Ignite Creation Date:
2024-05-06 @ 6:59 PM
Last Modification Date:
2024-10-26 @ 2:58 PM
Study NCT ID:
NCT05853627
Status:
RECRUITING
Last Update Posted:
2024-04-11
First Post:
2023-04-20
Brief Title:
Mismatch vs Standard Intervention During Memory Reconsolidation Blockade With Propranolol Effect on Psychophysiological Reactivity During Traumatic Imagery
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
Mismatch vs Standard Intervention During Memory Reconsolidation Blockade With Propranolol Effect on Psychophysiological Reactivity During Traumatic Imagery
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 ie 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 STDPPNL and MMPPNL 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 eg 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 MMPPNL group shows lower subsequent physiological responses than the STDPPNL group
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 STDPPNL and MMPPNL 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 eg 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 MMPPNL group shows lower subsequent physiological responses than the STDPPNL group
Detailed Description:
The proposed project under the R21 Basic Experimental Studies Involving Humans BESH mechanism aims to test whether adding mismatch MM to traumatic memory reactivation under the influence of the beta-noradrenergic blocker propranolol PPNL compared to no mismatch reactivation further reduces physiological reactivity during script driven imagery of the traumatic event We propose that the mechanism for the propranolol MM treatment is a deconsolidation of the traumatic memory instigated by MM followed by b blockade of the reconsolidation of the memory by the amnestic agent PPNL 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 individuals who have experienced a traumatic event and meet our entry criteria please see research strategy to one of the two treatment arms STDPPNL and MMPPNL Participants psychophysiological heart rate skin conductance corrugator electromyogram EMG responses during script driven imagery of their traumatic event will constitute the R21 target
On the initial assessment day participant candidates will be screened for eligibility based upon the inclusionexclusion criteria After the candidate provides written informed consent a doctoral-level clinician will administer the psychometric instruments Participant candidates will complete a narrative describing the traumatic event that caused PTSD
Based on the narrative the psychologist will then prepare a 100-word script portraying the most salient aspect hot spot of the narrative which will be recorded for audio playback in the psychophysiology laboratory Participants not physiologically reactive to the traumatic script will be excluded If all of the foregoing is completed successfully participants will be randomized to one of the two arms above
The participant will return to the clinic one week later for the first of six weekly intervention sessions Ninety min prior to its commencement the participant will ingest the study medication The participant will then recite the narrative aloud for 10-20 min In the STD condition the participant will recite the narrative in an expected manner ie in the same way during each session In the MM condition the participant will recite the narrative in an unexpected manner different for each weekly session Examples of unexpected conditions will include such things as reciting their narrative while skipping over each word that contains the letter e and reciting the narrative in a make-believe accent A week following the final intervention session the participant will return for the post-treatment psychophysiological testing These will be repeated at the one-month follow-up session
The data will be analyzed by hierarchical linear modeling and regression techniques The projected sample sizes will provide adequate power to test the proposed studys hypotheses see Design and Power Analysis section
On the initial assessment day participant candidates will be screened for eligibility based upon the inclusionexclusion criteria After the candidate provides written informed consent a doctoral-level clinician will administer the psychometric instruments Participant candidates will complete a narrative describing the traumatic event that caused PTSD
Based on the narrative the psychologist will then prepare a 100-word script portraying the most salient aspect hot spot of the narrative which will be recorded for audio playback in the psychophysiology laboratory Participants not physiologically reactive to the traumatic script will be excluded If all of the foregoing is completed successfully participants will be randomized to one of the two arms above
The participant will return to the clinic one week later for the first of six weekly intervention sessions Ninety min prior to its commencement the participant will ingest the study medication The participant will then recite the narrative aloud for 10-20 min In the STD condition the participant will recite the narrative in an expected manner ie in the same way during each session In the MM condition the participant will recite the narrative in an unexpected manner different for each weekly session Examples of unexpected conditions will include such things as reciting their narrative while skipping over each word that contains the letter e and reciting the narrative in a make-believe accent A week following the final intervention session the participant will return for the post-treatment psychophysiological testing These will be repeated at the one-month follow-up session
The data will be analyzed by hierarchical linear modeling and regression techniques The projected sample sizes will provide adequate power to test the proposed studys hypotheses see Design and Power Analysis section
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None