Combined Neuromodulation and Cognitive Training for Post-mTBI Depression

April 27, 2026 updated by: Elizabeth Twamley, University of California, San Diego
The primary goal of this clinical trial is to evaluate whether Personalized Augmented Cognitive Training (PACT) plus intermittent theta burst stimulation (iTBS) is effective for treating depression in Service Members, Veterans, and civilians who have sustained a mild TBI. Participants will receive PACT plus 20 sessions of iTBS or sham iTBS over 4 weeks. Assessments will occur at baseline, 2 weeks, 4 weeks, and 8 weeks. Researchers will compare the PACT+iTBS group to the PACT+sham iTBS group to see if PACT+iTBS is associated with more depression improvement.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female
  2. All racial and ethnic groups
  3. Ages 18 to 65
  4. Military service members receiving treatment at NMCSD or civilians receiving treatment at UCSD Health
  5. History of mild TBI (as defined by the DoD/VA criteria used in conjunction with the OSU TBI-ID method) over 3 months prior to study entry
  6. Meets criteria for current Major Depressive Episode within the context of Major Depressive Disorder, per MINI
  7. Score of 18 or higher on the HAMD-17, indicating moderate to severe depressive symptoms
  8. Stable on psychiatric medications for 6 weeks, with no changes to psychiatric medications expected during the study period
  9. No contraindications to TMS (passes the TMS Adult Safety Screening questionnaire)
  10. No contraindications to MRI (passes MRI safety screening questionnaire)
  11. Able to commit to the treatment schedule
  12. Able to complete assessment procedures in English
  13. Intact decision-making capacity and ability to provide voluntary informed consent

Exclusion Criteria:

  1. History of moderate, severe, or penetrating TBI
  2. History of other neurological condition unrelated to TBI, including but not limited to: conditions associated with increased intracranial pressure; space occupying brain lesions; cerebral aneurysm; stroke; transient ischemic attack within past two years; Parkinson's disease; Huntington's disease; dementia; multiple sclerosis; history of brain surgery; epilepsy; seizure except those therapeutically induced by electroconvulsive therapy (ECT) or a febrile seizure of infancy
  3. Implanted medical devices including cardiac pacemaker, medication pump, aneurysm clip, shunt, stimulator, cochlear implant, electrodes, or any other metal object within or near the head (excluding the mouth) that cannot be safely removed
  4. Active manic or psychotic illness per MINI
  5. Current substance use disorder per MINI
  6. Current active suicidal or homicidal ideation
  7. Pregnant or intending to become pregnant within the study period; breastfeeding
  8. Other sensory conditions or illnesses precluding participation in assessments or treatment
  9. Current dose of lorazepam 2 mg or greater daily (or benzodiazepine equivalent) or any anticonvulsant due to the potential to limit iTBS efficacy
  10. Taking medication that lowers seizure threshold
  11. Previous failed treatment with rTMS, iTBS, or ECT
  12. Completed >4 sessions of cognitive rehabilitation within the last 3 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PACT+iTBS
Personalized, Augmented Cognitive Training (PACT; 6 sessions over 4 weeks) + intermittent theta burst stimulation (iTBS; 20 sessions over 4 weeks)
Device: iTBS
iTBS over the left dorsolateral prefrontal cortex
Behavioral: Personalized, Augmented Cognitive Training (PACT)
6 sessions of PACT
Sham Comparator: PACT+sham iTBS
Personalized, Augmented Cognitive Training (PACT; 6 sessions over 4 weeks) + sham intermittent theta burst stimulation (sham iTBS; 20 sessions over 4 weeks)
Behavioral: Personalized, Augmented Cognitive Training (PACT)
6 sessions of PACT
Device: sham iTBS
sham iTBS over the left dorsolateral prefrontal cortex

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Hamilton Rating Scale for Depression
Time Frame: change over 8 weeks
change over 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Patient Health Questionnaire-9
Time Frame: change over 8 weeks
change over 8 weeks
Neurobehavioral Symptom Inventory
Time Frame: change over 8 weeks
change over 8 weeks
PTSD Checklist for DSM-5
Time Frame: change over 8 weeks
change over 8 weeks
Headache Impact Test
Time Frame: change over 8 weeks
change over 8 weeks
Pittsburgh Sleep Quality Index
Time Frame: change over 8 weeks
change over 8 weeks
WHO Disability Assessment Schedule
Time Frame: change over 8 weeks
change over 8 weeks
Glasgow Outcome Scale - Extended
Time Frame: change over 8 weeks
change over 8 weeks
PROMIS Cognitive Function Abilities Short Form
Time Frame: change over 8 weeks
change over 8 weeks
Patient Global Impression of Change
Time Frame: rating at 8 weeks
This measure asks the participant to rate their status since the start of the study from 1 (very much improved) to 7 (very much worse)
rating at 8 weeks
Traumatic Brain Injury Quality of Life
Time Frame: change over 8 weeks
The Traumatic Brain Injury Quality of Life The Traumatic Brain Injury Quality of Life measurement system (TBI-QOL) is a TBI-specific extension of the NIH PROMIS and Neuro-QoL measures that includes 20 items measuring physical, emotional, social, and cognitive domains
change over 8 weeks
D-KEFS Trail Making Test
Time Frame: change over 8 weeks
change over 8 weeks
D-KEFS Color Word Interference Test
Time Frame: change over 8 weeks
change over 8 weeks
WMS-IV Digit Span
Time Frame: change over 8 weeks
change over 8 weeks
WAIS-IV Processing Speed
Time Frame: change over 8 weeks
change over 8 weeks
Hopkins Verbal Learning Test - Revised
Time Frame: change over 8 weeks
change over 8 weeks
UCSD Performance-Based Skills Assessment-Brief
Time Frame: change over 8 weeks
The UCSD Performance-Based Skills Assessment-Brief is a performance-based measure that uses role play scenarios to assess capacity for financial and communication tasks.
change over 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Diego

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
San Diego Veterans Healthcare System

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Elizabeth Twamley, PhD, UC San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 19, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 4, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 12, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • W81XWH-22-2-0045

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD will be available via FITBIR.

IPD Sharing Time Frame

Following study completion; deidentified data available indefinitely.

IPD Sharing Access Criteria

Via FITBIR request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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