NCT03652922

Propranolol Reactivation Mismatch (PRM) Treatment for PTSD

Propranolol Reactivation Mismatch (PRM) Treatment for PTSD: A Pilot Study

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 11 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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.

Conditions

• Stress Disorders, Post-Traumatic

Interventions

Type	Name	Description
DRUG	Reactivation Mismatch	Ninety minutes prior to each of six weekly traumatic memory reactivation sessions, the subject will be given 0.67 mg/kg of short-acting propranolol (or placebo), rounded up to the nearest 10 mg (minimum 40 mg) and 1 mg/kg of oral long-acting propranolol or placebo (minimum 60 mg). rounded so as to achieve a dose of 60, 80, 120, or 160 mg. The subject will then read a narrative of their personal traumatic event aloud. During each weekly reading, a simple, different "mismatch" condition will be created by having the subject do such things as whisper the narrative, skip over every word that contains the letter "e," pronounce the narrative in a different accent, or alter the tense and/or person of the narrative.

Timeline

• Start date: 2018-09-01
• Primary completion: 2019-11-01
• Completion: 2019-11-01
• First posted: 2018-08-29
• Last updated: 2018-08-29

Regulatory

• FDA-regulated drug study