Rehabilitation of Executive Functioning in Veterans With PTSD and Mild TBI
Phase: NA
Conditions: Post Traumatic Stress Disorder, Mild Traumatic Brain Injury, Concussion
Sponsor: VA Office of Research and Development

Rehabilitation of Executive Functioning in Veterans with PTSD and Mild TBI 
 
Study ID: D1111-I 
 
ClinicalTrials.gov ID: NCT01921179 
 
Protocol Abstract for 2019 Continuing Review of PTSD-mTBI Study 
03/26/2019 
 
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Instructions: Include a 1-5 page (do not exceed 5 pages) abstract containing the 
following content (as applicable).  Please attach a separate PDF document.  
 
Purpose 
The overall aim of this proposal is to investigate the potential short and long term 
effectiveness of a cognitive training program 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 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 
 
Research questions and Hypotheses 
Question 1: What are short and long term effects of GOALS training on neuro-cognitive 
performance in Veterans with co-morbid PTSD and Mild TBI? 
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Hypothesis 1:  Participants in GOALS training will demonstrate greater 
improvements on untrained standardized neuropsychological measures of 
complex attention and executive function compared to participants in EDU 
training.   
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Hypothesis 2: At the six month follow-up, participants will on average 
demonstrate improvements on standardized neuropsychological measures of 
complex attention and executive function relative to their baseline performance, 
suggesting persistence of GOALS training benefits. 
Question 2: What are short and long term effects of GOALS training in veterans with co-
morbid PTSD and Mild TBI on complex real-life functional task performance and daily 
functioning ? 
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Hypothesis 1: Participants who participate in GOALS training will demonstrate 
greater improvements on an untrained complex real-life functional task than 
participants who participate in control EDU training. 
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Hypothesis 2: Participants who participate in GOALS training will report greater 
improvements on self report measures of functional performance in their daily 
lives compared to participants who participate in control EDU training. 
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Hypothesis 3: Training benefits will persist six months post GOALS training, as 
measured by participants’ improvements in complex functional task performance 
and on self-report measures of everyday functional performance, relative to their 
pre-GOALS performance 

Question  3: What are short and long term effects of GOALS training in veterans with co-
morbid PTSD and Mild TBI on self-report measures of emotional regulation? 
Hypothesis 1: Participants who participate in GOALS cognitive training will report 
greater improvements on self report measures of emotional regulation compared 
to participants who participate in control EDU training. 
Hypothesis 2: At six month follow-up, participants will demonstrate improvements 
on self report measures of emotional regulation relative to their pre-GOALS 
performance, suggesting persistence of training benefits. 
Methods 
Eligibility criteria  
Inclusion criteria: Veterans, ages 18 to 75 years, with at least 12 years of education, a 
current diagnosis of PTSD (DSM IV-R), and a history of mild traumatic brain injury, 
defined by the American Congress of Rehabilitation Medicine (ACRM) and VA, as a 
traumatically-induced physiological disruption of brain function. 
Exclusion Criteria: History of moderate or severe TBI (defined by ACRM as 
having an injury that includes a loss of consciousness  lasting longer than 30 
minutes, or post-traumatic amnesia lasting longer than 24 hours). Unstable 
medical, neurologic, or psychiatric condition, including severe cognitive 
dysfunction, or other reasons for being unable or unwilling to participate in the 
training and assessments; ongoing illicit drug or alcohol abuse (AUDIT>8); 
psychosis, severe depression, anxiety or PTSD precluding participation in 
research activities; current evidence-based PTSD remediation therapy; and, poor 
English comprehension.  
 
Interventions 
Participants who meet the inclusion criteria will be enrolled in the study and randomized 
to either five week Brain Health Education (EDU) or Goal-Oriented Attentional Self-
regulation (GOALS) training. After 5 weeks, those who enter with EDU will receive 5 
weeks of GOALS, while those who begin with GOALS will have no further formal training. 
Both groups will participate in assessments at baseline, week 5 and week 10. Long-term 
follow-up will be conducted at 6 months.  
The GOALS training involves ten 2 hour sessions of group-based training, three 
individual 1 hour training sessions, and approximately 20 hours of home practice. It is 
conducted in a small group format with 2-5 participants, and 2 therapists per group.  
The GOALS intervention emphasizes two key components: First, regulation of 
distractibility (redirection of attention to goal-relevant processes and the filtering of non-
relevant ‘noise’, especially in the context of distractions) is addressed with attention 
regulation training. Training emphasizes principles of applied mindfulness-based 
attention regulation to redirect cognitive processes towards goal-relevant activities even 
when distracted. Second, these goal-oriented attentional self-regulation skills are 
practiced in daily life and actively applied to self-generated complex goals. Participants 
are asked to identify personally-relevant and feasible functional goals as individual and 
group projects. They are then trained in applying the goal management strategies on the 
functional task(s) of their choice. The main objective is to allow extensive practice and 
application of skills, thereby linking the attentional regulation directly to goal attainment 
efforts. 

The EDU training is an active comparison matched with GOALS for therapist time, for 
homework load, and participation in a group. It involves ten 2 hour sessions of group-
based training, three individual 1 hour training sessions, and approximately 20 hours of 
home practice. It is conducted in a small group format with 2-5 participants and 2 
therapists per group. The EDU training is designed to be engaging and provide 
information about brain functioning and brain health. 
 
Assessments 
At baseline (pre GOALS or EDU), week 5, week 10 (post GOALS for those who began 
with EDU), and at 6 months, participants will be evaluated with a multi-level battery of 
measures assessing:  
1. Neuro-cognitive performance focusing on neuropsychological measures of 
complex attention, executive function and memory.  
2. Functional performance on complex ‘real-life‘ tasks involving multitasking and 
goal management 
3. Emotional regulation and daily functioning.  
 
Neuropsychological Assessment: The neuropsychological battery used in this study was 
developed to assess performance in cognitive domains of complex attention and 
executive function that are commonly affected by both TBI and PTSD and targeted by 
GOALS training. Working Memory will be assessed with (1) Letter Number Sequencing, 
WAIS IV and (2) Auditory Consonant Trigrams. Sustained attention will be assessed with 
the timed Digit Vigilance test. Inhibition of Automatic Responding will be assessed with 
DKEFS Stroop Inhibition (time and error score). Mental Flexibility will be assessed with:  
(1) Trails B and (2) DKEFS Stroop Inhibition-Switching. Performance on verbal memory 
tests will be assessed with Hopkins Verbal Learning Test - HVLT-R.  
 
Participants’ performance in cognitive domains commonly affected by TBI and PTSD, 
but not targeted by the intervention, will also be assessed as a marker of potential non-
specific changes. Processing speed will be assessed with (1) Trails A, requiring rapidly 
connecting in order numbers on a page, and with (2) DKEFS Stroop Color Naming and 
(3) DKEFS Stroop Word Reading.  Intellectual functions estimate will be assessed at 
baseline with Wechsler Test of Adult Reading- WTAR. The purpose of the WTAR is to 
estimate pre-morbid intellectual ability. The overall battery of neurocognitive tests will 
take approximately 1 hour. 
 
Functional Assessment: To address the functional and ecological limitations of 
conventional clinical neuropsychological tests in characterizing executive dysfunction, 
we included functional assessments in the neurobehavioral test battery. Participants will 
complete complex ‘real-life’ functional assessment task using the Goal Processing Scale 
(GPS). To control for practice effects of repeated administrations GPS has three 
alternate forms. The GPS domains assessed include: Planning, Initiation, Maintenance 
of Attention, Self-Monitoring, Sequencing and Switching Attention, Flexible Problem 
Solving, Memory, and Execution. 
 
The evaluator will videotape the GPS functional assessment if the subject agreed and 
signed the VA 10-3203 Consent form and continues to agree to being videotaped during 
the assessment. The subject has the option to refuse this without affecting participation 
in the study. 
 

Self-Report Measures: Emotional regulation / mood disturbance measures will include 
Profile of Mood States, Clinician-Administered PTSD Scale (CAPS), PTSD Checklist-
Military Version (PCL-M), and Difficulties in Emotional Regulation Scale. Daily 
Functioning measures will include: Mayo Portland Adaptability Inventory and Goal 
Processing Questionnaire (GPQ). 
 
Follow-up 
At 6 months post-baseline, participants will be re-evaluated with the above-described 
multi-level battery of measures. 
 
Data Safety Monitoring Plan  
All information will be kept confidential in accordance with all regulations as specified by 
the Department of Veterans Affairs. Any injuries that are a direct result of research 
procedures will be treated at no cost to the participant. Any adverse events will be 
reported immediately by the PI to the Central VA. All associated personnel will have 
human subjects training and certification. All patients will be given a copy of their 
informed consent and encouraged to ask questions if they have any concerns. 
 
Cognitive Testing: There is a possibility of frustration from poor performance or fatigue. 
Cognitive testing will stop if a patient displays frustration or appears tired.   
Cognitive training: There is a possibility of fatigue, frustration, or boredom from 
performance of cognitive tasks. Participants are allowed frequent breaks during training. 
For patients, training will be adjusted for the fatigue level, and training sessions will stop 
if patients are frustrated or fatigued. Thus far, participants have generally expressed 
positive experiences with training.    
It is possible that participation in the study may lead to an exacerbation of PTSD 
symptoms. All research staff directly working with participants have previous training and 
experience in working with this Veteran population (e.g., neuropsychologists; 
neuropsychology trainees; occupational therapist, certified rehabilitation counselor, etc.). 
Additionally, prior to contact with subjects, all research staff will undergo investigator-led 
training to confirm they recognize symptoms associated with PTSD/mTBI, such as 
subject reports of, or behavior that reflects: re-experiencing the traumatic event, 
avoidance, increased anxiety, emotional arousal, anger and irritability. Research staff 
will be instructed to communicate such manifestations as soon as possible to the study 
investigators, who are licensed clinicians with expertise in the assessment and 
management of symptoms associated with PTSD and brain injury. A study investigator 
will immediately attempt to contact the subject for a telephone assessment, or if 
indicated, to schedule an in-person assessment. Further action will be based on an 
assessment of the subject. Possible actions may include referral for additional 
appropriate clinical evaluation and/or follow-up treatment and possibly terminating the 
subject’s participation in the study. If a subject is withdrawn from the study due to 
increased symptoms, the study investigator will personally inform the subject of the 
decision to terminate involvement and may refer the subject to follow-up treatment if the 
subject is significantly distressed over being withdrawn. 
In the event a subject manifests increased PTSD symptoms that are not minor and 
transient, the investigator will complete Form 119: Report of Unanticipated Serious 
Adverse Event (SAE) and/or Unanticipated Problem (UAP) Involving Risks to 

Participants or Others.  
If a subject expresses concern about another subject divulging personal information 
outside the research setting, research staff will inform the study investigator. The study 
investigator will then contact the subjects in question to address any breaches of privacy 
or confidentiality. 
Research staff will notify the study investigator within 24 hours if any subjects report or 
manifest more than minor and transient distress. The study investigator will contact the 
subject to evaluate the situation and determine if clinical referral is warranted. If a 
referral is warranted, the study investigator will inform the subject that a referral for 
treatment will be made. When making the referral, the study investigator will request that 
the subject’s privacy be respected when scheduling the appointment. 
All research staff will be trained in the above procedures. The research team will also 
meet or have conference calls weekly to discuss study activities and any issues or 
concerns about subjects. The research staff at both study sites is the same. 
Progress to date 
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Study was conducted at both SFVAMC and VA NCHCS in Martinez sites. 
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Staff was hired and trained in study recruitment, assessment and cognitive 
training procedures. 
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Study actively recruited subjects at both sites: 
o 545 letters describing the study have been mailed to potential 
participants; 218 detailed telephone screens have been conducted; 
76 participants have been enrolled. 
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To help enhance recruitment, researchers has made extensive efforts to enroll 
Veterans, including providing IRB-approved recruitment material to VA 
Outpatient clinics, Veteran Centers, State of California Department of 
Rehabilitation Veteran services programs, State of California Employment 
Development Department disabled Veterans outreach, State of California County 
Veterans services, community college Veteran affairs offices.  
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Presentations describing the aims of this study have been made by PI and co-
investigators  to clinicians and researchers at both SFVAMC and VA NCHCS in 
Martinez, and at the:  VINS21 TBI Polytrauma  meeting 2014, 2015, 2016; and 
2018; American College of Rehabilitation Medicine Conference October 2015; 
VA Psychology Leadership Conference May 2015 and May 2017; 10 World 
Congress on Brain Injury in April 2017; International Neuropsychological Society 
Meeting February 2016 ,February 2017, February 2018 and February 2019; 8th 
Federal Interagency Conference June 2018, and American Psychological 
Association Conference August 2018.  
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Study is closed for enrollment, last follow-up on 12/30/18. Data analysis has 
started. 
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Preliminary results from 40 participants who completed the training indicate that 
at week 5, after GOALS training, but not after EDU training, participants 
significantly improved on neuropsychological measures of attention/executive 
function, complex functional task performance and measures of emotional 
regulation. Participants reported incorporating trained strategies into their daily 
lives.