Journal Article

TRANscranial direct current stimulation for FOcal Refractory epilepsy in mitochondrial disease (TRANSFORM): delayed-start, randomised, double-blinded, placebo-controlled study

Ng, Yi Shiau, Baker, Mark, Gorman, Grainne, Bangel, Katrin A., Winder, Amy, McFarland, Robert, Lim, Albert Z., Bulmer, Joseph, Blain, Alasdair

2024

Overview

Background Focal epilepsy is common in children and adults with mitochondrial disease. Seizures are often refractory to pharmacological treatment and, in this patient group, frequently evolve to refractory focal status epilepticus (also known as epilepsia partialis continua ). Where this occurs, the long-term prognosis is poor. Transcranial DC stimulation (tDCS) is a promising, non-invasive, adjunctive treatment alternative to common surgical procedures. Limited recruitment of study participants with this rare disease and the ethical challenges of administering a treatment to one group and not another, while maintaining strict methodological rigour can pose challenges to the design of a clinical study. Method We designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy. We will include participants with a genetically confirmed diagnosis of mitochondrial disease with drug-resistant focal epilepsy aged ≥ 2 years, aiming to collect 30 episodes of focal status epilepticus , each treated for a maximum period of 14 days. The early start intervention arm will receive tDCS from day 1. The delayed start intervention arm will receive sham stimulation until crossover on day 3. Our primary endpoint is a greater than 50% reduction from baseline (on day 0) in seizure frequency assessed by 3x daily reporting, accelerometery, and video monitoring. Changes in the underlying epileptogenic focus within the brain related to the tDCS intervention will be assessed by magnetic resonance imaging (MRI) and/or electroencephalography (EEG). Discussion Study results in favour of treatment efficacy would support development of tDCS into a mainstream treatment option for focal epileptic seizures related to mitochondrial disease. Trials registration ISRCTN: 18,241,112; registered on 16/11/2021.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adolescent / Adult / Adults / Brain research / Care and treatment / Caregivers / Child / Clinical trials / Complications and side effects / Convulsions & seizures / Delayed-start study design / Diagnosis / Double-Blind Method / Drug resistance / Drug Resistant Epilepsy - therapy / Drug therapy / EEG / Electrical stimulation of the brain / Electroencephalography / Epilepsies, Partial - therapy / Epilepsy / ESB / Female / Guardians / Hospitals / Humans / Informed consent / Intensive care / Magnetic brain stimulation / Magnetic resonance imaging / Male / Medicine / Medicine & Public Health / Middle Aged / Mitochondria / Mitochondrial disease / Mitochondrial diseases / Mitochondrial Diseases - complications / Mitochondrial Diseases - therapy / Mitochondrial epilepsy / Neurochemistry / Neurodegeneration / Neuroimaging / Neurology / Neurosurgery / Participation / Patient outcomes / Patients / Pediatrics / Pharmacoresistant epilepsy / Refractory focal seizures / Seizures / Study Protocol / Transcranial direct current stimulation (tDCS) / Transcranial Direct Current Stimulation - methods / Treatment Outcome / Young Adult