Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03316196 |
| Other study ID # |
MHBB-023-17S |
| Secondary ID |
CX001600-01A1 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 13, 2018 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
VA Office of Research and Development |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Posttraumatic stress disorder (PTSD) is a chronic, disabling condition that occurs in a
subgroup of individuals after experiencing traumatic stress, and is common in Veterans
seeking mental health treatment at the VA. Although evidence-based psychosocial treatments
exist for PTSD, a substantial portion of individuals do not fully respond to treatment. Thus,
there is a clear need to continue researching novel interventions for PTSD in Veterans.
Recently, new interventions for mental health disorders have utilized computerized cognitive
training techniques in order to improve the functioning of cognitive systems and reduce
symptoms. This type of intervention, often referred to as neurotherapeutics, may hold promise
for PTSD as a method for ameliorating symptoms and improving cognition. Individuals with PTSD
demonstrate difficulties with cognitive control functions, which appear to be causally
implicated in symptoms of the disorder (e.g., intrusive trauma-related memories). To date the
efficacy of neurotherapeutics for PTSD has been understudied in Veterans.
The current proposal aims to bridge research on basic neurocognitive mechanisms of PTSD with
intervention research by conducting a randomized controlled trial (RCT) of a cognitive
control training program in 80 Veterans with PTSD. Veterans will complete computer-based
training exercises designed to specifically target and improve aspects of cognitive control.
Veterans will complete the program twice per week for eight weeks. Symptoms will be assessed
before and after treatment, as well as at a two month follow up time point. The primary goal
of the study is to examine the effect of the intervention on PTSD symptoms and cognitive
deficits. Evaluating symptom change as a result of the intervention will provide critical
data regarding the utility of this program as a PTSD treatment. If effective, this training
program could serve as alternative treatment option for Veterans with PTSD, and could be
translated into an easily transportable intervention for dissemination (e.g., through
web-based platforms). A secondary goal is to use functional magnetic resonance imaging (fMRI)
to better understand the mechanisms by which cognitive training culminates in symptom
reduction. If training cognitive control with neurotherapeutics directly enhances functioning
of specific neural substrates as hypothesized, improvements in affective processes relying on
shared neural regions would also be predicted. Modifying functioning in these substrates with
training may thus reduce symptoms by improving neural functioning while processing and
managing trauma-related affect and information. Neural systems used for cognitive control
targeted in the training described (e.g., dorsolateral prefrontal cortex [dlPFC]) are also
recruited when individuals mentally manipulate emotional information, such as when
individuals use reappraisal to change the way that they think about negative emotional
situations or content. In this study, Veterans will complete a neutral cognitive control task
and a reappraisal task while undergoing fMRI before and after completing the training
treatment. This will be the first study to evaluate neurobiological mechanisms of this type
of training in PTSD, which is a fundamental next step for understanding how to improve the
training program and who may be best served by completing it.
Description:
Posttraumatic Stress Disorder (PTSD) is one of the most prevalent service-related mental
health conditions in treatment-seeking Veterans, yet even gold standard interventions are not
universally effective. Veterans would be greatly served by development of novel intervention
approaches for PTSD, particularly those could be easily transportable. The emerging field of
neurotherapeutics, which uses computerized training techniques to modulate cognitive
processing, is one such approach that has shown promise for improving cognitive and emotional
symptoms in mental health disorders. The current proposal represents the first effectiveness
study of a cognitive control training intervention for reducing PTSD symptoms in Veterans,
with a goal of exploring neurobiological mechanisms of affective and cognitive generalization
of training effects.
PTSD is characterized by deficits in "top-down" cognitive control abilities, as evidenced by
neuropsychological findings of poor executive functioning and neurobiological evidence of
diminished prefrontal cortical activity coupled with exaggerated limbic activity. Cognitive
control deficits are causally implicated in re-experiencing symptoms, suggesting that
cognitive control may be a novel and effective treatment target. The investigator developed a
cognitive control training intervention that has demonstrated initial evidence of efficacy in
civilian women with PTSD secondary to sexual assault. However, the effects of this program in
Veteran participants and the precise neurocognitive mechanisms of symptom reduction in the
intervention remain poorly understood. If training cognitive control directly enhances
functioning of specific cognitive systems that are causally implicated in the etiology of
emotional and cognitive symptoms, treatment-related improvements in affective symptoms and
neuropsychological performance within the trained domain would be predicted. From a
neurobiological perspective, training cognition is thought to operate via modification of
specific neural substrates, suggesting that training effects should generalize to affective
processes relying on shared neural regions. One such affective process is reappraisal (i.e.,
generating different ways of thinking about emotional content in order to regulate emotion),
which requires cognitive control over affective emotional information, and depends on brain
circuits identified as key cognitive control regions (e.g., dorsolateral prefrontal cortex,
dlPFC). PTSD is characterized by aberrant affective and neurobiological patterns during
reappraisal that likely contribute to persistent re-experiencing and hyperarousal symptoms.
Training may reduce symptoms by improving neural functioning of cognitive control regions
during affective control processes (e.g., reappraisal) that are critical to managing
trauma-related affect.
In this proposal, the applicant's prior clinical trials research experience will be
integrated with new mentoring in functional neuroimaging (fMRI) to facilitate identification
of treatment-related symptom and neural change following cognitive control training. Bridging
research on basic neurocognitive mechanisms of PTSD with intervention research in this way
will ultimately facilitate precise neurotherapeutic treatment development and personalization
techniques. In this randomized controlled trial (RCT), 80 Veterans with PTSD will be assigned
to the cognitive control training program developed by the applicant (intervention condition:
COGnitive ENhancement Training [COGENT]), or a minimal cognitive control program (sham
training condition [ST]) completed twice week for 8 weeks. The COGENT training program
requires participants to repeatedly utilize specific cognitive control functions (i.e.,
interference control) in the context of a modified working memory capacity task, with the
goal of improving performance through implicit, practice-based learning. The primary outcome
will be PTSD symptom reduction, and cognitive generalization will be assessed with a brief
neuropsychological assessment. To evaluate changes in the neural bases proposed to underlie
COGENT, participants will undergo fMRI while completing two cognitive control tasks
(affectively neutral and emotionally balanced) before and after treatment. Assessments will
occur at baseline, post-treatment, and at follow-up.
Aim 1: To examine the effects of the training program on PTSD and neurocognitive symptoms in
Veterans. PTSD symptoms will be measured using the Clinician Administered PTSD Scale (CAPS)
interview and neurocognitive functioning will be assessed with Delis Kaplan Executive
Functioning System subtests. Individuals completing COGENT are hypothesized to show a)
greater reduction in PTSD re-experiencing symptoms and b) improved neurocognitive performance
relative to those in ST over time. Exploratory aims will also examine changes in PTSD
diagnostic status across groups.
Aim 2: To examine neurobiological changes in COGENT versus ST during neutral and affective
cognitive control tasks. Neurobiological response to treatment will be assessed using fMRI
during cognitive control tasks (one affectively neutral working memory capacity task and one
affectively balanced reappraisal task with negative emotional information). Individuals
completing the COGENT program are predicted to demonstrate increased neural activation of
dlPFC and anterior cingulate regions from pre- to post-training during the tasks. Exploratory
aims will evaluate corresponding physiological change during the affective fMRI task and the
utility of fMRI neural functioning at baseline for predicting treatment response.
