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Brain Imaging of Psychotherapy for Posttraumatic Stress Disorder (PTSD)

Primary Purpose

Posttraumatic Stress Disorder (PTSD)

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Prolonged exposure
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Posttraumatic Stress Disorder (PTSD) focused on measuring Posttraumatic Stress Disorder (PTSD), Psychotherapy, non-medication treatment, Prolonged Exposure, Transcranial Magnetic Stimulation (TMS), Anxiety Disorders, emotion, emotion regulation, functional MRI, Affective Symptoms

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. age between 18 and 60 years;
  2. fMRI scanning eligibility, including no evidence of any form of metal embedded in the body (e.g., metal wires, nuts, bolts, screws, plates, sutures), as these produce artifacts when brain imaging;
  3. not currently involved in an exposure-based psychotherapy, in order to be able to measure and interpret the effects of PE on PTSD;
  4. must comprehend English well and show non-impaired intellectual abilities to ensure adequate comprehension of the fMRI task instructions and PE treatment;
  5. no history of neurological or cardiovascular disorders, brain surgery, electroconvulsive or radiation treatment, brain hemorrhage or tumor, stroke, seizures or epilepsy, diabetes, hypo- or hyperthyroidism, head trauma with loss of consciousness greater than thirty minutes;
  6. no regular use of benzodiazepine, opiate, thyroid, anticonvulsant or antipsychotic medications. Patients on stable doses of antidepressant medications will be allowed. Patients for whom antidepressant dosing is being actively titrated will be required to be on a stable dose for 1 month prior to inclusion in the study.

Exclusion Criteria:

  • Any contraindication to being scanned in the 3T or 1.5T scanners at the Lucas Center or CNI such as having a pacemaker or implanted device that has not been cleared for scanning at the Lucas Center or CNI.
  • Participants will be excluded from the study if there is any lifetime evidence of psychosis, mania, hypomania, or bipolar disorders. Other axis I comorbidities will not be a cause for exclusion.

In addition, subjects will be excluded if they have a significant CNS neurological condition such as stroke, seizure, tumor, hemorrhage, multiple sclerosis, etc.

Patients who have current substance dependence will be excluded from the study. A recent diagnosis of substance abuse is allowable, however, as long as subjects have been abstinent for greater than three months.

  • Subjects will be excluded if they are currently in an exposure-based psychotherapy for PTSD.

Sites / Locations

  • VA Palo Alto Healthcare System
  • Stanford University, Department of Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Immediate Prolonged Exposure Treatment

Wait list, immediately followed by Prolonged Exposure

Arm Description

Intake procedures include clinician-administered diagnostic battery, cognitive testing, self-report measures of symptoms, and functional imaging scan. Participants in this arm will complete a concurrent TMS/fMRI scan before beginning Prolonged Exposure (PE). PE will be delivered in 9-12 90-minute sessions. Therapy will be delivered by PhD-level therapists at Stanford and Palo Alto VA.

Intake procedures include clinician-administered diagnostic battery, cognitive testing, self-report measures of symptoms, and functional imaging scan. NOTE: Participants in this arm receive treatment following a waitlist period of 12 weeks. After waitlist, will have a TMS/fMRI scan and then immediately begin Prolonged Exposure treatment. See above for description of Prolonged Exposure.

Outcomes

Primary Outcome Measures

Clinician Administered PTSD scale (CAPS)
The CAPS is a 30-item structured interview that corresponds to the DSM-IV criteria for PTSD. In addition to assessing the 17 PTSD symptoms, questions target the impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and frequency and intensity of five associated symptoms (guilt over acts, survivor guilt, gaps in awareness, depersonalization, and derealization). For each item, standardized questions and probes are provided.

Secondary Outcome Measures

Mood and Anxiety Symptom Questionnaire (MASQ)
Treatment success based on Improvement on subscales of the MASQ, including decreased anxious arousal and decreased anhedonic depression, from pre- to post-treatment assessment
fMRI-assessed resting connectivity
From pre- to post-treatment, improve will be based on enhanced functional connectivity
Implicit emotion regulation
Implicit emotion regulation assessed through emotion conflict task performed during functional imaging. Performance based on reaction time and recruitment of emotion regulation regions during the task.

Full Information

First Posted
December 14, 2011
Last Updated
January 19, 2017
Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH), VA Office of Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT01507948
Brief Title
Brain Imaging of Psychotherapy for Posttraumatic Stress Disorder (PTSD)
Official Title
The Neurobiology of Psychotherapy: Emotional Reactivity and Regulation in PTSD
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH), VA Office of Research and Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators are seeking people who have been exposed to a traumatic event in the past and have symptoms of posttraumatic stress disorder (PTSD) currently. A person with PTSD may feel significant distress when reminded of a traumatic event or feel depressed, anxious or jumpy. As a part of this study, participants will receive brain MRIs and office assessments before and after psychotherapy. The investigators provide the gold-standard psychotherapy for PTSD, "Prolonged Exposure", free of charge; additionally participants are compensated for their time during assessment procedures. This study is exploring the brain circuitry involved in improvement in response to psychotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Posttraumatic Stress Disorder (PTSD)
Keywords
Posttraumatic Stress Disorder (PTSD), Psychotherapy, non-medication treatment, Prolonged Exposure, Transcranial Magnetic Stimulation (TMS), Anxiety Disorders, emotion, emotion regulation, functional MRI, Affective Symptoms

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Immediate Prolonged Exposure Treatment
Arm Type
Experimental
Arm Description
Intake procedures include clinician-administered diagnostic battery, cognitive testing, self-report measures of symptoms, and functional imaging scan. Participants in this arm will complete a concurrent TMS/fMRI scan before beginning Prolonged Exposure (PE). PE will be delivered in 9-12 90-minute sessions. Therapy will be delivered by PhD-level therapists at Stanford and Palo Alto VA.
Arm Title
Wait list, immediately followed by Prolonged Exposure
Arm Type
No Intervention
Arm Description
Intake procedures include clinician-administered diagnostic battery, cognitive testing, self-report measures of symptoms, and functional imaging scan. NOTE: Participants in this arm receive treatment following a waitlist period of 12 weeks. After waitlist, will have a TMS/fMRI scan and then immediately begin Prolonged Exposure treatment. See above for description of Prolonged Exposure.
Intervention Type
Behavioral
Intervention Name(s)
Prolonged exposure
Intervention Description
PE will be delivered in 9-12 90-minute sessions. Therapy will be delivered by PhD-level therapists at Stanford and Palo Alto VA. PE consists of four components: psychoeducation about PTSD symptoms and the behavioral or cognitive factors maintaining it, a brief breathing retraining that can be used as a stress management tool, prolonged imaginal exposure to the trauma memory both within-session and repeated as homework, and prolonged in vivo exposure to avoided scenarios in patients' day-to-day lives.
Primary Outcome Measure Information:
Title
Clinician Administered PTSD scale (CAPS)
Description
The CAPS is a 30-item structured interview that corresponds to the DSM-IV criteria for PTSD. In addition to assessing the 17 PTSD symptoms, questions target the impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and frequency and intensity of five associated symptoms (guilt over acts, survivor guilt, gaps in awareness, depersonalization, and derealization). For each item, standardized questions and probes are provided.
Time Frame
Before and after Prolonged Exposure Treatment, which is expected to take approximately six weeks.
Secondary Outcome Measure Information:
Title
Mood and Anxiety Symptom Questionnaire (MASQ)
Description
Treatment success based on Improvement on subscales of the MASQ, including decreased anxious arousal and decreased anhedonic depression, from pre- to post-treatment assessment
Time Frame
Before and after Prolonged Exposure Treatment, which is expected to take approximately six weeks.
Title
fMRI-assessed resting connectivity
Description
From pre- to post-treatment, improve will be based on enhanced functional connectivity
Time Frame
Before and after Prolonged Exposure Treatment, which is expected to take approximately six weeks.
Title
Implicit emotion regulation
Description
Implicit emotion regulation assessed through emotion conflict task performed during functional imaging. Performance based on reaction time and recruitment of emotion regulation regions during the task.
Time Frame
Assessed 4 times: Before beginning Prolonged Exposure, after the third week of therapy, after the last therapy session (on average 6 weeks after beginning therapy), and 1 month after the end of therapy.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: age between 18 and 60 years; fMRI scanning eligibility, including no evidence of any form of metal embedded in the body (e.g., metal wires, nuts, bolts, screws, plates, sutures), as these produce artifacts when brain imaging; not currently involved in an exposure-based psychotherapy, in order to be able to measure and interpret the effects of PE on PTSD; must comprehend English well and show non-impaired intellectual abilities to ensure adequate comprehension of the fMRI task instructions and PE treatment; no history of neurological or cardiovascular disorders, brain surgery, electroconvulsive or radiation treatment, brain hemorrhage or tumor, stroke, seizures or epilepsy, diabetes, hypo- or hyperthyroidism, head trauma with loss of consciousness greater than thirty minutes; no regular use of benzodiazepine, opiate, thyroid, anticonvulsant or antipsychotic medications. Patients on stable doses of antidepressant medications will be allowed. Patients for whom antidepressant dosing is being actively titrated will be required to be on a stable dose for 1 month prior to inclusion in the study. Exclusion Criteria: Any contraindication to being scanned in the 3T or 1.5T scanners at the Lucas Center or CNI such as having a pacemaker or implanted device that has not been cleared for scanning at the Lucas Center or CNI. Participants will be excluded from the study if there is any lifetime evidence of psychosis, mania, hypomania, or bipolar disorders. Other axis I comorbidities will not be a cause for exclusion. In addition, subjects will be excluded if they have a significant CNS neurological condition such as stroke, seizure, tumor, hemorrhage, multiple sclerosis, etc. Patients who have current substance dependence will be excluded from the study. A recent diagnosis of substance abuse is allowable, however, as long as subjects have been abstinent for greater than three months. Subjects will be excluded if they are currently in an exposure-based psychotherapy for PTSD.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Etkin, M.D., Ph.D.
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Madeleine S Goodkind, Ph.D.
Organizational Affiliation
Stanford University
Official's Role
Study Director
Facility Information:
Facility Name
VA Palo Alto Healthcare System
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Stanford University, Department of Psychiatry
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28715908
Citation
Fonzo GA, Goodkind MS, Oathes DJ, Zaiko YV, Harvey M, Peng KK, Weiss ME, Thompson AL, Zack SE, Lindley SE, Arnow BA, Jo B, Gross JJ, Rothbaum BO, Etkin A. PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation. Am J Psychiatry. 2017 Dec 1;174(12):1163-1174. doi: 10.1176/appi.ajp.2017.16091072. Epub 2017 Jul 18.
Results Reference
derived
PubMed Identifier
28715907
Citation
Fonzo GA, Goodkind MS, Oathes DJ, Zaiko YV, Harvey M, Peng KK, Weiss ME, Thompson AL, Zack SE, Mills-Finnerty CE, Rosenberg BM, Edelstein R, Wright RN, Kole CA, Lindley SE, Arnow BA, Jo B, Gross JJ, Rothbaum BO, Etkin A. Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD. Am J Psychiatry. 2017 Dec 1;174(12):1175-1184. doi: 10.1176/appi.ajp.2017.16091073. Epub 2017 Jul 18.
Results Reference
derived

Learn more about this trial

Brain Imaging of Psychotherapy for Posttraumatic Stress Disorder (PTSD)

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