Combined Neuromodulation and Cognitive Training for Post-mTBI Depression

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: Recruiting
• Conditions: Depression; Mild Traumatic Brain Injury; Concussion, Brain
• Intervention / Treatment: Device: iTBS; Behavioral: Personalized, Augmented Cognitive Training (PACT); Device: sham iTBS

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michelle Schy; Phone Number: 858-642-3848; Email: mschy@health.ucsd.edu
• Study Contact Backup: Name: Janae Wyckoff; Phone Number: 858-642-3848; Email: jwyckoff@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • UCSD
      • Contact: Michelle Schy; Phone Number: 858-642-3848; Email: mschy@health.ucsd.edu
      • Contact: Janae Wyckoff; Phone Number: 858-642-3848; Email: jwyckoff@health.ucsd.edu

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Time Frame
Hamilton Rating Scale for Depression	change over 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Health Questionnaire-9		change over 8 weeks
Neurobehavioral Symptom Inventory		change over 8 weeks
PTSD Checklist for DSM-5		change over 8 weeks
Headache Impact Test		change over 8 weeks
Pittsburgh Sleep Quality Index		change over 8 weeks
WHO Disability Assessment Schedule		change over 8 weeks
Glasgow Outcome Scale - Extended		change over 8 weeks
PROMIS Cognitive Function Abilities Short Form		change over 8 weeks
Patient Global Impression of Change	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	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		change over 8 weeks
D-KEFS Color Word Interference Test		change over 8 weeks
WMS-IV Digit Span		change over 8 weeks
WAIS-IV Processing Speed		change over 8 weeks
Hopkins Verbal Learning Test - Revised		change over 8 weeks
UCSD Performance-Based Skills Assessment-Brief	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

• Sponsor: University of California, San Diego
• Collaborators: San Diego Veterans Healthcare System
• Investigators: Principal Investigator: Elizabeth Twamley, PhD, UC San Diego

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: rTMS; cognitive rehabilitation; neuromodulation; cognitive training; TMS; brain stimulation; transcranial magnetic stimulation; iTBS; TBS; theta burst stimulation
• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Behavioral Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Behavior; Depression; Brain Concussion
• Other Study ID 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