Pilot Study of Neurofeedback for Photosensitivity in Mild Traumatic Brain Injury

Mild Traumatic Brain Injury Clinical Trial

Official title:

A Novel Neurofeedback Intervention for Photosensitivity in Mild Traumatic Brain Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06109909
• Other study ID #: C4374-P
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: November 30, 2025

Study information

• Verified date: January 2024
• Source: VA Office of Research and Development
• Contact: Francesca C Fortenbaugh, PhD
• Phone: (857) 364-4362
• Email: Francesca.Fortenbaugh[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to complete a pilot study testing the feasibility and acceptability of low-intensity pulse-based transcranial stimulation (LIP-tES) neurofeedback intervention for reducing photosensitivity symptoms in Veterans with a history of mild traumatic brain injury (mTBI). The study will also complete resting-state MRI scans to assess neurophysiological markers of photosensitivity and changes associated with LIP-tES intervention.

Description:

Photosensitivity (PS) is one of the more common sequelae of TBI, with over 50% of TBI patients reporting some level of PS in the acute and/or chronic stages. PS can range from mild to severe and can significantly impair social, physical, and cognitive functioning, as well as rehabilitation outcomes. While spectacle chromatic filters are conventionally used to alleviate symptoms, they are not designed to resolve issues with PS and have been associated with lower symptom recovery over time, underscoring the need to develop more effective, non-invasive treatment options that can reduce or eliminate PS. Recent work has shown that neurofeedback interventions, such as Low Intensity Pulse-Based Transcranial Electrical Stimulation (LIP-tES) may be effective in treating post-concussive symptoms and a preliminary case study from the investigators' research group suggests that LIP-tES may also be able to reduce PS symptoms in Veterans with a history of mild TBI. However, both the mechanism by which LIP-tES alters brain activity and alleviates symptoms across a range of disorders remains unclear as does the neurobiological basis of PS associated with mTBI and psychiatric comorbidities commonly seen in today's Veteran population. These knowledge gaps represent important limitations both for the clinical characterization of PS in Veterans and development/optimization of novel treatment options. This proposal will take an important first step in addressing these two important knowledge gaps. Aim 1: Complete a preliminary study testing the feasibility and acceptability of a novel LIP-tES intervention designed to reduce severity of PS in patients with a history of mTBI. Extending a recent case study completed by the investigators' research group, the investigators will complete a pilot study of LIP-tES for the treatment of PS in Veterans with a history of mTBI. The investigators will track recruitment capability (participants screened vs. enrolled, attrition rates and reasons for attrition), acceptability and suitability of the intervention, evaluate suitability of the sham procedure the investigators developed, and gain preliminary evaluation of participant responses to the intervention. Aim 2: Assess neurophysiological markers of PS and changes associated with LIP-tES intervention using resting-state fMRI. A subset of the participants will complete two MRI scans during the initial visit after the last LIP-tES or sham session. Preliminary work from the investigators' laboratory has identified a sparse connectome of regions that are predictive of moderate/severe PS ratings in a polymorbid sample of Veterans from the Translational Research Center for TBI and Stress Disorders (TRACTS) longitudinal cohort study. Extending this work, the investigators will test whether classification models using this previously identified connectome will correctly identify individuals who report a reduction in PS after treatment and whether connections are predictive of PS severity. By examining resting-state functional connectivity prior to and after completion of LIP-tES, the proposed study aims to increase the understanding of the underlying pathophysiological mechanisms of PS in mTBI and the mechanism by which LIP-tES may alleviate these symptoms.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Ages 18-65
• Documented history of mTBI at least 6 months prior to initial study visit
• Documented symptoms of photosensitivity
• Eye exam within the last 12 months documenting best-corrected acuity of 20/20 or better, normal pupillary function, color vision, no abnormalities on OCT scan, and normal Humphrey Visual Field test

Exclusion Criteria:

• History of strabismus or amblyopia
• Significant ocular media opacity that could reduce the amount of light entering the pupil in one or both eyes
• Previous or current history of retinal or optic nerve pathology in one or both eyes
• History of stroke and/or visual neglect
• History of neurodegenerative disease (e.g., Parkinson's, multiple sclerosis)
• History of epilepsy or seizures
• History of motor tics
• Current use of medications or substances that may severely affect pupillary response and/or increase photosensitivity
• Individuals with impaired decision-making capacity
• Illiterate or no English language proficiency

Related Conditions & MeSH terms

• Brain Concussion
• Brain Injuries
• Brain Injuries, Traumatic
• Mild Traumatic Brain Injury
• Photophobia
• Wounds and Injuries

Intervention

Device:
• Micro Current Neurofeedback Device using Low-Frequency Pulse-Based Transcranial Electrical Stimulation
The EEG interface device is a J&J Engineering 1-330 C2 box. The software used to determine LIP-tES feedback patterns was developed by Neurogen High Performance Neurofeedback. The EEG sampling frequency is 256 Hz on each of 2 EEG acquisition channels. The feedback LIP-tES is delivered via the 4 EEG leads (A+,A-,B+,B-), with respect to the Common Neck Reference. During each session, 2 electrodes (A- and B-) are attached to the participant's left and right mastoids, while the remaining two electrodes (A+ and B+) are moved to various locations on the scale to record EEG signals. All four (A+,A-,B+,B-) electrodes are involved in applying weak electrical pulses back to the brain (feedback process). The brief feedback pulse (~100mV) is adaptive and determined based on the offset of the frequency spectrum recorded across the left and right hemisphere (A vs. B) electrodes in the time window immediately prior to stimulation.

Locations

Country	Name	City	State
United States	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Utah Photophobia Symptom Impact Scale (UPSIS)	The UPSIS questionnaire is a 17-item questionnaire designed to quantitatively assess photosensitivity symptoms and their impact on activities of daily living. Scores range from 0-80 with higher values indicating more severe photosensitivity symptoms.	Baseline and again every two weeks through end of treatment, average of 6 weeks
Secondary	Stimulation Related Sensations Questionnaire (SRSQ)	The SRSQ will be administered to participants after the LIP-tES or sham session is complete. Results will be used to assess if participants report different sensations across conditions to examine if sham condition is appropriate control condition.	Baseline treatment visit
Secondary	Change from Baseline in Neurobehavioral Symptom Inventory (NSI)	The NSI will be administered as a measure of general post-concussive symptoms	Baseline and again at study completion, an average of 6 weeks
Secondary	Change from Baseline in Headache Impact Test (HIT-6)	The HIT-6 will be administered to measure changes in headache frequency and severity over prior month.	Baseline and again at study completion, an average of 6 weeks
Secondary	Qualitative Assessment of Study Recruitment Capability	Qualitative assessment of ability to recruit participants into the study by examining recruitment rates and reported obstacles to recruitment over study period. Assessment will result in decision that recruitment capabilities are suitable or unsuitable for additional study with no change to targeted population with same inclusion/exclusion criteria.	End of study data collection, approximately 2 years
Secondary	Qualitative Assessment of Acceptability of Data Collection Methods	Qualitative assessment of the suitability of data collection procedures by examining the retention and follow-up rates as the participants moved through the study and intervention, adherence rates to study procedures, barriers to study participation reported by participants over the course of the study. Assessment will result in decision that current study protocol is suitable or unsuitable for additional study with no change to study design.	End of study data collection, approximately 2 years
Secondary	Change from Baseline in PTSD Checklist for DSM-5 (PCL-5)	The PCL-5 will be administered to measure changes in PTSD symptom severity.	Baseline and again at study completion, an average of 6 weeks
Secondary	Change from Baseline in Depression, Anxiety, and Stress Scale (DASS)	The DASS questionnaire will be administered to measure changes in severity of depression, anxiety, and stress symptoms.	Baseline and again at study completion, an average of 6 weeks
Secondary	Change from Baseline in Pittsburgh Sleep Quality Index (PSQI)	The PSQI will be administered to provide a measure of changes in global sleep quality.	Baseline and again at study completion, an average of 6 weeks
Secondary	Change from Baseline in Short Form McGill Pain Questionnaire	This questionnaire will be administered to provide a general measure of changes in chronic pain.	Baseline and again at study completion, an average of 6 weeks