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Propranolol Reactivation Mismatch (PRM) Treatment for PTSD

Primary Purpose

Stress Disorders, Post-Traumatic

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Reactivation Mismatch
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stress Disorders, Post-Traumatic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria

• Convenience sample of pilot subjects between ages 18 and 65 with active PTSD

Exclusion Criteria

  • Age <18 or >65;
  • Basal systolic blood pressure <100 mm Hg or heart rate <55 beats per minute;
  • Medical condition that contraindicates the administration of propranolol, e.g., history of congestive heart failure, heart block, insulin-requiring diabetes, chronic bronchitis, emphysema, or asthma. With regard to asthma, because many persons who say they have had an asthma attack, especially as a child, may only have had hay fever, another allergy, or another non-asthmatic episode, a blanket exclusion criterion may be overly restrictive. Therefore, 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, regardless of the date of last occurrence;
  • Previous adverse reaction to, or non-compliance with, a β-blocker
  • Current use of medication that may involve potentially dangerous interactions with propranolol, including, other β-adrenergic blockers, antiarrhythmics, calcium channel blockers and benzodiazepines. Subjects taking an α-1-adrenergic antagonist (e.g., prazosin) or an α -1-adrenergic agonist (e.g., clonidine) will be asked to refrain from taking this medication on the day of a study medication visit. Note: Possible inhibition of CYP2D6 isoenzyme-dependent reactions will not be of concern in this study, because propranolol will only be administered once a week for six weeks;
  • Presence of drugs of abuse, including opiates, marijuana, cocaine, or amphetamines, as determined by saliva or urine testing;
  • Pregnancy or breast feeding. Women of childbearing age will have a pregnancy test prior to being administered study medication at study week 0, and again at study week 7, following study medication discontinuation;
  • Current PTSD from a traumatic event other than the event being treated, or another contraindicating psychiatric condition, e.g., current psychotic, bipolar, melancholic, or active substance dependence or abuse disorder;
  • Initiation of, or change in, psychotropic medication within the previous two months. For subjects receiving stable doses of pharmacotherapy, they and their providers will be asked not to change the regimen during the proposed two-month study (excluding the 6-month follow-up) except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the subject or terminating participation
  • Current participation in any psychotherapy (other than supportive). Subjects will be asked not to initiate new psychotherapy during the proposed two-month study (excluding the 6-month follow-up) except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the subject or terminating participation;
  • Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation;
  • Subject candidate does not understand English. This exclusion criterion is necessary because the procedures require a subtle dialogue with solely English-speaking investigators, which translation cannot accomplish. There is a need for rapid communication with English-speaking investigators in case of an adverse drug effect.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Propranolol

    Placebo

    Arm Description

    Outcomes

    Primary Outcome Measures

    PTSD Checklist for DSM-5 (PCL-5) Change Score
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    August 22, 2018
    Last Updated
    August 28, 2018
    Sponsor
    Massachusetts General Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03652922
    Brief Title
    Propranolol Reactivation Mismatch (PRM) Treatment for PTSD
    Official Title
    Propranolol Reactivation Mismatch (PRM) Treatment for PTSD: A Pilot Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Unknown status
    Study Start Date
    September 2018 (Anticipated)
    Primary Completion Date
    November 2019 (Anticipated)
    Study Completion Date
    November 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Massachusetts General Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Stress Disorders, Post-Traumatic

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    11 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Propranolol
    Arm Type
    Experimental
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Reactivation Mismatch
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    PTSD Checklist for DSM-5 (PCL-5) Change Score
    Description
    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.
    Time Frame
    Change from Baseline at Week 0 to Post-Treatment at Week 7

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria • Convenience sample of pilot subjects between ages 18 and 65 with active PTSD Exclusion Criteria Age <18 or >65; Basal systolic blood pressure <100 mm Hg or heart rate <55 beats per minute; Medical condition that contraindicates the administration of propranolol, e.g., history of congestive heart failure, heart block, insulin-requiring diabetes, chronic bronchitis, emphysema, or asthma. With regard to asthma, because many persons who say they have had an asthma attack, especially as a child, may only have had hay fever, another allergy, or another non-asthmatic episode, a blanket exclusion criterion may be overly restrictive. Therefore, 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, regardless of the date of last occurrence; Previous adverse reaction to, or non-compliance with, a β-blocker Current use of medication that may involve potentially dangerous interactions with propranolol, including, other β-adrenergic blockers, antiarrhythmics, calcium channel blockers and benzodiazepines. Subjects taking an α-1-adrenergic antagonist (e.g., prazosin) or an α -1-adrenergic agonist (e.g., clonidine) will be asked to refrain from taking this medication on the day of a study medication visit. Note: Possible inhibition of CYP2D6 isoenzyme-dependent reactions will not be of concern in this study, because propranolol will only be administered once a week for six weeks; Presence of drugs of abuse, including opiates, marijuana, cocaine, or amphetamines, as determined by saliva or urine testing; Pregnancy or breast feeding. Women of childbearing age will have a pregnancy test prior to being administered study medication at study week 0, and again at study week 7, following study medication discontinuation; Current PTSD from a traumatic event other than the event being treated, or another contraindicating psychiatric condition, e.g., current psychotic, bipolar, melancholic, or active substance dependence or abuse disorder; Initiation of, or change in, psychotropic medication within the previous two months. For subjects receiving stable doses of pharmacotherapy, they and their providers will be asked not to change the regimen during the proposed two-month study (excluding the 6-month follow-up) except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the subject or terminating participation Current participation in any psychotherapy (other than supportive). Subjects will be asked not to initiate new psychotherapy during the proposed two-month study (excluding the 6-month follow-up) except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the subject or terminating participation; Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation; Subject candidate does not understand English. This exclusion criterion is necessary because the procedures require a subtle dialogue with solely English-speaking investigators, which translation cannot accomplish. There is a need for rapid communication with English-speaking investigators in case of an adverse drug effect.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Roger K Pitman, MD
    Phone
    617-726-5333
    Email
    roger_pitman@hms.harvard.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kaloyan S Tanev, MD
    Phone
    617-880-9587
    Email
    ktanev@bwh.harvard.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Roger K Pitman, MD
    Organizational Affiliation
    Massachusetts General Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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