Combined Neuromodulation and Cognitive Training for Post-mTBI Depression

• Sponsor: University of California, San Diego (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05682677
• Collaborator: San Diego Veterans Healthcare System (U.S. Fed)
• Enrollment: 72
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 39
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Depression; Mild Traumatic Brain Injury; Concussion, Brain	Device: iTBS; Device: sham iTBS; Behavioral: Personalized, Augmented Cognitive Training (PACT)	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Combined Neuromodulation and Cognitive Training for Post-mTBI Depression
• Anticipated Study Start Date: Apr 1, 2023
• Anticipated Primary Completion Date: Jun 30, 2026
• Anticipated Study Completion Date: Jun 30, 2026

Arms and Interventions

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)	Device: sham iTBS; sham iTBS over the left dorsolateral prefrontal cortex; Behavioral: Personalized, Augmented Cognitive Training (PACT); 6 sessions of PACT

Outcome Measures

Primary Outcome Measures

1. Hamilton Rating Scale for Depression [change over 8 weeks]

Secondary Outcome Measures

1. Patient Health Questionnaire-9 [change over 8 weeks]

2. Neurobehavioral Symptom Inventory [change over 8 weeks]

3. PTSD Checklist for DSM-5 [change over 8 weeks]

4. Headache Impact Test [change over 8 weeks]

5. Pittsburgh Sleep Quality Index [change over 8 weeks]

6. WHO Disability Assessment Schedule [change over 8 weeks]

7. Glasgow Outcome Scale - Extended [change over 8 weeks]

8. PROMIS Cognitive Function Abilities Short Form [change over 8 weeks]

9. Patient Global Impression of Change [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 [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 [change over 8 weeks]

12. D-KEFS Color Word Interference Test [change over 8 weeks]

13. WMS-IV Digit Span [change over 8 weeks]

14. WAIS-IV Processing Speed [change over 8 weeks]

15. Hopkins Verbal Learning Test - Revised [change over 8 weeks]

16. UCSD Performance-Based Skills Assessment-Brief [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD	La Jolla	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego
• San Diego Veterans Healthcare System

Investigators

• Principal Investigator: Elizabeth Twamley, PhD, UC San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elizabeth Twamley, Professor of Psychiatry, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT05682677
• Other Study ID Numbers: W81XWH-22-2-0045
• First Posted: Jan 12, 2023
• Last Update Posted: Jan 12, 2023
• Last Verified: Jan 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Elizabeth Twamley, Professor of Psychiatry, University of California, San Diego: brain stimulation; neuromodulation; transcranial magnetic stimulation; theta burst stimulation; TMS; TBS; rTMS; iTBS; cognitive training; cognitive rehabilitation
• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Depression; Depressive Disorder

Study Results

No Results Posted as of Jan 12, 2023