Neuroprotection in Acute Cerebral Ischemia II

Official title

Multicenter, Prospective, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Effect of I-NIC Therapy in Patients With Acute Ischemic Stroke.

Overview

The goal of this clinical trial is to evaluate whether low-frequency, low-intensity transcranial magnetic stimulation (ELF-MF), delivered by the I-NIC medical device, is effective and safe in treating patients with acute ischemic stroke. The study aims to answer the following questions: Does ELF-MF stimulation with the I-NIC device improve outcomes in patients with acute cerebral ischemia? Is the treatment safe and well tolerated? Researchers will compare the I-NIC device to a placebo device (identical in appearance but without active stimulation), both in addition to standard care, to determine its effectiveness. Participants will: * Be randomly assigned to receive either standard care plus I-NIC treatment or standard care plus a placebo device * Start treatment within 48 hours of symptom onset * Receive daily treatment sessions of 120 minutes for 5 consecutive days * Undergo clinical and neurological evaluations at baseline, 7 days, and 90 days (the 90-day visit may be conducted remotely) * Provide clinical and demographic data during the study This is a phase 3, multicenter, randomized, double-blind, placebo-controlled study involving 364 patients across 14 centers in Italy, with a total study duration of 3 months per participant.

Interventions

• Device Treatment with the I-NIC medical device for neuroprotection
  Treatment with low-frequency, low-intensity transcranial magnetic stimulation (ELF-MF) administered using the I-NIC medical device.
• Device Treatment with I-NIC sham device
  The sham I-NIC device will be connected to a sham solenoid identical to the active solenoid but not emitting any electromagnetic field

Primary outcome measures

• Modified Rankin Scale (mRS) [Time frame: 90 days]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Diagnosis of ischemic stroke in the middle cerebral artery territory, confirmed by clinical evaluation by a neurologist. Baseline CT scan and follow-up CT/MRI at 12-36 hours are required
• Patients with a diagnosis of acute ischemic stroke, with symptom onset within 48 hours prior to clinical evaluation. In cases of unwitnessed onset, the time of onset is defined as the last time the patient was seen well ("last seen well")
• NIHSS score ≥ 6 at randomization (after any reperfusion treatment, if applicable)
• Written informed consent signed by the patient or legal representative.

Exclusion criteria

• Previous ischemic or hemorrhagic stroke with residual mRS > 1
• Pre-stroke modified Rankin Scale (mRS) > 1
• Other severe or complex conditions that may confound the evaluation of the treatment
• Pregnant or breastfeeding women, or women with a positive or indeterminate pregnancy test; women of childbearing potential who cannot exclude the possibility of pregnancy
• Diagnosis of lacunar syndrome
• History of epilepsy or occurrence of seizures in the acute post-stroke phase
• Ongoing treatment with anti-glutamatergic drugs: memantine, ketamine, and lamotrigine
• Undergoing decompressive craniectomy
• Current participation in other interventional clinical studies
• Presence of symptomatic intracranial hemorrhage. For asymptomatic hemorrhagic transformations, the SITS-MOST classification will be used:

HI 1: small petechiae along the margins of the infarct HI 2: more confluent petechiae within the infarct area without space-occupying effect PH 1: blood clot(s) not exceeding 30% of the infarct area with mild space-occupying effect PH 2: blood clots exceeding 30% of the infarct area with significant space-occupying effect PHr 1: small or medium-sized blood clots located remote from the infarct, possibly with mild space-occupying effect PHr 2: large confluent dense blood clots remote from the infarct, with significant space-occupying effect.

Only patients classified as HI1 and HI2 may be enrolled, at the investigator's discretion. Patients classified as PH1, PH2, PHr1, or PHr2 will be excluded from the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Psychogios M, Brehm A, Ribo M, Rizzo F, Strbian D, Raty S, Arenillas JF, Martinez-Galdamez M, Hajdu SD, Michel P, Gralla J, Piechowiak EI, Kaiser DPO, Puetz V, Van den Bergh F, De Raedt S, Bellante F, Dusart A, Hellstern V, Khanafer A, Parrilla G, Morales A, Kirschke JS, Wunderlich S, Fiehler J, Thomalla G, Lemmens R, Peluso JP, Bolognese M, von Hessling A, van Es A, Kruyt ND, Coutinho JM, Castano PMID 39908430
• Capone F, Liberti M, Apollonio F, Camera F, Setti S, Cadossi R, Quattrocchi CC, Di Lazzaro V. An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke. Sci Rep. 2017 Sep 22;7(1):12145. doi: 10.1038/s41598-017-12371-x. PMID 28939890
• Capone F, Dileone M, Profice P, Pilato F, Musumeci G, Minicuci G, Ranieri F, Cadossi R, Setti S, Tonali PA, Di Lazzaro V. Does exposure to extremely low frequency magnetic fields produce functional changes in human brain? J Neural Transm (Vienna). 2009 Mar;116(3):257-65. doi: 10.1007/s00702-009-0184-2. Epub 2009 Feb 3. PMID 19189041
• Grant G, Cadossi R, Steinberg G. Protection against focal cerebral ischemia following exposure to a pulsed electromagnetic field. Bioelectromagnetics. 1994;15(3):205-16. doi: 10.1002/bem.2250150305. PMID 8074737
• Capone F, Salati S, Vincenzi F, Liberti M, Aicardi G, Apollonio F, Varani K, Cadossi R, Di Lazzaro V. Pulsed Electromagnetic Fields: A Novel Attractive Therapeutic Opportunity for Neuroprotection After Acute Cerebral Ischemia. Neuromodulation. 2022 Dec;25(8):1240-1247. doi: 10.1111/ner.13489. Epub 2022 Feb 2. PMID 34480781
• Varani K, Gessi S, Merighi S, Iannotta V, Cattabriga E, Spisani S, Cadossi R, Borea PA. Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils. Br J Pharmacol. 2002 May;136(1):57-66. doi: 10.1038/sj.bjp.0704695. PMID 11976268
• Capone F, Zini A, Valzania F, Diomedi M, Tugnoli V, Leocani L, Comi G, Anzalone N, Contardi S, Colella M, Liberti M, Salati S, Setti S, Cadossi R, Di Lazzaro V. Neuroprotective Effects of Pulsed Electromagnetic Fields in Acute Stroke. J Stroke. 2024 Sep;26(3):458-462. doi: 10.5853/jos.2024.01529. Epub 2024 Sep 27. No abstract available. PMID 39326864

Identifiers

NCT: NCT07552818 · I-NIC 2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗