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

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01244477
• Collaborator: (none)
• Enrollment: 61
• Location: 1
• Arms: 2
• Actual Duration (Months): 85.5
• Patients Per Site Per Month: 0.7

Study Details

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	N/A

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
• 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: Jun 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 [Pre & post a 12 week treatment group]

2. The Clinician Administered PTSD Scale (CAPS) [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 [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) [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01244477
• Other Study ID Numbers: B7760-P
• First Posted: Nov 19, 2010
• Last Update Posted: Jun 27, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

Participant Flow

Arm/Group Title	CPT-C	Treatment-as-Usual
Arm/Group Description	Group Cognitive Processing Therapy-C (CPT-C): Participants who chose to participate in a 12-week CPT-C treatment group.	Participants who chose to participate in a 12-week treatment as usual group and offered CPT-C group treatment after 12 weeks.
Period Title: Overall Study
STARTED	38	23
COMPLETED	18	20
NOT COMPLETED	20	3

Baseline Characteristics

Arm/Group Title	CPT-C	Treatment-as-Usual	Total
Arm/Group Description	Participants in group CPT-C 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.	Participants randomly assigned to the Waitlist Control Group (who will participate in CPT-C after 12 weeks).	Total of all reporting groups
Overall Participants	38	23	61
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	38 100%	23 100%	61 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 18.4%	4 17.4%	11 18%
Male	31 81.6%	19 82.6%	50 82%
Race/Ethnicity, Customized (participants) [Number]
Black/African American	13 34.2%	5 21.7%	18 29.5%
Hispanic or Latino	6 15.8%	5 21.7%	11 18%
Mixed Race	4 10.5%	1 4.3%	5 8.2%
Caucasian or White	15 39.5%	12 52.2%	27 44.3%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Neural data is not analyzable - scanner technicians changed the parameters of the task fMRI on an unpredictable basis. Project staff and data no longer available.

Arm/Group Title	Arm 1: CPT-C Group	Arm 2: Waitlist Control Group
Arm/Group Description	Participants in group CPT-C 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.	Participants randomly assigned to the Waitlist Control Group (who will participate in CPT-C after 12 weeks).
Measure Participants	0	0

2. Primary Outcome

Title	The Clinician Administered PTSD Scale (CAPS)
Description	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.
Time Frame	Pre & post a 12 week treatment group

Outcome Measure Data

Analysis Population Description

We limited this arm to 18 subjects who completed 9+ out of 12 treatment sessions.

Arm/Group Title	CPT-C	Treatment-as-Usual
Arm/Group Description	Participants in group CPT-C Group CPT-C: Participants who chose to participate in a 12-week CPT-C treatment group.	Participants who chose to participate in a 12-week treatment as usual group and offered CPT-C group treatment after 12 weeks.
Measure Participants	18	20
Pre-Therapy or before 12 weeks	79.3 (18.6)	66.3 (26.2)
Post-Therapy or after 12 weeks	70.3 (24.1)	69.5 (22.8)

3. Secondary Outcome

Title	Behavioral Expression of Trust on the Trust Game
Description	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.
Time Frame	Pre & post a 12 week treatment group

Outcome Measure Data

Analysis Population Description

Veterans with PTSD under 50 years of age

Arm/Group Title	CPT-C	Treatment-as-Usual
Arm/Group Description	Participants in group CPT-C Group CPT-C: Participants who chose to participate in a 12-week CPT-C treatment group.	Participants who chose to participate in a 12-week treatment as usual group and offered CPT-C group treatment after 12 weeks.
Measure Participants	18	20
Pre-Treatment Investment Ratio	.31 (.17)	.34 (.23)
Post-Treatment Investment Ratio	.37 (.27)	.28 (.25)

4. Secondary Outcome

Title	PTSD Checklist (PCL)
Description	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.
Time Frame	Administered each week at weekly group sessions or pre-post treatment as usual

Outcome Measure Data

Analysis Population Description

Veterans under 50 years of age diagnosed with PTSD

Arm/Group Title	CPT-C	Treatment-as-Usual
Arm/Group Description	Participants in group CPT-C Group CPT-C: Participants who chose to participate in a 12-week CPT-C treatment group.	Participants who chose to participate in a 12-week treatment as usual group and offered CPT-C group treatment after 12 weeks.
Measure Participants	18	19
Pre-Treatment PCL-M Scores	65.33 (11.0)	56.83 (17.1)
Post-Treatment PCL-M Scores	58.37 (13.48)	59.53 (11.88)

Adverse Events

Arm/Group Title	CPT-C		Treatment-as-Usual
Arm/Group Description	Participants in group CPT-C 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.		Participants randomly assigned to the Waitlist Control Group (who will participate in CPT-C after 12 weeks).
All Cause Mortality
	CPT-C		Treatment-as-Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CPT-C		Treatment-as-Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	CPT-C		Treatment-as-Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/23 (0%)

Limitations/Caveats

This is a pilot study based on a small sample of Veterans with PTSD.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.