Do you have Epilepsy? Would you like to participate in a study using PhotoBioModulation (PBM)? PBM is being researched for potential benefits in resolving many stress-related brain disorders. It is a non-invasive technique that delivers light energy to cells and tissues that can promote brain stabilization and self-regulation, cell repair, reduce oxidative stress, and enhance cellular function. We ask you to participate for about 3-4 months and come to our facility for 30 minute sessions 3x a week for 15 weeks. You will receive extensive metabolic testing and an Õura ring for your participation.

WHO claims that epilepsy effects over 50 million people world-wide. First line treatment for seizures has been medication for well over 50 years with mixed results. There are many types of seizures, and the medications prescribed hope to target the type diagnosed, but while they may control the seizures to some effect, they also are riddled with side effects that create further duress. Other interventions may include surgery, vagal nerve stimulation (VNS) and other neurostimulation methodologies, diet and other lifestyle changes, and behavioral modification1. Comorbidities of epilepsy include anxiety, stroke, depression, ADHD, and possibly physical health compromises due to falling2. Stress often precipitates epileptic seizures, whether the syndrome is congenital, metabolic, electrophysiological, or environmental in nature3, 4.

Turner5 highlights a need for better interventions for this population, and the current proposal hopes to learn if photobiomodulation (PBM), a modern intervention which has shown promise in many syndromes, including anxiety, Parkinson's disease, pain and inflammation6 can reduce perceived stress, which in turns informs a healthier lifestyle for people with epilepsy (PWE) and reduce the effects of this disease. Since this intervention is quite new, few research projects have been published in this area.

Light is a fascinating phenomenon. Most people can identify color, and this is because of how it vibrates7. It's the vibration that causes us to feel warmed (yellows) or cooled (blues) since the speed of the vibration is stimulating neuronal communication. It's a brilliant innovation to use this property in photobiomodulation (PBM), which is the use of near-infra red light, as a clinical tool to enhance brain function on a cellular and chemical level. It is understood that what light therapy provides is a mitochondrial stimulatory mechanism that ultimately increases blood and cerebral spinal fluid (CSF) flow, cerebral oxygenation, and ATP production, as well as promote brain stabilization and self-regulation, and reduces inflammation8. It has been shown that the emitted light does, in fact, penetrate the skull and reach the desired cortical levels of the brain to facilitate the necessary mechanism to fulfill its goals9, 10.

The positive effects on mitochondrial health with PBM, and this interaction with epileptic brain behaviors11, as well as with neurodegenerative diseases12, 13, Parkinson's14, inflammation15, and TBI16 among others has been shown. In this study, we are primarily looking at if PBM can facilitate reduction of perceived stress in the PWE population. It is prudent to establish that we are not treating epilepsy because the device we're using is not FDA-cleared for brain-based procedures. However, current literature supports this, and present anecdotal evidence advises this intervention to be very successful and validates the proposed rigorous investigation.

The current study aims to use PBM to reduce stress in participants with epilepsy as a complementary therapeutic modality for improving quality of life and reducing suffering. PWE will be recruited to 4 clinical sites within the U.S. (Cincinnati, Houston, Miami, Warren, OH) and provided with PBM 3x/weekly for forty-five, 20-minute sessions, which may last between 15 and 20 weeks. They will have intake (T0), baseline (T1), mid (T2) post (T3) and 6-month follow-up (T4) assessment sessions in addition to the 45 PBM sessions.

The assessments include routine EEG recordings, the following metabolic testing: heavy metals & minerals, Enviro Complete, thyroid, anemia and lipid panels, HbA1c, CBC, c-reactive protein, vitamin D, homocysteine, OxLDL, F2-Isoprostane/Creatinine Ratio, Glutathione, basic metabolic panel, DutchPLUS panel, and OAT oxidative stress; the following behavioral inventories: The Perceived Stress Scale, Healthy Lifestyle questionnaire (HLPCQ), Holmes Rahe Life Stress Inventory, NDDI-E depression scale, GAD-7, Beck Anxiety Inventory, and the Adverse Childhood Events (ACE). We will ascertain sleep metrics through the use of the Õura ring. Please find the schedule of these labs and assessments in Appendix IV Assessment Schedule. For more information about what each assessment provides, please refer top Appendix IX. The EEG, metabolic testing and behavioral inventories will serve to correlate objective and subjective findings.

HYPOTHESES:

• PBM, when applied 3 times weekly over a 15-20-week period (45 sessions), will reduce behavioral symptoms of the stress accompanying epilepsy by at least 20% as shown based upon psychological inventories (see Appendix I).
• PMB, when applied 3 times weekly over a 15-20-week period (45 sessions), will positively affect brain connectivity metrics (bring z-score values closer to the mean based upon a neurotypical database comparison [Appendix II]), in alpha peak frequency and in specific networks that correlate with h positive outcomes in behavioral symptoms as outlined in Hypothesis 1.
• PBM, when applied 3 times weekly over a 15-20-week period (45 sessions), will tend to normalize lab values as measured by urine, blood, and hair samples throughout the study.

Procedures:

This is a single-blinded, randomized clinical study design, that will strive for 80 participants who have been medically-diagnosed with epilepsy and will perform a statistical power analysis at 40 participants to determine the most efficient n to accomplish meaningful outcomes. Kerson will provide informed consent and IRB approval through the Saybrook University IRB. The four sites (Cincinnati, Stephanie Ryall; Houston, Ron Swatzyna; Miami, Natasha Nesic; Warren, OH, Holly Maggiano) will recruit participants from the sites listed in Appendix III (more sites are being considered) and randomized using blinded randomization methodology to a 2:1 grouping (active, control respectively). The Vielight Pro 2 (Vielight Neurotechnology, Toronto, Canada) device will provide the PBM active and control interventions.

At the Intake Meeting (T0), once time is allowed for informed consent discussion and is signed, intake assessments will occur. The participant will go to an outside lab to complete preliminary lab samples. Once all inclusion criteria are met, the baseline (T1) measures will be taken, and another lab visit will take place. Mid-session assessment and more lab work will occur between PBM sessions 21 and 22 (T2). One week after completion of the intervention post-assessments and lab work will be administered (T3). Sessions will be numbered S1-S45. Follow-up assessments and lab work will occur at 6 months post-intervention (T4).

This study will utilize TherapyNotes at www.therapynotes.com (TherapyNotes, Horsham, PA, USA), a HIPAA-compliant online software for participant reports and internal communications. As well, a script-like protocol will be adhered to at each of the four sites to provide confidence that all sites are regulated in style and clinical atmosphere to maintain fidelity. The study fidelity monitor (Kerson) will periodically join sessions via Zoom to confirm and support uniformity at all sites with all researchers, technicians and others who will be in contact with the participants.

Inclusion Criteria:

• • >18 YO

  • Epilepsy - medical diagnosis with at least one seizure within the past 6 months: diagnosis to be obtained from medical records from the treating physician by signature of HIPAA-compliant medical release form
  • Agreement to maintain or reduce medication regimen (based upon prescribers' advice)
  • Available for intake, baseline, post-treatment, 6-month follow-up assessments, and 45 sessions of PBM
  • Willingness to wear an Õura ring at all times (except for charging) for the duration of the study.

Exclusion:

• < 17 YO
• Substance use
• Personality disorders
• Heavy metal toxicity
• Mold toxicity
• Metabolic measures thresholded based on participant type
• Increase in current medication (dosage and/or type)
• No new medications prescribed (reduction as prescribed by prescribing physician OK)
• Current brain bleed
• Acute TBI within the last 12 months
• History of neuromodulation, including ECT
• Brain implants/pumps/shunts
• History of brain surgery
• Hormone replacement therapy for menopause or gender transition
• Untreated sleep disorders

Exclusion Criteria:

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