Personalized Brain Stimulation to Treat Chronic Concussive Symptoms

NCT06073886 | Recruiting Phase 2 DMC FDA Device

• 1 other identifier: TP210602
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to investigate a new treatment for chronic symptoms after concussion or mild traumatic brain injury in people aged 18-65 years old. Chronic symptoms could include dizziness, headache, fatigue, brain fog, memory difficulty, sleep disruption, irritability, or anxiety that occurred or worsened after the injury. These symptoms can interfere with daily functioning, causing difficulty returning to physical activity, work, or school. Previous concussion therapies have not been personalized nor involved direct treatments to the brain itself. The treatment being tested in the present study is a noninvasive, personalized form of brain stimulation, called transcranial magnetic stimulation (TMS). The investigators intend to answer the questions:

1. 1.Does personalized TMS improve brain connectivity after concussion?
2. 2.Does personalized TMS improve avoidance behaviors and chronic concussive symptoms?
3. 3.Do the improvements last up to 2 months post-treatment?
4. 4.Are there predictors of treatment response, or who might respond the best?
5. 5.One for the baseline symptom assessments and magnetic resonance imaging (MRI)
6. 6.Ten for TMS administration
7. 7.Three for post-treatment symptom assessments and MRIs

Conditions

Post-Concussion Syndrome; Concussion, Brain; Mild Traumatic Brain Injury; Head Injury; Headache; Dizziness; Cognitive Symptom; Dysautonomia; Anxiety; Irritability; Syndrome; Depression; Post-traumatic Stress Disorder

Keywords

Transcranial Magnetic Stimulation; Magnetic Resonance Imaging; Functional MRI; Personalized neuromodulation; Amygdala; Prefrontal Cortex

Outcome Measures

Primary Outcomes (4)

• Central target engagement, modulation, and durability

  Using resting-state functional magnetic resonance connectivity in the target frontoamygdala circuit

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

• Peripheral target engagement, modulation, and durability

  Using heart rate variability as measured by electrocardiogram

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

• Persistent post-concussive symptoms modulation and durability

  Using the Modified Rivermead Post Concussion Symptoms Questionnaire where higher scores are worse. Scores range from 0-64.

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

• Fear avoidance modulation and durability

  Using the Fear Avoidance Behavior Questionnaire for Traumatic Brain Injury where higher scores are worse. Scores range from 0-48.

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

Secondary Outcomes (3)

• Nightly Sleep Score from Oura Ring

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

• Daily heart rate variability

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

• Weekly avoidance behavior

  Change from baseline across all subsequent time points until completion of the study, an average of 4 months

Study Arms (3)

Active continuous theta-burst stimulation (cTBS) plus exposure

EXPERIMENTAL

10 days of active, continuous theta-burst stimulation (cTBS) will be delivered to a personalized region of the ventromedial prefrontal cortex (vmPFC) based on baseline brain circuit mapping for each individual participant.

Device: Active cTBS; Behavioral: Imaginal exposure

Inactive/Sham continuous theta-burst stimulation (cTBS) plus exposure

SHAM COMPARATOR

10 days of inactive, or sham, continuous theta-burst stimulation (cTBS) will be delivered to a personalized region of the ventromedial prefrontal cortex (vmPFC) based on baseline brain circuit mapping for each individual participant.

Device: Inactive/Sham cTBS; Behavioral: Imaginal exposure

Active Comparator continuous theta-burst stimulation (cTBS) plus exposure

ACTIVE COMPARATOR

10 days of active, continuous theta-burst stimulation (cTBS) will be delivered to a personalized region of the ventromedial prefrontal cortex (vmPFC) based on baseline brain circuit mapping for each individual participant.

Device: Active cTBS; Behavioral: Imaginal exposure

Interventions

Active cTBS DEVICE

600 active cTBS pulses will be delivered continuously (3 pulses at 50 hertz (Hz), repeated at 5 Hz, 15 pulses/sec, continuously for 40 seconds) twice/day for 1,200 pulses/day. The MagVenture MagPro active/sham system will be used to enable double blinding by universal serial bus (USB) key in which a current will be delivered through surface electrodes on the skin beneath the coil to mimic the sensory experience of cTBS for active and sham groups.

Active Comparator continuous theta-burst stimulation (cTBS) plus exposure; Active continuous theta-burst stimulation (cTBS) plus exposure

Inactive/Sham cTBS DEVICE

600 inactive, or sham, cTBS pulses will be delivered continuously (3 pulses at 50 hertz (Hz), repeated at 5 Hz, 15 pulses/sec, continuously for 40 seconds) twice/day for 1,200 pulses/day. The MagVenture MagPro active/sham system will be used to enable double blinding by universal serial bus (USB) key in which a current will be delivered through surface electrodes on the skin beneath the coil to mimic the sensory experience of cTBS for active and sham groups.

Inactive/Sham continuous theta-burst stimulation (cTBS) plus exposure

Imaginal exposure BEHAVIORAL

Personalized recordings about participants' descriptions of triggering or neutral stimuli or activities

Active Comparator continuous theta-burst stimulation (cTBS) plus exposure; Active continuous theta-burst stimulation (cTBS) plus exposure; Inactive/Sham continuous theta-burst stimulation (cTBS) plus exposure

Eligibility Criteria

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

You may qualify if:

• Mild traumatic brain injury (mTBI) defined in accord with the World Health Organization criteria in the last 12 months
• age 18-65 at the time of the mTBI
• high burden of post-concussive symptoms defined as a score \>=20 on the Rivermead Post-Concussion Symptoms Questionnaire

You may not qualify if:

• objective neurologic deficits
• ongoing or prolonged (\>3 months) post-concussive symptoms from a prior mTBI within 2 years of the index injury
• history of transcranial magnetic stimulation (TMS) therapy
• contraindications for TMS or magnetic resonance imaging (MRI) (e.g., metallic implant other than dental, pacemaker)
• severe mental, physical, or medical problems that would impede participation or pose a risk for the planned intervention (e.g., liver, kidney, or heart disease, uncontrolled diabetes or hypertension, malignancy, psychosis, previous seizure, pregnancy)
• active alcohol or illicit drug abuse
• inability to speak and read English

Sponsors & Collaborators

• University of California, Los Angeles: lead
• United States Department of Defense: collaborator

Study Sites (1)

UCLA

Westwood, Los Angeles, California, 90095, United States

RECRUITING

Related Publications (1)

• Bickart KC, Olsen A, Dennis EL, Babikian T, Hoffman AN, Snyder A, Sheridan CA, Fischer JT, Giza CC, Choe MC, Asarnow RF. Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI. Front Rehabil Sci. 2023 Jan 4;3:1064215. doi: 10.3389/fresc.2022.1064215. eCollection 2022.

  PMID: 36684686 BACKGROUND

MeSH Terms

Conditions

Post-Concussion Syndrome; Brain Concussion; Craniocerebral Trauma; Headache; Dizziness; Neurobehavioral Manifestations; Autonomic Nervous System Diseases; Anxiety Disorders; Syndrome; Depression; Stress Disorders, Post-Traumatic

Interventions

Implosive Therapy

Condition Hierarchy (Ancestors)

Head Injuries, Closed; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Sensation Disorders; Mental Disorders; Disease; Pathologic Processes; Behavioral Symptoms; Behavior; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

Desensitization, Psychologic; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Kevin Bickart, MD/PhD

CONTACT

(818)392-4614; bickartlab@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: October 10, 2023
• Study Start: March 6, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

US (1)