Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke

Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial

This proposal is a prospective, single-center, dose-escalation safety, tolerability, feasibility and potential efficacy study of transcranial direct current stimulation (tDCS) in acute stroke patients with substantial salvageable penumbra due to a large vessel occlusion who are ineligible for intravenous thrombolysis and endovascular therapy.

This is a single center, sham-controlled, dose escalation study where cathodal tDCS is delivered to threatened but not yet irreversibly damaged (penumbral) tissue in patients with large vessel occlusion who are not eligible for blood flow restoring recanalization procedures. Patients will be randomized in a 3:1 design, to cathodal versus sham (control) stimulation, at each six designed dose tiers. The dose tiers will be increasing in both intensity and duration of the stimulation.

The occurrence of symptomatic intracranial hemorrhage will determine the pace of the escalation through the dose tiers.

Inclusion criteria:

1. New focal neurologic deficit consistent with AIS
2. NIHSS≥4 or NIHSS <4 in the presence of disabling deficits
3. Age>18;
4. Presence of any cortical vessel occlusion including ICA, branches of MCA, Anterior Cerebral artery (ACA), Posterior Cerebral artery (PCA), Posterior-Inferior cerebellar artery (PICA);
5. Presence of salvageable penumbra with Tmax> 6 sec/ ischemic core volume (ADC < 620 μm2/s or rCBF< 30%) ≥ 1.2
6. Patient ineligible for IV tPA, per national AHA/ASA Guidelines
7. Patient ineligible for endovascular therapy per AHA/ASA national Guidelines - one or more of: poor prestroke functional status (mRS score >1), mild neurological symptoms (NIHSS <6), large ischemic core (ASPECTS <6), thrombectomy not technically performable due to severe vessel tortuosity, cervical artery chronic occlusion, or other unfavorable angioarchitectural features that preclude endovascular access to the target intracranial vessel. 8) Subject is able to be treated with tDCS within 24 hours of last known well time;

9) A signed informed consent is obtained from the patient or patient's legally authorized representative

Exclusion criteria

1. Acute intracranial hemorrhage
2. Evidence of a large Ischemic core volume (ADC < 620 μm2/s or rCBF< 30%) ≥ 100
3. Presence of tDCS contraindications - electrically or magnetically activated intracranial metal and non-metal implants.
4. Severe MR contrast allergy or renal dysfunction with eGFR<30ml/min, precluding MRI gadolinium or CT iodine contrast
5. Pregnancy
6. Signs or symptoms of acute myocardial infarction, including EKG findings, on admission
7. Suspicion of aortic dissection on admission
8. History of seizure disorder or new seizures with presentation of current stroke
9. Evidence of any other major life-threatening or serious medical condition that would prevent completion of the study protocol including attendance at the 3-month follow-up visit
10. Concomitant experimental therapy
11. Preexisting scalp lesion at the site of the stimulation or presence of skull defects (may alter current flow pattern)
12. Preexisting coagulopathy, consist of platelet count of ≤ 100, INR ≥ 3, PTT ≥ 90.