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NCT Number: NCT05682677

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.

Recruiting

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female
  • All racial and ethnic groups
  • Ages 18 to 65
  • Military service members receiving treatment at NMCSD or civilians receiving treatment at UCSD Health
  • 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
  • Meets criteria for current Major Depressive Episode within the context of Major Depressive Disorder, per MINI
  • Score of 18 or higher on the HAMD-17, indicating moderate to severe depressive symptoms
  • Stable on psychiatric medications for 6 weeks, with no changes to psychiatric medications expected during the study period
  • No contraindications to TMS (passes the TMS Adult Safety Screening questionnaire)
  • No contraindications to MRI (passes MRI safety screening questionnaire)
  • Able to commit to the treatment schedule
  • Able to complete assessment procedures in English
  • Intact decision-making capacity and ability to provide voluntary informed consent

Exclusion criteria

  • History of moderate, severe, or penetrating TBI
  • 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
  • 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
  • Active manic or psychotic illness per MINI
  • Current substance use disorder per MINI
  • Current active suicidal or homicidal ideation
  • Pregnant or intending to become pregnant within the study period; breastfeeding
  • Other sensory conditions or illnesses precluding participation in assessments or treatment
  • Current dose of lorazepam 2 mg or greater daily (or benzodiazepine equivalent) or any anticonvulsant due to the potential to limit iTBS efficacy
  • Taking medication that lowers seizure threshold
  • Previous failed treatment with rTMS, iTBS, or ECT
  • Completed >4 sessions of cognitive rehabilitation within the last 3 years

Treatment and study plan

iTBS

Device

iTBS over the left dorsolateral prefrontal cortex

Sham iTBS

Device

sham iTBS over the left dorsolateral prefrontal cortex

Personalized, Augmented Cognitive Training (PACT)

Behavioral

6 sessions of PACT

Primary outcomes

  1. Hamilton Rating Scale for Depression

    Time frame: change over 8 weeks

Secondary outcomes

  1. Patient Health Questionnaire-9

    Time frame: change over 8 weeks

  2. Neurobehavioral Symptom Inventory

    Time frame: change over 8 weeks

  3. PTSD Checklist for DSM-5

    Time frame: change over 8 weeks

  4. Headache Impact Test

    Time frame: change over 8 weeks

  5. Pittsburgh Sleep Quality Index

    Time frame: change over 8 weeks

  6. WHO Disability Assessment Schedule

    Time frame: change over 8 weeks

  7. Glasgow Outcome Scale - Extended

    Time frame: change over 8 weeks

  8. PROMIS Cognitive Function Abilities Short Form

    Time frame: change over 8 weeks

  9. 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)

  10. 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

  11. D-KEFS Trail Making Test

    Time frame: change over 8 weeks

  12. D-KEFS Color Word Interference Test

    Time frame: change over 8 weeks

  13. WMS-IV Digit Span

    Time frame: change over 8 weeks

  14. WAIS-IV Processing Speed

    Time frame: change over 8 weeks

  15. Hopkins Verbal Learning Test - Revised

    Time frame: change over 8 weeks

  16. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Janae Wyckoff

CONTACT

[email protected]

858-642-3848

Michelle Schy

CONTACT

[email protected]

858-642-3848

Sponsors and collaborators

Lead sponsor

University of California, San Diego

Other

Collaborators

  • San Diego Veterans Healthcare System

Registry information

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Jan 12, 2023
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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