Post-Traumatic Stress DisordersNCT06629064
Cognitive Control Training for Extinction in PTSD
A study testing Working Memory Training in people with Post-Traumatic Stress Disorders and Stress Disorders, Traumatic, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The proposed study will test whether a working memory training (WMT) program improves fear extinction learning and its underlying neural circuitry in Veterans with posttraumatic stress disorder (PTSD). WMT is designed to improves the ability to maintain task-relevant information in mind. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post-Traumatic Stress Disorders, Stress Disorders, Traumatic, Post Traumatic Stress Disorder
- What is being tested?
- Working Memory Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2024to 30 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fluent in English
- Meet current DSM-5 criteria for Posttraumatic Stress Disorder
- Are willing to attend 8 total remote sessions of working memory training over course of four weeks
- Are willing to attend MRI scans pre and post working memory training
- 4-week stability on pharmacological and psychosocial treatments
Who cannot join
- A lifetime history of psychotic disorders, lifetime history of bipolar disorder
- Past-year severe substance use and severe alcohol use disorder. Mild-to-moderate alcohol use disorder will be allowed to enhance generalizability in our sample due to the high comorbidity of alcohol use and PTSD
- History of any neurological disorder that might be associated with cognitive dysfunction (e.g., cerebrovascular accident, intracranial surgery, aneurysm, seizure disorder)
- Acute suicidality requiring immediate clinical intervention
- Moderate to severe traumatic brain injury (TBI). However, mild to moderate levels of TBI (mTBI) will be included
- Receiving benzodiazepines or medications with anticholinergic effects that may affect fear learning measures
- Inability to safely complete fMRI session (i.e., metal in body, medical implants)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002
Daniel M Stout, PhD, (858) 642-3944, Daniel.Stout@va.gov
Daniel M Stout, PhD
About this study
Official title: Identifying Clinically Relevant Neural Circuit Mechanisms of Cognitive Control Training for PTSD
The proposed study will test whether a working memory training (WMT) program improves fear extinction learning and its underlying neural circuitry in Veterans with posttraumatic stress disorder (PTSD). WMT is designed to improves the ability to maintain task-relevant information in mind. The project will further validate the relationship between working memory and fear extinction using novel computational and multivariate analyses that link to specific PTSD symptoms. If WMT can enhance fear extinction learning, then WMT may be a powerful adjunctive treatment that can enhance exposure therapy outcomes or be leveraged as a stand-alone treatment. This project supports the Department of Veteran Affairs mission of developing viable targets of treatment for Veterans with PTSD.
Read the detailed description
Posttraumatic stress disorder (PTSD) is prevalent, debilitating, and associated with significant levels of functional impairment in Veterans seeking care at the VA. Despite evidence that current treatments for PTSD are effective, a substantial portion of individuals maintain elevated PTSD symptoms after first line treatments. Mechanistic insight and tools that improve the neurocognitive and affective mechanisms that underlie successful clinical outcomes from evidence-based psychotherapies, like prolonged exposure, are highly needed. One of the most prominent mechanisms associated with therapeutic symptom reduction in PTSD is fear extinction. Indeed, extinction learning is a key theoretical treatment target in exposure-based therapies for PTSD. Fear extinction learning is not only an emotional process, but relies on an individual's cognitive control abilities, including working memory (WM). Under a WM framework, high WM ability offers the ability of an individual to adjudicate the competition between threat and extinction memory expression as they repeatedly encounter feared cues that are no longer threatening. Consistent with this hypothesis, previous investigations show replicable findings that variation in WM ability is associated with laboratory measures of fear extinction learning. The investigators have previously shown that psychophysiological and neural measures of fear extinction is a construct malleable to treatment. In civilian populations a brief WM training (WMT) designed to boost WM was effective in reducing anxiety during a speech exposure and was is effective in enhancing behavioral and neural markers of WM ability. These findings raise the intriguing possibility for the mechanistic link between WM and extinction, and that enhancing WM ability through WMT may also improve fear extinction learning success in Veterans with PTSD.
The current proposal aims to answer these questions. In a between-group design, Veterans diagnosed with PTSD will complete 8-sessions of working memory training (WMT) or sham-training (ST) over a four-week period. At pre- and post-training, Veterans will complete a standard fear acquisition \& extinction learning task in addition to tasks assaying WM capacity and cognitive control. The investigators will identify whether WMT modulates behavior, psychophysiological, and neural changes in extinction learning. The investigators will further test the conceptual link between WM and extinction in Veterans with PTSD by testing whether neural circuits associated with high WM capacity and extinction learning are linked. The project is expected to determine if a cognitive control training program targeting WM capacity shows the potential to enhance behavioral and neural markers of fear extinction, mechanisms that are clearly integral to current PTSD treatments. These aims support the VA mission of testing and evaluating innovative treatment targets for PTSD. Results will provide a mechanistic foundation for future clinical trials that test whether adding WMT prior to or in conjunction with exposure based psychotherapies will improve clinical outcomes and further clarify existing mechanistic and neurobiological models of PTSD and its treatment for Veterans.
- Conditions
- Post-Traumatic Stress Disorders, Stress Disorders, Traumatic, Post Traumatic Stress Disorder, PTSD, Trauma and Stressor Related Disorders
- Being tested
- Working Memory Training, Sham Training
- Keywords
- Trauma and Stressor Related Disorders, PTSD, cognitive training, working memory, Fear Extinction
- Medical subject headings
- Stress Disorders, Post-Traumatic, Stress Disorders, Traumatic, Trauma and Stressor Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Working Memory TrainingBehavioural
Also called WMT
Computer-administered working memory training program. WMT is a modified working memory capacity task designed to train working memory functioning. WMT is designed to contain high interference across trials and is adaptive to performance. As participants improve working memory, the task becomes more difficult.
Sham TrainingOther
Also called Sham
The Sham condition requires participants to complete a similar computer task for the same length of time. The Sham Training is a modified working memory capacity task designed to place less demands on working memory.
| Study group | Role | What they receive |
|---|---|---|
| Working Memory Training | Experimental | Computer-administered working memory training program. WMT is a modified working memory capacity task designed to train working memory functioning. WMT is designed to contain high interference across trials and is adaptive to performance. As participants improve working memory, the task becomes more difficult. Receives: Behavioral: Working Memory Training |
| Sham Training | Sham comparator | The Sham condition requires participants to complete a similar computer task for the same length of time. The Sham Training is a modified working memory capacity task designed to place less demands on working memory. Receives: Other: Sham Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Behavioral Threat Expectancy Ratings During Extinction Performance
Threat Expectancy Ratings. Behavioral ratings will be collected during the extinction learning task. Responses will be on scale of 1- 4. High scores reflect greater threat expectancy. It is expected that the working memory training group (WMT) will have lower threat expectancy ratings during extinction learning than the Sham group.
Measured: Baseline, Approximately 5 or 6 weeks
Extinction Electrodermal Activity Response
Electrodermal Activity Response. Responses are measured in microsiemens and time-locked to the CS+ trials during extinction learning. It is expected that the working memory training group (WMT) will have lower electrodermal activity responses during extinction learning than the Sham group.
Measured: Baseline, Approximately 5 or 6 weeks
Extinction Blood Oxygen Level Dependent (BOLD) Response
Functional Magnetic Resonance Imaging (fMRI) will be used to measure Blood Oxygen Level Dependent (BOLD) Response during the Extinction task. BOLD response during the extinction task conditions are measured using % signal change from baseline BOLD activity with higher scores indicating greater activation. It is expected that the working memory training group (WMT) will have greater changes in BOLD responses during extinction learning than the Sham group.
Measured: Baseline, Approximately 5 or 6 weeks
Secondary outcomes (5)
Working Memory Task Blood Oxygen Level Dependent (BOLD) Response
Functional Magnetic Resonance Imaging (fMRI) will be used to measure Blood Oxygen Level Dependent (BOLD) Response during a working memory capacity task while undergoing functional MRI. BOLD response to the task conditions is measured using % signal change with higher scores indicating greater activation.
Measured: Baseline, Approximately 5 or 6 weeks
Working memory capacity change detection task
This behavioral task measures the number of visual items maintained in working memory and is a measure of working memory capacity. This task will use simple geometric shapes as stimuli. Scores are measured using percent accuracy (o - 100%) and a measure of working memory capacity (K-score range: 0 - 6 in this task). High scores indicate greater accuracy and working memory capacity.
Measured: Baseline, Approximately 5 or 6 weeks
Affective working memory task
An affective working memory task. A behavioral task, the affective working memory task measures working memory capacity - how many stimuli are stored in working memory) and include conditions with an emotional distractors. Scores are measured using percent accuracy (range: 0-100%) and a measure of working memory capacity (K-score range: 0 - 2 in this task). High scores indicate greater accuracy and working memory capacity. Reaction time (in milliseconds) will also be collected. High Reaction time indicates slower or more impaired working memory ability.
Measured: Baseline, Approximately 5 or 6 weeks
Flanker Task
This behavioral task measures cognitive and motor inhibition. Stimuli consist of arrows presented at the center of a computer screen. Reaction Time (in milliseconds) for button presses will be the primary variable. High scores indicate slower reaction time to make the required behavioral response. The investigators will also measure accuracy, with high scores indicating higher accuracy and will be scored as percent correct (range: 0-100%)
Measured: Baseline, Approximately 5 or 6 weeks
Affective stop signal task
This behavioral task measures cognitive and motor inhibitory control and will include affective stimuli. Primary outcome variables will be reaction time (in milliseconds) and accuracy (0 to 100%). High reaction time indicates slow inhibitory control on stop signal trials.
Measured: Baseline, Approximately 5 or 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2024
- Study start1 Oct 2024
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Traumatic Stress DisordersStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two group randomized controlled trial of WMT versus a Sham training
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Daniel M Stout, PhD, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06629064
- Sponsor's protocol ID
- MHBP-001-23F
- Other IDs
- 1I01CX002760
- Status last verified
- Oct 2026
- First submitted
- 2 Oct 2024
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identifying Clinically Relevant Neural Circuit Mechanisms of Cognitive Control Training for PTSD
- ClinicalTrials.gov ID
- NCT06629064
- Acronym / sponsor ID
- MHBP-001-23F
- Conditions
- Post-Traumatic Stress Disorders, Stress Disorders, Traumatic, Post Traumatic Stress Disorder, PTSD, Trauma and Stressor Related Disorders
- Keywords
- Trauma and Stressor Related Disorders, PTSD, cognitive training, working memory, Fear Extinction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 8 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study will test whether a working memory training (WMT) program improves fear extinction learning and its underlying neural circuitry in Veterans with posttraumatic stress disorder (PTSD). WMT is designed to improves the ability to maintain task-relevant information in mind. The project will further validate the relationship between working memory and fear extinction using novel computational and multivariate analyses that link to specific PTSD symptoms. If WMT can enhance fear extinction learning, then WMT may be a powerful adjunctive treatment that can enhance exposure therapy outcomes or be leveraged as a stand-alone treatment. This project supports the Department of Veteran Affairs mission of developing viable targets of treatment for Veterans with PTSD.
Detailed description
Posttraumatic stress disorder (PTSD) is prevalent, debilitating, and associated with significant levels of functional impairment in Veterans seeking care at the VA. Despite evidence that current treatments for PTSD are effective, a substantial portion of individuals maintain elevated PTSD symptoms after first line treatments. Mechanistic insight and tools that improve the neurocognitive and affective mechanisms that underlie successful clinical outcomes from evidence-based psychotherapies, like prolonged exposure, are highly needed. One of the most prominent mechanisms associated with therapeutic symptom reduction in PTSD is fear extinction. Indeed, extinction learning is a key theoretical treatment target in exposure-based therapies for PTSD. Fear extinction learning is not only an emotional process, but relies on an individual's cognitive control abilities, including working memory (WM). Under a WM framework, high WM ability offers the ability of an individual to adjudicate the competition between threat and extinction memory expression as they repeatedly encounter feared cues that are no longer threatening. Consistent with this hypothesis, previous investigations show replicable findings that variation in WM ability is associated with laboratory measures of fear extinction learning. The investigators have previously shown that psychophysiological and neural measures of fear extinction is a construct malleable to treatment. In civilian populations a brief WM training (WMT) designed to boost WM was effective in reducing anxiety during a speech exposure and was is effective in enhancing behavioral and neural markers of WM ability. These findings raise the intriguing possibility for the mechanistic link between WM and extinction, and that enhancing WM ability through WMT may also improve fear extinction learning success in Veterans with PTSD.
The current proposal aims to answer these questions. In a between-group design, Veterans diagnosed with PTSD will complete 8-sessions of working memory training (WMT) or sham-training (ST) over a four-week period. At pre- and post-training, Veterans will complete a standard fear acquisition \& extinction learning task in addition to tasks assaying WM capacity and cognitive control. The investigators will identify whether WMT modulates behavior, psychophysiological, and neural changes in extinction learning. The investigators will further test the conceptual link between WM and extinction in Veterans with PTSD by testing whether neural circuits associated with high WM capacity and extinction learning are linked. The project is expected to determine if a cognitive control training program targeting WM capacity shows the potential to enhance behavioral and neural markers of fear extinction, mechanisms that are clearly integral to current PTSD treatments. These aims support the VA mission of testing and evaluating innovative treatment targets for PTSD. Results will provide a mechanistic foundation for future clinical trials that test whether adding WMT prior to or in conjunction with exposure based psychotherapies will improve clinical outcomes and further clarify existing mechanistic and neurobiological models of PTSD and its treatment for Veterans.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Two group randomized controlled trial of WMT versus a Sham training
| Arm | Type | Receives |
|---|---|---|
| Working Memory Training | Experimental | Behavioral: Working Memory TrainingComputer-administered working memory training program. WMT is a modified working memory capacity task designed to train working memory functioning. WMT is designed to contain high interference across trials and is adaptive to performance. As participants improve working memory, the task becomes more difficult. |
| Sham Training | Sham comparator | Other: Sham TrainingThe Sham condition requires participants to complete a similar computer task for the same length of time. The Sham Training is a modified working memory capacity task designed to place less demands on working memory. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Fluent in English
- Meet current DSM-5 criteria for Posttraumatic Stress Disorder
- Are willing to attend 8 total remote sessions of working memory training over course of four weeks
- Are willing to attend MRI scans pre and post working memory training
- 4-week stability on pharmacological and psychosocial treatments
Key exclusion criteria (7 listed)
- A lifetime history of psychotic disorders, lifetime history of bipolar disorder
- Past-year severe substance use and severe alcohol use disorder. Mild-to-moderate alcohol use disorder will be allowed to enhance generalizability in our sample due to the high comorbidity of alcohol use and PTSD
- History of any neurological disorder that might be associated with cognitive dysfunction (e.g., cerebrovascular accident, intracranial surgery, aneurysm, seizure disorder)
- Acute suicidality requiring immediate clinical intervention
- Moderate to severe traumatic brain injury (TBI). However, mild to moderate levels of TBI (mTBI) will be included
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Working Memory TrainingAlso: WMTComputer-administered working memory training program. WMT is a modified working memory capacity task designed to train working memory functioning. WMT is designed to contain high interference across trials and is adaptive to performance. As participants improve working memory, the task becomes more difficult. | Behavioural | Working Memory Training |
| Sham TrainingAlso: ShamThe Sham condition requires participants to complete a similar computer task for the same length of time. The Sham Training is a modified working memory capacity task designed to place less demands on working memory. | Other | Sham Training |
Primary outcome
Behavioral Threat Expectancy Ratings During Extinction Performance
Time frame: Baseline, Approximately 5 or 6 weeks
Threat Expectancy Ratings. Behavioral ratings will be collected during the extinction learning task. Responses will be on scale of 1- 4. High scores reflect greater threat expectancy. It is expected that the working memory training group (WMT) will have lower threat expectancy ratings during extinction learning than the Sham group.
Extinction Electrodermal Activity Response
Time frame: Baseline, Approximately 5 or 6 weeks
Electrodermal Activity Response. Responses are measured in microsiemens and time-locked to the CS+ trials during extinction learning. It is expected that the working memory training group (WMT) will have lower electrodermal activity responses during extinction learning than the Sham group.
Extinction Blood Oxygen Level Dependent (BOLD) Response
Time frame: Baseline, Approximately 5 or 6 weeks
Functional Magnetic Resonance Imaging (fMRI) will be used to measure Blood Oxygen Level Dependent (BOLD) Response during the Extinction task. BOLD response during the extinction task conditions are measured using % signal change from baseline BOLD activity with higher scores indicating greater activation. It is expected that the working memory training group (WMT) will have greater changes in BOLD responses during extinction learning than the Sham group.
5 secondary outcomes
Working Memory Task Blood Oxygen Level Dependent (BOLD) Response
Time frame: Baseline, Approximately 5 or 6 weeks
Working memory capacity change detection task
Time frame: Baseline, Approximately 5 or 6 weeks
Affective working memory task
Time frame: Baseline, Approximately 5 or 6 weeks
Flanker Task
Time frame: Baseline, Approximately 5 or 6 weeks
Affective stop signal task
Time frame: Baseline, Approximately 5 or 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel M Stout, PhD principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Working Memory Training in people with Post-Traumatic Stress Disorders and Stress Disorders, Traumatic, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel M Stout, PhD ((858) 642-3944, Daniel.Stout@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Behavioral Threat Expectancy Ratings During Extinction Performance (time frame: Baseline, Approximately 5 or 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.