Neuroimaging the Impact of Treatment on Neural Substrates of Trust in Post-Traumatic Stress Disorder (PTSD)

• ClinicalTrials.gov Identifier: NCT01244477
• Recruitment Status: Completed
• First Posted: November 19, 2010
• Results First Posted: December 2, 2014
• Last Update Posted: June 27, 2019
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

Traumatic experiences can have a profound negative effect on the lives and well-being of both the people who experience them and their loved ones. For those who experience post-traumatic stress disorder (PTSD), their interpersonal difficulties and social support further impact the success of treatment such that interpersonal difficulties are associated with mistrust and predict poor treatment outcome. In this proposal, the investigators use functional neuroimaging to understand the neurobiology of trust and mistrust in people with PTSD and to learn more about how successful treatment can improve trust and social functioning.

Condition or disease	Intervention/treatment	Phase
Stress Disorders, Post Traumatic; Trust	Behavioral: Group CPT-C	Not Applicable

Detailed Description:

Substantial recent data highlight the role of social functioning as a primary moderator of therapeutic response in individuals with post-traumatic stress disorder (PTSD) such that interpersonal difficulties and mistrust significantly and negatively impact treatment efficacy (Forbes et al., 2003; Forbes et al., 2005; Forbes et al., 2008). In addition, ample evidence suggests that psychotherapy improves the social and interpersonal lives of psychotherapy clients through improving clients' abilities to regulate their emotions and reduce social isolation (Yalom & Leszcz, 2005; Foy et al., 2000). While considerable research has been dedicated to exploring the neurobiology of emotional dysregulation associated with PTSD (Rauch, Shin, & Phelps, 2006; Etkin & Wager, 2007), and increasing data suggest that diverse psychotherapies affect neural functioning (Beauregard 2007), very little is understood about the neurobehavioral pathology underlying the debilitating interpersonal difficulties in PTSD, or the neurobiological mechanisms accompanying the improvements in social functioning that occur with efficacious therapy.

Thus, the broad goals of this project are two-fold. First, the investigators seek to examine the neural substrates associated with interpersonal dysfunction in PTSD using a social exchange game previously developed to assess interpersonal trust and cooperation in healthy (King-Casas et al., 2005) and psychiatric groups (Chiu et al., 2008; King-Casas et al., 2008). Second, the investigators seek to examine changes in neurobehavioral substrates of social functioning following treatment for Veterans with PTSD. Specifically, the investigators propose to use functional magnetic resonance imaging (fMRI) and behavior within a well-characterized Trust Game to examine the neural substrates associated with interpersonal trust and cooperation in Veterans with PTSD prior to and following empirically supported psychotherapy cognitive processing therapy (CPT) for PTSD.

Thus, the broad goals of this project are two-fold. First, the investigators seek to examine the neural substrates associated with interpersonal dysfunction in PTSD using a social exchange game previously developed to assess interpersonal trust and cooperation in healthy (King-Casas et al., 2005) and psychiatric groups (Chiu et al., 2008; King-Casas et al., 2008). Second, the investigators seek to examine changes in neurobehavioral substrates of social functioning following treatment for veterans with PTSD. Specifically, the investigators propose to use functional magnetic resonance imaging (fMRI) and behavior within a well-characterized Trust Game to examine the neural substrates associated with interpersonal trust and cooperation in veterans with PTSD prior to and following empirically supported psychotherapy cognitive processing therapy (CPT) for PTSD.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Neuroimaging the Impact of Treatment on Neural Substrates of Trust in PTSD
• Actual Study Start Date: May 16, 2011
• Actual Primary Completion Date: May 31, 2013
• Actual Study Completion Date: June 30, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: CPT-C; Participants in group CPT-C	Behavioral: Group CPT-C; Participants will be randomly assigned to participate in CPT-C or a 12 week waitlist control group. Waitlist control subjects will participate in CPT-C after the 12 weeks.
No Intervention: Treatment-as-Usual; Participants randomly assigned to the Waitlist Control Group (who will participate in CPT-C after 12 weeks).

Outcome Measures

Primary Outcome Measures :

1. Continuous Whole Brain Imaging With Standard Imaging Parameters for Each Functional Magnetic Resonance Imaging (fMRI) Scan [ Time Frame: Pre & post a 12 week treatment group ]
2. The Clinician Administered PTSD Scale (CAPS) [ Time Frame: Pre & post a 12 week treatment group ]
   The CAPS is considered the gold standard measure of PTSD symptoms. CAPS scores are the sum of 17 questions. Each is question is scored from 0 (best possible outcome) to 8 (worst possible outcome). The lowest possible CAPS score is a 0, indicating no PTSD symptoms reported. The highest possible CAPS score is a 136, indicating the most PTSD symptoms reported.

Secondary Outcome Measures :

1. Behavioral Expression of Trust on the Trust Game [ Time Frame: Pre & post a 12 week treatment group ]
   The Investment Ratio (IR) is the amount subjects were willing to invest in a social partner. It is considered a measure of interpersonal trust, and co-operation. It is a ratio ranging from 0 (indicating no willingness to trust a social partner) to 1.0 (willing to totally trust a social partner). It consists of the percentage of total points the subject was willing to invest in a social partner divided by the total points they received for all ten rounds of the trust game. Higher ratio's indicate more trust.
2. PTSD Checklist (PCL) [ Time Frame: Administered each week at weekly group sessions or pre-post treatment as usual ]
   An instrument measuring a participants self-reported level of PTSD symptoms. PCL scores are the sum of 17 questions. Each is question is scored from 1 (best possible outcome) to 5 (worst possible outcome). The lowest possible PCL score is a 17, indicating no troublesome PTSD symptoms reported. The highest possible PCL score is a 85, indicating the worst degree of PTSD symptoms reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meet criteria for PTSD on the Clinician Administered PTSD Scale (CAPS)
• Priority will be given to Veterans aged 18-50 who have had an onset of symptoms in the past 10 years and are Veterans of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF)
• Have been referred for placement in CPT treatment by a clinician in the Trauma Recovery Program at the Michael E DeBakey VA Medical Center (MEDVAMC) or an eligible Veteran who contacts study staff.
• Are able to see the computer display clearly with or without magnetic Resonance imaging (MRI)-compatible corrective lenses
• Are free from current non-psychiatric medical problems impacting cognitive functioning.
• Are cleared to participate by a treating MEDVAMC clinician
• Are able to participate in functional MRI (fMRI)

Exclusion Criteria:

• Meet Diagnostic and Statistical Manual-IV (DSM-IV)criteria for drug or alcohol abuse in the past 30 days

• History of moderate to severe traumatic brain injury based on any of the following:

  • (i) Glasgow Coma Score < 13
  • (ii)alteration of consciousness > 24 hours; loss of consciousness,30 minutes

• Presence of contraindications to MRI, including but not limited to:

  • claustrophobia
  • pacemaker
  • metal in eyes
  • other implants

• Current neurological or general medical conditions known to impact cognitive and/or emotional functioning, including but limited to:

  • epilepsy
  • Parkinson's disease
  • Huntington's disease
  • Alzheimer's disease
  • stroke
  • chemotherapy for cancer
• Acute psychological instability as assessed by a Michael E DeBakey VA Medical Center (MEDVAMC) clinician or study staff

• Concurrent diagnosis of:

  • schizophrenia
  • schizoaffective disorder
  • delusional disorder
  • organic psychosis
  • and subjects taking antipsychotic medication

Contacts and Locations

Locations

United States, Texas

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States, 77030

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Wright Williams, PhD; Michael E. DeBakey VA Medical Center, Houston, TX

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01244477
• Other Study ID Numbers: B7760-P
• First Posted: November 19, 2010
• Results First Posted: December 2, 2014
• Last Update Posted: June 27, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:

Stress Disorders, Post Traumatic; Trust; functional Magnetic Resonance Imaging (fMRI)

Additional relevant MeSH terms:

Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders