An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Abstract

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach.

Patient Semi-specific Computational Modeling of Electromagnetic Stimulation Applied to Neuroprotective Treatments in Acute Ischemic Stroke

“…As shown in Capone et al 17 , this source application implied a gradient of B transverse to the head that decreases with the distance from the solenoid itself. From a dosimetric point of view, this opened the question on the exposure experimented by the different ischemic regions as a function of distance.…”

“…The study was registered with ClinicalTrials.gov, number NCT01941147 (September 9, 2013). The study protocol has been published 40 . Numerical dosimetry was performed on the three subjects exposed for 120 minutes.…”

“…Specifically, in the context of ongoing studies intended to demonstrate whether PEMFs are able to elicit a neuroprotective effect on patients with ischemic stroke, the objective of the present paper was to identify a methodology for a dose-response curve assessment suitable to be applied in a large scale clinical study. To this scope, we analysed in details the exposure undergone in the study of Capone et al 17 . In particular, we aimed to demonstrate that the type of exposure obtained with a single solenoid placed laterally to the head and co-centered with the ischemic lesion is able to induce a magnetic pulse with peak values above 1 mT under proper conditions.…”

“…This is necessary if one, aiming to introduce a new electromagnetic-based therapy, like the I-NIC, wants to follow an approach similar to the drugs clinical trials, as an example one can think to a typical Phase2 study 39 . Limitations: This methodology was conceived for the ongoing I-NIC study 18 , but here it is applied to the reduced sample of the three patients recruited in Capone et al 17 that underwent magnetic stimulation for 120 minutes (the same treatment duration as the one used in the I-NIC study 18 ). Thus, such an approach will be a powerful tool to a reliable assessment of a dose-response threshold of the treatment when a large number of patients will be evaluated.…”

“…Such a methodology is applied here to the reduced sample of the three patients recruited in Capone et al 17 that underwent magnetic stimulation for 120 minutes (the same treatment duration as the one used in the I-NIC study 18 ). Such a pool of data seems to be consistent with the final aim since in both cases, the magnetic source is a single monolateral solenoid placed on the patient head, therefore the dosimetric methodology proposed here will be applicable for the I-NIC study 18 .…”