Cognitive Control Training for Extinction in PTSD

NCT06629064 | Recruiting

• 2 other identifiers: MHBP-001-23F1I01CX002760
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Baseline, Approximately 5 or 6 weeks

Secondary Outcomes (5)

• Working Memory Task Blood Oxygen Level Dependent (BOLD) Response

  Baseline, Approximately 5 or 6 weeks

• Working memory capacity change detection task

  Baseline, Approximately 5 or 6 weeks

• Affective working memory task

  Baseline, Approximately 5 or 6 weeks

• Flanker Task

  Baseline, Approximately 5 or 6 weeks

• Affective stop signal task

  Baseline, Approximately 5 or 6 weeks

Other Outcomes (4)

• PTSD Checklist for DSM-5 (PCL-5)

  Baseline, Approximately 5 or 6 weeks

• PHQ-9 (Patient Health Questionnaire-9)

  Baseline, Approximately 5 or 6 weeks

• General Anxiety Disorder 7 (GAD-7)

  Baseline, Approximately 5 or 6 weeks

Study Arms (2)

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.

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.

Other: Sham Training

Interventions

Working Memory Training BEHAVIORAL

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.

Also known as: WMT

Working Memory Training

Sham Training OTHER

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.

Also known as: Sham

Sham Training

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• week stability on pharmacological and psychosocial treatments

You may not qualify if:

• 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)

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Daniel M Stout, PhD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel M Stout, PhD

CONTACT

(858) 642-3944; Daniel.Stout@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Randomization will occur using a code corresponding to intervention arm. Participant and provider will not know the number-condition link.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Two group randomized controlled trial of WMT versus a Sham training

Study Record Dates

• First Submitted: October 2, 2024
• First Posted: October 8, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)