Efficacy and Safety of Photobiomodulation in MELAS: Protocol for a Series of N-of-1 Trials

<b>Background</b>: There is no cure for mitochondrial diseases which manifest in numerous ways including fatigue, muscle weakness, and exercise intolerance. Medical treatment varies and focuses on managing symptoms. Photobiomodulation (PBM) can decrease mitochondrial damage thereby increasing energy production and decreasing cell death. This pilot study will apply PBM to people with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) to examine the safety of application, and if changes occur in symptoms and signs after cross-over application/withdrawal of a sham or active PBM treatment including a two-week period of washout. <b>Methods</b>: This study is an exploratory, prospective series N-of-1 (single patient) studies. The protocol is guided by the CONSORT extension for reporting N-of-1 trials (CENT 2015), chosen due to the rarity of mitochondrial diseases, the fluctuating symptomology, and heterogeneity of the clinical presentation. The primary outcome is patient-reported fatigue assessed using the Checklist of Individual Strength and with concomitant evaluation of safety. Secondary measures are of depression, anxiety and stress, sleepiness, physical activity, blood lactate and creatine kinase, physical measures of sit-to-stand, and heel raise capability. Mitochondrial function will be evaluated using hydrogen magnetic resonance spectroscopy for lactate. PBM will be a participant-administered, home-based therapy using a multiple diode flexible array (BeniLight iLED-Pro Multi-Wave Multi-Pulse belt; 465 nm, 660 nm, 850 nm; average irradiance 5.23 mW/cm²; total joules: 770.1 J/treatment, all sites; 5 KHz; 20% duty ratio) over the anterior thigh muscles, posterior calf muscles and abdomen for 10 min to each site, three times/week. The safety of the intervention will be assessed. Descriptive statistics, causal analyses of time series data and dynamic modelling will be applied as relevant to the variables collected. Hydrogen magnetic resonance spectra will be acquired and averaged to obtain the content of the targeted hydrogen levels. <b>Discussion</b>: The study will provide guidance on whether and how to progress to a larger, randomised cohort study with sham control.