Rehabilitation of Executive Functioning in Veterans With PTSD and Mild TBI

• ClinicalTrials.gov Identifier: NCT01921179
• Recruitment Status: Completed
• First Posted: August 13, 2013
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

One of the most pressing concerns within the VA currently is the provision of interventions that address the cognitive as well as emotional problems faced by Veterans with concurrent mild TBI and PTSD. One purpose of this study is to learn more about how PTSD and mild brain injury influences how people think, act, and feel. This may include how people pay attention, keep information in memory, organize plans for achieving important goals, and manage stress. Another purpose of this research is to learn more about the effects of cognitive training on the thinking, behavior, and emotions of individuals with PTSD and mild brain injury - both in the short- and long-term. With this research, the investigators hope to better understand and treat cognitive and emotional difficulties that can occur due to PTSD and mild brain injury.

Condition or disease	Intervention/treatment	Phase
Post Traumatic Stress Disorder; Mild Traumatic Brain Injury, Concussion	Behavioral: GOALS (Goal-Oriented Attentional Regulation); Behavioral: EDU (Brain Health Education)	Not Applicable

Detailed Description:

The overall aim of this proposal is to investigate the potential short and long term effectiveness of a cognitive training program Goal-Oriented Attentional Self-regulation (GOALS) that targets executive control functions in Veterans with co-morbid posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (mTBI), and cognitive difficulties. Both PTSD and a history of mild TBI are prevalent in Veterans from the Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) conflicts, with reported rates for each disorder ranging from 14 - 22%. Both PTSD and TBI have been associated with cognitive dysfunction which may lead to functional impairment and poor community reintegration. PTSD can be highly debilitating not only due to emotional dysregulation, but also due to deficits in the cognitive control processes.

Goal-Oriented Attentional Self-Regulation (GOALS) is a therapist administered cognitive rehabilitation training that targets executive control functions of applied mindfulness-based attention regulation and goal management, and links them to participant-defined real-life goals. In a prior study with individuals with chronic brain injury, this training has improved cognitive performance in areas of complex attention / executive function, memory, complex functional task performance, and daily functioning. Furthermore, functional MRI results after training indicated significantly enhanced modulation of neural processing in extrastriate cortex and changes in prefrontal cortex. Preliminary results from a recently completed study with Veterans with a history of chronic TBI also support improvements post GOALS on neuropsychological measures of attention and executive function, performance on complex 'real-life' tasks, and self-report measures of functional performance. Furthermore, participants also showed improvement on the emotional regulation self-report measures. These findings suggest that improving cognitive control may also improve functioning in other domains such as emotional regulation and functional performance in daily life.

In a randomized, controlled intervention study design, 42 Veterans with a diagnosis of PTSD, history of mTBI and residual cognitive difficulties will participate in experimental (GOALS), and/or active comparison (Brain Health Education - EDU) interventions matched for time and intensity. Participants will be randomized to start with either 5 weeks of GOALS or EDU training. Those who begin with EDU will cross-over to GOALS, while those begin with GOALS will have 5 weeks of self-driven practice only. Both groups will participate in pre and post intervention measurements at baseline, weeks 5 and 10. Long-term follow-up will be at 6 months. Pre- and post-intervention measurements will include performance on untrained: neuro-cognitive tests assessing targeted and non-targeted cognitive domains, complex functional task performance in low structure 'real-world' setting, and self-report measures of emotional regulation and daily functioning.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Rehabilitation of Executive Functioning in Veterans With PTSD and Mild TBI
• Actual Study Start Date: July 31, 2013
• Actual Primary Completion Date: December 30, 2018
• Actual Study Completion Date: December 30, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: GOALS (Goal-Oriented Attentional Regulation); Goal-Oriented Attentional Regulation (GOALS) will involve 5-weeks of training (20 hours of group training (2 hour sessions, 2 days per week), 3 hours of individual training (1 hour at the beginning, halfway through and at the end of training), and approximately 20 hours of home practice). Some subjects will only receive the GOALS intervention.	Behavioral: GOALS (Goal-Oriented Attentional Regulation); Goal-Oriented Attentional Regulation (GOALS) will involve 5-weeks of training (20 hours of group training (2 hour sessions, 2 days per week), 3 hours of individual training (1 hour at the beginning, halfway through and at the end of training), and approximately 20 hours of home practice). Some subjects will only receive the GOALS intervention.
Active Comparator: EDU (Brain Health Education); Brain Health Education (EDU) will involve 5-weeks of training (20 hours of group training (2 hour sessions, 2 days per week), 3 hours of individual training (1 hour at the beginning, halfway through and at the end of training), and approximately 20 hours of homework). The EDU intervention involves education on brain health and functioning in a classroom format, with study materials for homework. Some subjects will start with EDU and then cross-over to the GOALS.	Behavioral: EDU (Brain Health Education); Brain Health Education (EDU) will involve 5-weeks of training (20 hours of group training (2 hour sessions, 2 days per week), 3 hours of individual training (1 hour at the beginning, halfway through and at the end of training), and approximately 20 hours of homework). The EDU intervention involves education on brain health and functioning in a classroom format, with study materials for homework. Some subjects will start with EDU and then cross-over to the GOALS.; Other Name: EDU

Outcome Measures

Primary Outcome Measures :

1. Change in Performance on Neurocognitive Measure of Attention and Executive Function Post GOALS Intervention vs EDU Control Training [ Time Frame: baseline, 5 weeks ]

   Attention and Executive Function Overall Domain Z Score (primary neuropsychological outcome measure) is calculated as the average of z scores of following tests: Letter Number Sequencing, Auditory Consonant Trigrams, Digit Vigilance, Trails B, DKEFS Stroop Inhibition, DKEFS Stroop Inhibition-Switching, DKEFS Verbal Fluency Switching, DKEFS Visual Fluency Switching.

   (The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the population mean. Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population)

2. Long Term Follow-up After GOALS Training - Change in Performance on Neurocognitive Measures of Attention and Executive Function 6+ Months Post GOALS Intervention Relative to Baseline [ Time Frame: baseline, 6+ months after GOALS training ]

   Attention and Executive Function Overall Domain Z Score (primary neuropsychological outcome measure) is calculated as the average of z scores of following tests: Letter Number Sequencing, Auditory Consonant Trigrams, Digit Vigilance, Trails B, DKEFS Stroop Inhibition, DKEFS Stroop Inhibition-Switching, DKEFS Verbal Fluency Switching, DKEFS Visual Fluency Switching.

   (The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the population mean. Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population)

Secondary Outcome Measures :

1. Change in Performance on Complex Functional Task -Goal Processing Scale Post GOALS Intervention vs EDU Control Training [ Time Frame: baseline; 5 weeks ]
   Goal Processing Scale Overall Performance score (Primary functional performance outcome ) is calculated as the average of the 8 sub-domain scores including: Planning, Initiation, Maintenance of Attention, Self-Monitoring, Sequencing and Switching Attention, Flexible Problem Solving, Memory, and Execution. Minimum value is 0, maximum value is 10. Higher scores indicate better outcome.
2. Long Term Follow-up After GOALS Training - Change in Performance on Complex Functional Task -Goal Processing Scale 6+ Months Post GOALS Intervention Relative to Baseline [ Time Frame: baseline, 6 months post GOALS training ]
   Goal Processing Scale Overall Performance score (Primary functional performance outcome ) is calculated as the average of the 8 sub-domain scores including: Planning, Initiation, Maintenance of Attention, Self-Monitoring, Sequencing and Switching Attention, Flexible Problem Solving, Memory, and Execution. Minimum value is 0, maximum value is 10. Higher scores indicate better outcome
3. Change on Self Report Measures of Emotional Regulation GOALS Post Intervention vs EDU Control Training [ Time Frame: baseline, 5 weeks ]

   Overall psychological distress will be assessed with Profile of Mood States (POMS) questionnaire Total Mood Disturbance Z Score (primary emotional regulation outcome measure).

   (The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the population mean. Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population)

4. Long Term Follow-up Change on Self Report Measures of Emotional Regulation 6+ Months Post GOALS Intervention [ Time Frame: baseline, 6 months ]

   Overall psychological distress is assessed with Profile of Mood States (POMS) questionnaire Total Mood Disturbance Z Score (primary emotional regulation outcome measure)

   (The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the population mean. Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of PTSD
• History of mild TBI, including concussion > 6 months ago
• Cognitive difficulties affecting daily functioning
• Age 18-75
• Veteran
• At least 12th grade education or equivalent

Exclusion Criteria:

• Amnesic/Severe memory problems
• Active Substance Abuse/Dependence
• Medical condition that may affect mental status/disrupt study participation
• Active psychotropic medication changes
• Participation in evidence-based PTSD treatment

Contacts and Locations

Locations

United States, California

Martinez Outpatient Clinic and Community Living Center, Martinez, CA

Martinez, California, United States, 94553

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States, 94121

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Tatjana Novakovic-Agopian, PhD; San Francisco VA Medical Center, San Francisco, CA

  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:

Study Protocol and Statistical Analysis Plan: Full Protocol  [PDF] November 13, 2014

Informed Consent Form  [PDF] November 18, 2014

Study Protocol: Study Protocol Summary Abstract  [PDF] March 26, 2019

More Information

Publications of Results:

Novakovic-Agopian T, Chen AJ, Rome S, Abrams G, Castelli H, Rossi A, McKim R, Hills N, D'Esposito M. Rehabilitation of executive functioning with training in attention regulation applied to individually defined goals: a pilot study bridging theory, assessment, and treatment. J Head Trauma Rehabil. 2011 Sep-Oct;26(5):325-38. doi: 10.1097/HTR.0b013e3181f1ead2.

Chen AJ, Novakovic-Agopian T, Nycum TJ, Song S, Turner GR, Hills NK, Rome S, Abrams GM, D'Esposito M. Training of goal-directed attention regulation enhances control over neural processing for individuals with brain injury. Brain. 2011 May;134(Pt 5):1541-54. doi: 10.1093/brain/awr067. Epub 2011 Apr 22.

Novakovic-Agopian T, Chen AJ, Rome S, Rossi A, Abrams G, D'Esposito M, Turner G, McKim R, Muir J, Hills N, Kennedy C, Garfinkle J, Murphy M, Binder D, Castelli H. Assessment of subcomponents of executive functioning in ecologically valid settings: the goal processing scale. J Head Trauma Rehabil. 2014 Mar-Apr;29(2):136-46. doi: 10.1097/HTR.0b013e3182691b15.

Novakovic-Agopian T, Kornblith E, Abrams G, Burciaga-Rosales J, Loya F, D'Esposito M, Chen AJW. Training in Goal-Oriented Attention Self-Regulation Improves Executive Functioning in Veterans with Chronic Traumatic Brain Injury. J Neurotrauma. 2018 Dec 1;35(23):2784-2795. doi: 10.1089/neu.2017.5529. Epub 2018 Jul 23.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01921179
• Other Study ID Numbers: D1111-I
• First Posted: August 13, 2013
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Following study completion and publication of results we will explore available mechanisms for data sharing

• 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:

Post Traumatic Stress Disorder,; Mild Traumatic Brain Injury; Concussion; Cognitive Rehabilitation

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Trauma and Stressor Related Disorders; Mental Disorders; Head Injuries, Closed; Wounds, Nonpenetrating