RECRUITING

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

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2023-06-15
Study Completion:2025-06-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05853627

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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.
  1. 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. 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. 3. Previous adverse reaction to, or non-compliance with, a β-blocker
  4. 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. 5. Presence of drugs of abuse, including opiates, marijuana, cocaine, amphetamines, or alcohol at the initial assessment
  6. 6. Pregnancy or breast feeding. Women of childbearing potential will have a pregnancy test at the initial assessment
  7. 7. Presence of a contraindicating psychiatric condition, e.g., psychotic, bipolar, melancholic, or active substance use disorder; or suicidality (see below)
  8. 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. 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. 10. Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation
  11. 11. Participant candidate does not understand English. This exclusion criterion is necessary because the procedures require a nuanced dialogue with English-speaking investigators.

Contacts and Locations

Study Contact

James Cappellucci
CONTACT
857.282.1724
jcappellucci@partners.org

Study Locations (Sites)

Massachusetts General Hospital Home Base Program
Charlestown, Massachusetts, 02129
United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-15
Study Completion Date2025-06-01

Study Record Updates

Study Start Date2023-06-15
Study Completion Date2025-06-01

Terms related to this study

Additional Relevant MeSH Terms

  • Stress Disorders, Post-Traumatic