01A1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed R21 project will attempt to further develop a novel intervention for posttraumatic stress symptoms inspired by the science of memory reconsolidation. Work in normal humans has shown that when a stable, consolidated memory is reactivated (i.e., retrieved) under appropriate conditions, it reverts to an unstable state, a process referred to herein as deconsolidation. In such a state, the memory is susceptible to the action of various "amnestic" agents that may inhibit its reconsolidation, thereby weakening it. The β-adrenergic blocker propranolol (PPNL) possesses such amnestic properties. More recent research has found that in order to initiate deconsolidation, there must be a prediction error, or mismatch, between what is expected and what occurs when the memory is reactivated. Prior placebo-controlled, randomized clinical trials (PBO-RCT) from our laboratory have found that when propranolol is administered concomitant with the reactivation of a psychologically traumatic memory, the memory is weakened, as revealed by subsequent lower physiological (heart rate, skin conductance, facial electromyogram) responding during script-driven mental imagery. Clinical applicability was evaluated in a PBO-RCT, in which PTSD participants receiving propranolol underwent six weekly sessions of 10-20 min of "standard" (STD) traumatic memory reactivation stimulated by reading a narrative. At post-treatment, these participants showed a greater reduction of PTSD symptoms compared to participants who had taken PBO. The goal of the proposed study is to test whether intentionally incorporating innovative mismatch (MM) into traumatic memory reactivation can improve upon physiological responding during script-driven mental imagery. Participants will be randomized to one of 2 treatment arms: STD/PPNL and MM/PPNL. A baseline assessment will measure psychophysiological responsivity to script-driven mental imagery (target measure). PPNL will be administered 90-min prior to each of six weekly 10-20 min. traumatic memory reactivation sessions. In the MM condition, a different, unexpected mismatch (e.g., singing the narrative) will be incorporated into the reactivation. In the STD condition, the participant will read the narrative the same way each time. The focus of the R21 proposal will be to assess whether the MM/PPNL group shows lower subsequent physiological responses than the STD/PPNL group

Conditions

Stress Disorders, Post-Traumatic

Outcome Measures

Primary Outcomes (3)

• Composite score of psychophysiological reactivity (comprising heart rate, skin conductance, and electromyography of the left corrugator muscle) using the Biopac system.

  psychophysiological responding during script-driven traumatic imagery compared to no imagery.

  Baseline (week 0)

• Composite score of psychophysiological reactivity (comprising heart rate, skin conductance, and electromyography of the left corrugator muscle) using the Biopac system.

  psychophysiological responding during script-driven traumatic imagery compared to no imagery.

  Post-treatment (week 7)

• Composite score of psychophysiological reactivity (comprising heart rate, skin conductance, and electromyography of the left corrugator muscle) using the Biopac system.

  psychophysiological responding during script-driven traumatic imagery compared to no imagery.

  Follow up (week 11)

Study Arms (2)

Mismatch reactivation condition

EXPERIMENTAL

The participant will recite their trauma narrative to the psychologist for 10-20 minutes. However, during each recitation, a "mismatch" condition, different for each session, will be added to the reactivation procedure by having the participant do the following (in order of sessions.

Behavioral: Memory reactivation procedures; Drug: Propranolol

Standard reactivation condition

ACTIVE COMPARATOR

The intervention will be the same for each of the six intervention sessions. The participant will recite to the psychologist the narrative they previously composed for 10-20 min. The psychologist will congratulate the participant for having succeeded in this task and advise them they are finished for the day.

Behavioral: Memory reactivation procedures; Drug: Propranolol

Interventions

Memory reactivation procedures BEHAVIORAL

In the Mismatch condition, a different, unexpected mismatch will be incorporated into the reactivation. In the Standard condition, the participant will read the narrative the same way each time.

Mismatch reactivation condition; Standard reactivation condition

Propranolol DRUG

Propranolol will be administered 60-min prior to each of six weekly 10-20 min. traumatic memory reactivation sessions.

Mismatch reactivation condition; Standard reactivation condition

Eligibility Criteria

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

You may not qualify if:

• Basal sitting or standing systolic blood pressure \<90/60 mm Hg or basal HR \<50 BPM. Those participant-candidates excluded for this reason with such readings will be counseled and referred for further clinical consultation if symptomatic or if they wish to be referred even if asymptomatic.
• Previous adverse reaction to, or non-compliance with, a β-blocker
• Current use of medication that may involve potentially dangerous or confounding interactions with PPNL, including anti- hypertensives, antiarrhythmics, and benzodiazepines. (Possible inhibition of CYP2D6 isoenzyme-dependent reactions will not be of concern in this study, because PPNL will only be administered once a week)
• Presence of drugs of abuse, including opiates, marijuana, cocaine, amphetamines, or alcohol at the initial assessment
• Pregnancy or breast feeding. Women of childbearing potential will have a pregnancy test at the initial assessment
• Presence of a contraindicating psychiatric condition, e.g., psychotic, bipolar, melancholic, or active substance use disorder; or suicidality (see below)
• Initiation of, or change in, psychotropic medication within the previous two months. For participants receiving stable doses of pharmacotherapy, they and their clinicians-prescribers will be asked not to alter the regimen during the proposed two-month study period (excluding the one-month follow-up) except in clinically urgent circumstances. If this becomes necessary, a decision will be made on a case-by-case basis about retaining the participant or terminating participation
• Current participation in any psychotherapy other than supportive. Participants will be asked not to initiate new psychotherapy during the proposed two-month study period (excluding the one-month follow-up) except in clinically urgent circumstances. If this becomes necessary, a decision will be made on a case-by-case basis about retaining the participant or terminating participation
• Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital Home Base Program

Charlestown, Massachusetts, 02129, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

James Cappellucci

CONTACT

857.282.1724; jcappellucci@partners.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomly assigned to the STD vs. MM condition. The psychophysiology assessor, who will perform the data analysis, will be blind to Condition.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Director of Research, The Home Base Program

Model Details: The efficacy of the MM intervention will be contrasted with a standard (STD) reactivation condition that does not include an intentional MM component. We will randomize ndividuals who have experienced a traumatic event and meet our entry criteria (please see research strategy) to one of the two treatment arms: STD/PPNL and MM/PPNL. Participants' psychophysiological (heart rate, skin conductance, corrugator electromyogram (EMG)) responses during script driven imagery of their traumatic event will constitute the R21 target.

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 11, 2023
• Study Start: June 15, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)