Recruiting

Propranolol vs. Standard

Sponsor:

Massachusetts General Hospital

Code:

NCT05853627

Conditions

Stress Disorders, Post-Traumatic

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Memory reactivation procedures

Propranolol

Study Details

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

Study ID

NCT05853627

Start date

Jun 15, 2023

Status verified date

May, 2026

Completion date

Jul 1, 2026

Anticipated

Primary completion date

Jul 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Initial participants will be males or females 18-65 years old who have experienced a traumatic event that meets the DSM-5 PTSD A criterion, and whose PCL-5 score is >33 (to maximize the likelihood that they will meet our psychophysiological inclusion criterion). In order to be randomized, participants must further meet this psychophysiological inclusion criterion during baseline script-driven imagery testing Although we do not require a diagnosis of PTSD, because we have set a minimum psychophysiological inclusion criterion and a valid Criterion A traumatic event, our sample will include a substantial number, likely a majority, of PTSD participants.

Exclusion Criteria:

1. 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.
2. Medical condition that contraindicates PPNL, e.g., congestive heart failure, heart block, insulin- requiring diabetes, chronic bronchitis, emphysema, or asthma. Asthma attacks will only be exclusionary if they: a) occurred within the past ten years, b) occurred at any time in life if induced by a β-blocker, or c) are currently being treated
3. Previous adverse reaction to, or non-compliance with, a β-blocker
4. 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)
5. Presence of drugs of abuse, including opiates, marijuana, cocaine, amphetamines, or alcohol at the initial assessment
6. Pregnancy or breast feeding. Women of childbearing potential will have a pregnancy test at the initial assessment
7. Presence of a contraindicating psychiatric condition, e.g., psychotic, bipolar, melancholic, or active substance use disorder; or suicidality (see below)
8. 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
9. 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
10. Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation
11. Participant candidate does not understand English. This exclusion criterion is necessary because the procedures require a nuanced dialogue with English-speaking investigators.

Study Design

Enrollment

80 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Mismatch reactivation condition

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.

active comparator: Standard reactivation condition

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.

Interventions

Memory reactivation procedures

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.

Propranolol

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

Primary outcome measure

  • Composite score of psychophysiological reactivity (comprising heart rate, skin conductance, and electromyography of the left corrugator muscle) using the Biopac system. [ Time Frame: Baseline (week 0) ]
  • Composite score of psychophysiological reactivity (comprising heart rate, skin conductance, and electromyography of the left corrugator muscle) using the Biopac system. [ Time Frame: 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. [ Time Frame: Follow up (week 11) ]

Central Contacts and Locations

Central contacts

Locations

Massachusetts General Hospital Home Base Program

Recruiting

Charlestown, Massachusetts, United States, 02129

Contacts

More Information

Sponsor

Massachusetts General Hospital

Last update posted

May 6, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-05-06.