An Open Label, One Arm, Dose Escalation Study to Evaluate The Safety of Extremely Low Frequency Magnetic Fields in Acute Ischemic Stroke

Research Article

Austin J Cerebrovasc Dis & Stroke. 2014;1(1): 1002.

An Open Label, One Arm, Dose Escalation Study to Evaluate The Safety of Extremely Low Frequency Magnetic Fields in Acute Ischemic Stroke

Capone F1,2*, Corbetto M1, Barbato C1, Pellegrino G1, Di Pino G1,2, Assenza G1, Setti S3, Cadossi R3 and Di Lazzaro V1,2

1Department of Neurology, Campus Bio-Medico University of Rome, Italy

2Department of Neurology Fondazione Alberto Sordi - Research Institute for Ageing, Italy

3Department of Biomedical Sciences, IGEA Biophysics Laboratory, Italy

*Corresponding author: Capone F, Department of Neurology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.

Received: May 25, 2014; Accepted: June 16, 2014; Published: June 18, 2014

Abstract

There is great interest on the development of novel therapies for acute ischemic stroke, because, to date, thrombolysis is the only approved treatment. Recent evidence suggests that Extremely Low Frequency Magnetic Fields (ELF-MF) could represent an alternative approach for acute ischemic stroke therapy, because of their effects on the main mechanisms of brain ischemic damage and regeneration. Main purpose of this open label, one arm, dose escalation study is the validation of ELF-MF stimulation as non-invasive and safe tool to promote recovery in acute ischemic stroke patients. Nine patients will be treated daily for 5 consecutive days, starting within 48 hours from the onset of stroke. Three dose cohorts of three patients each, will be stimulated with pulsed ELF-MF (75 Hz, 1,8 mT) at duration-increasing daily exposure (45, 120, 240 min). The primary outcome (safety endpoint) will be evaluated by the incidence of adverse events and mortality throughout the stimulation period and after 1-year follow-up. Change from baseline of clinical and radiological scores will be taken as secondary outcomes. This study aims at establishing the safety and tolerability of the ELF-MF stimulation in acute ischemic stroke.

Keywords: Stroke; Brain Ischemia; Extremely low frequency Magnetic fields; Pulsed magnetic fields; ELF; Neuroprotection

Abbreviations

ELF-MF: Extremely Low Frequency Magnetic Fields; MRI: Magnetic Resonance Imaging; NIHSS: National Institutes of Health Stroke Scale; AEs: Adverse Events; SAEs: Severe AEs; CTCAE: Common Terminology Criteria for Adverse Events; mRS: Modified Rankin Scale; BI: Barthel Index; FLAIR: Fluid-Attenuated Inversion Recovery; DWI: Diffusion-Weighted Imaging; ADC: Apparent Diffusion Coefficient; ILV: Ischemic Lesion Volume; TMG: Trial Management Group; PI: Principal Investigator

Introduction

Thrombolysis is the only approved treatment for acute ischemic stroke and so, there is great interest in the development of alternative therapies. Despise, for the last two decades, several neuroprotective drugs have been investigated with clinical trials, none of them proved to be efficacious. Recent evidence suggests that the application of Extremely Low Frequency Magnetic Fields (ELF-MF) could be an alternative approach, because of their effects on the main mechanisms underlying brain ischemic damage and regeneration. Indeed, in-vitro studies have shown that ELF-MF modify genes expression, promote neurite outgrowth [1], reduce apoptosis [2], facilitate neuronal differentiation of stem cells [3] and increase BDNF production [4]. In particular, ELF-MF delivered in pulsed mode can selectively modulate glutamate [5] and adenosine [6] receptors. The neuroprotective potential of pulsed ELF-MF has been also confirmed in animal models of brain ischemia. Grant et al. have evaluated the effects of pulsed ELF-MF on cerebral damage in a rabbit model of transient focal ischemia. They found that pulsed ELF-MF exposure, immediately after the onset of ischemia, attenuated cortical edema on Magnetic Resonance Imaging (MRI) and reduced neuronal damage on histological examination [7]. These results have been recently confirmed in mice by Pena-Philippides et al. who evaluated the effect of pulsed ELF-MF on ischemic infarct size and post stroke inflammation [8]. They found that pulsed ELF-MF reduced the infarct size and changed the profile of inflammatory cytokines, thus unveiling anti-inflammatory and anti-apoptotic effects. Recent evidence suggests that ELF-MF might influence human brain function. These findings are supported by the results of the neurophysiological studies that revealed measurable changes in brain electrical activity following ELF-MF exposure [9]. In particular, Capone et al. demonstrated that pulsed ELF-MF can influence cortical excitability and do not produce side effects in healthy volunteers [10]. Purpose of this study is the validation of pulsed ELF-MF stimulation as non-invasive, safe and effective tool to promote recovery in acute ischemic stroke patients.

Materials and Methods

Design

This is an open label, one arm, and dose escalation exploratory study aiming to evaluate the safety of pulsed ELF-MF stimulation in acute ischemic stroke. Subject’s part of the control group will be selected from patients admitted to our clinic for acute ischemic stroke during the last year. The trial consists of a 5-days intervention treatment phase and of a 12-months follow-up phase (Figure1).

Citation: Capone F, Corbetto M, Barbato C, Pellegrino G , Di Pino G, et al. An Open Label, One Arm, Dose Escalation Study to Evaluate The Safety of Extremely Low Frequency Magnetic Fields in Acute Ischemic Stroke. Austin J Cerebrovasc Dis & Stroke. 2014;1(1): 1002. ISSN: 2381-9103.