Neuromodulation and Neuroimaging in Older Children With Mild Traumatic Brain Injury

NCT05762796 | Recruiting FDA Device

• 2 other identifiers: STUDY00006696UL1TR001412
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Mild traumatic brain injury (mTBI) often causes persistent motor and cognitive deficits in children resulting in functional limitations. We are testing a brain stimulation method along with evaluating objective tools to help record and restore communication among affected brain areas, which will facilitate recovery in youth after mTBI.

Conditions

Motor Disorders; Cognitive Impairment; Brain Concussion; Mild Traumatic Brain Injury

Keywords

Brain Concussion; Mild Traumatic Brain Injury; Child; Motor Activity; Cognitive Impairment; Transcranial Direct Current Stimulation; Neuroimaging

Outcome Measures

Primary Outcomes (5)

• Changes in the Revised Physical and Neurological Examination of Subtle Signs (PANESS - Gaits and Stations Measures)

  The PANESS is used to assess static and dynamic postural stability of adolescents. The PANESS contains nine static and dynamic balance tasks: 1) walking on heels, 2) walking on toes, 3) walking on sides of feet, 4) double-legged stance, 5) single-legged stance for 30 seconds, 6) tandems stance for 20 seconds, 7) forward tandem walking, 8) backward tandem walking, and 9) hopping in place on one foot. The scores from all tasks are combined to form an aggregated score.

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

• Changes in the Nine-Hole Peg Test

  The test consists of a square board with 9 holes. The participants are asked to pick up pegs one at a time and place them into holes as quickly as possible. The participants are then instructed to remove the pegs one by one from the board and put them back into the container. The average time from four trials is examined to arrive at the total score.

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

• Changes in the Dual-Task Screen

  It consists of a gait task and an eye-hand coordination task. In the single gait task condition, participants are instructed to walk as quickly as possibly for 6 meter and step over a 1.5 meter obstacle placed 4 meter from the start. In the dual gait condition, participants will repeat the gait task while counting the months of the year backward. In the eye-hand coordination single task, participants will be instructed to stand 1.5 meter away from the wall and throw and catch a tennis ball for 30 seconds. In the dual task eye-hand coordination condition, the participants will repeat the catch and throw task while serially subtracting 3s from 100s. The difference between the single task and the dual task will be calculated to arrive at the score for each participant.

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

• Changes in Motor Control Test Measurements (Posturography)

  The motor control test (MCT) will be administered using the Posturography Machine to assess the ability of the patient to recover from translational disturbances of the support surface. The six conditions each participant will perform include three forward translations with small, medium, and large intensities as well as three backward translations with small, medium, and large intensities. Each participant go through three trials at each translation and intensity. The participant will be scored on latency; their ability to respond to the translation in milliseconds, and the amplitude scaling; the average amount of weight carried by each leg during the translation. An increased latency indicates impairment within the neural pathways that cause musculoskeletal problems in addition to central abnormalities. Abnormal amplitude scaling indicates inadequate or asymmetrical level of force exerted during the recovery from the support disturbance.

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

• Changes in resting-state functional magnetic resonance imaging outcome

  MRI scanning will be used to assess the functional connectivity among the brain areas involved in motor learning and motor planning. Functional connectivity will be measured by looking at differences in the control group and the experimental group.

  Day 2-5 (post initial behavioral testing), Day 26- 32 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -66 (final post-sham tDCS), and Day 94 - 96 (post 30-days follow up behavioral testing visit).

Secondary Outcomes (3)

• Changes in PHQ-8

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

• Changes in GAD-7

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

• Changes in WASI-II

  Day 1 (at the initial visit), Day 26- 30 (final post-anodal transcranial direct current stimulation (tDCS), Day 60 -64 (final post-sham tDCS), and Day 94 (at 30-days follow up visit).

Study Arms (2)

Healthy Controls

NO INTERVENTION

Never-concussed age-and gender-matched healthy controls will not receive any intervention. Behavioral and neuroimaging measurements will be administered only once, at the initial visit.

tDCS in Youth with mild traumatic brain injury

EXPERIMENTAL

Behavioral as well as neuroimaging measurements will be administered at the final post-anodal transcranial direct current stimulation (tDCS), final post-sham tDCS, and at 30-day follow-up visits. tDCS will be administered after the initial behavioral and neuroimaging testing. Ten sessions of 1.5 mA real tDCS and 10 sessions of sham tDCS will be administered using Neurocom (Germany) DC stimulator and two 5x7 electrodes, moistened in saline solution, to 10 participants with mTBI following a cross-over design with a 2-week washout period. The location of the brain regions will be determined using either the Transcranial Magnetic Stimulation Neuronavigation or Brainsight Neuronavigation system. The anode will be placed over pre-determined brain regions, whereas the cathode will be placed either over Fp2 (contralateral supraorbital) or other suitable reference areas.

Device: tDCS in Youth with mild traumatic brain injury

Interventions

tDCS in Youth with mild traumatic brain injury DEVICE

The safety and tolerability of tDCS have been established in children with mTBI (1). A recent study of 13-18 year youths post-mTBI showed that three sessions of 1.5 mA anodal tDCS over the left DLPFC, positively influenced prolonged working memory deficits. (2) Additionally, rodent studies show the effectiveness of tDCS in improving cognitive-motor (motor planning and balance/gait) function in rats with mTBI. (3)

tDCS in Youth with mild traumatic brain injury

Eligibility Criteria

• Age: 10 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• age 10-15 years at enrollment
• enrolled after 6 weeks of mTBI injury
• exhibiting post-concussive symptoms (e.g., difficulty planning, sequencing, and executing a motor action)
• Sustained an mTBI or concussion within the past 12 months
• Parent and child proficient in English
• Healthy Controls Cohort:
• to 15 years old
• no concussion history
• Parent and child proficient in English
• Experimental Cohort:

You may not qualify if:

• loss of consciousness \> 30 minutes
• post-traumatic amnesia \> 24 hours
• intracranial findings on clinical imaging
• history of developmental delay
• history of learning disability or ADHD
• Sustained a lower limb or upper limb injury that has not healed
• History of Seizures
• Noticeable skin lesions/burns or any other severe skin problems at the site of the electrodes before the start of the stimulation.
• Parent/guardian report metal implants anywhere in the head/ncek/body on the MRI screening form (see attached).
• Parent/guardian report shrapnel/bullets in the body on the MRI screening form.
• Parent/guardian report any electronic implant such as a cardiac pacemaker, cochlear implant, ventricular shunt, cardiac defibrillator, aneurysm clips, pacing wires, any implant held in place with a magnet, heart valve, or deep brain stimulator on the MRI screening form.
• Parent/guardian report a craniotomy or any other surgery in the past 6 weeks on the MRI screening form.
• Parent/guardian report being claustrophobic on the MRI screening form.
• Parent/guardian report and provide orbit x-ray after the eye injury involving a metal that the subject is cleared as indicated on the MRI screening form.
• Pregnant females as reported by parent/guardian on the pre-consent screening form. Pubertal/post-pubertal female participants14 and above will be provided a separate post-consent screening form at each MRI visit to ensure the female reports accurately without fear.

Sponsors & Collaborators

• State University of New York at Buffalo: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Ghazala Saleem

Buffalo, New York, 14214, United States

RECRUITING

Related Publications (4)

• Saleem GT, Crasta JE, Slomine BS, Cantarero GL, Suskauer SJ. Transcranial Direct Current Stimulation in Pediatric Motor Disorders: A Systematic Review and Meta-analysis. Arch Phys Med Rehabil. 2019 Apr;100(4):724-738. doi: 10.1016/j.apmr.2018.10.011. Epub 2018 Nov 7.

  PMID: 30414398 BACKGROUND

• Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol. 2011 Sep;14(8):1133-45. doi: 10.1017/S1461145710001690. Epub 2011 Feb 15.

  PMID: 21320389 BACKGROUND

• Rotter J, Kamat D. Concussion in Children. Pediatr Ann. 2019 Apr 1;48(4):e182-e185. doi: 10.3928/19382359-20190326-01.

  PMID: 30986320 BACKGROUND

• Fregni F, Nitsche MA, Loo CK, Brunoni AR, Marangolo P, Leite J, Carvalho S, Bolognini N, Caumo W, Paik NJ, Simis M, Ueda K, Ekhitari H, Luu P, Tucker DM, Tyler WJ, Brunelin J, Datta A, Juan CH, Venkatasubramanian G, Boggio PS, Bikson M. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin Res Regul Aff. 2015 Mar 1;32(1):22-35. doi: 10.3109/10601333.2015.980944.

  PMID: 25983531 BACKGROUND

MeSH Terms

Conditions

Brain Concussion; Motor Disorders; Cognitive Dysfunction; Motor Activity

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Ghazala Saleem, EdD

  State University of New York at Buffalo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ghazala Saleem, EdD

CONTACT

716-829-2589; GHAZALAS@BUFFALO.EDU

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The Aim 1 of the study uses a cross-sectional design. The behavioral and neuroimaging data will be collected in one or two separate visits. The Aim 2 \& Aim 3 of the study use a cross-over design. The data will be collected in either twenty-three or twenty-four visits.

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: March 10, 2023
• Study Start: February 20, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: MRI data will become available after the study is finished. Data will be available indefinitely.
• Access Criteria: Data can be accessed through Center for Brain Imaging database after written approval.

Locations

US (1)