Propranolol Reactivation Mismatch (PRM) Treatment for PTSD

Phase 4

• Conditions: Stress Disorders, Post-Traumatic
• Interventions: Drug: Reactivation Mismatch

• Registration Number: NCT03652922
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The aim of the proposed work is to gather pilot data from an attempt to enhance the ability of propranolol reactivation (PR) to improve PTSD symptoms by incorporating into the design a mismatch (PRM) between what is expected and what occurs while a subject reads a narrative of the traumatic event that caused their PTSD under the influence of the ß-adrenergic blocking drug propranolol. It is hypothesized that a series of PRM treatments will produce superior symptomatic decreases compared to what the investigators have found in prior, published studies using PR without mismatch.

Under certain circumstances, retrieval (reactivation) of a traumatic memory returns it to a deconsolidated state from which it must be reconsolidated if it is to persist. Concomitant administration of the ß-adrenergic blocker weakens a deconsolidated traumatic memory and reduces PTSD symptoms, presumably through blockade of reconsolidation. It has recently been discovered that in order for deconsolidation to occur, there must be a mismatch between what is expected and what actually occurs. Altering the context in which a traumatic memory is retrieved putatively represents a deconsolidation-promoting mismatch. Experimentally increasing mismatch by manipulating context may make propranolol more effective in the treatment of PTSD.

The design is a single-blind, placebo-controlled, randomized PRM clinical trial by Partners researchers in 11 convenience pilot subjects between ages 18 and 65 with active PTSD, using a 10:1 propranolol:placebo randomization schedule. This two-month study will have the following components: Pre-treatment psychometric evaluation; Treatment consisting of six weekly PRM sessions with propranolol, or placebo; Post-treatment psychometric evaluation; Six-month follow-up psychometric evaluation. The Clinician-Administered PTSD Scale (CAPS) and PTSD Checklist (PCL) will be administered at pre- and post-treatment and at follow-up. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) will also be administered at the pre-treatment evaluation. The PCL will also be administered prior to each weekly treatment session.

Pilot data analysis will consist of calculation of percent improvements and effect sizes in CAPS-5 and PCL-5 scores; observational comparisons with results obtained without mismatch in prior published studies; informal statistical comparisons via t-tests; and calculation of effect sizes for power analysis for a subsequent definitive study, if indicated.

Detailed Description

Not available

Study Timeline

• Status Verified: 2018-08
• Study First Submitted: 2018-08-22
• Study First Submitted QC: 2018-08-28
• Last Update Submitted: 2018-08-28
• Study First Posted: 2018-08-29
• Last Update Posted: 2018-08-29
• Study Start: 2018-09
• Primary Completion: 2019-11
• Study Completion: 2019-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Propranolol	Reactivation Mismatch	-
Placebo	Reactivation Mismatch	-

Primary Outcome Measures

Name	Time	Method
PTSD Checklist for DSM-5 (PCL-5) Change Score	Change from Baseline at Week 0 to Post-Treatment at Week 7	The PCL-5 is a published, validated, 20-item questionnaire, corresponding to the DSM-5 symptom criteria for PTSD. The self-report rating scale is 0-4 for each symptom. Possible scores range from 0 to 80.