Weak scalp electrical stimulation to protect the brain after an acute ischemic stroke

Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial 2

This trial will test whether a weak electrical current applied to the scalp can increase collateral blood flow and protect brain tissue in adults with acute ischemic stroke who are not candidates for clot removal.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, Los Angeles (other)
• Locations: 3 sites (Los Angeles, California and 2 other locations)
• Trial ID: NCT06440707 on ClinicalTrials.gov

What this trial studies

This is a multi-site, phase 2a, randomized, sham-controlled, adaptive study testing cathodal high-definition transcranial direct current stimulation (C-tDCS) in acute ischemic stroke. Eligible patients who arrive at participating emergency departments within 24 hours of last known well and who are not candidates for endovascular thrombectomy will be enrolled and stratified by thrombolytic eligibility. Participants are randomized 5:1 to active stimulation versus sham, and active-arm patients receive varying doses (strength and duration) in ranked cohorts to identify an optimal dose. The primary outcomes focus on safety and imaging markers of tissue salvage and collateral blood flow measured with multimodal brain scans.

Who should consider this trial

Good fit: Adults (over 18) with an acute focal neurologic deficit from ischemic stroke, NIHSS score ≥4 (or disabling deficit if NIHSS <4), cortical vessel occlusion, and a salvageable penumbra on imaging who can be treated within 24 hours are ideal candidates.

Not a fit: Patients who are eligible for endovascular thrombectomy, lack a salvageable penumbra on imaging, present after 24 hours, or have non-cortical strokes are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could increase blood flow to threatened brain tissue and improve outcomes for patients who cannot receive clot-removal therapies.

How similar studies have performed: Noninvasive brain stimulation has shown mixed, mostly preliminary results for stroke recovery, and using cathodal tDCS specifically for acute neuroprotection and collateral enhancement is largely novel and unproven.

Eligibility criteria

Inclusion Criteria:

* New focal neurologic deficit consistent with AIS
* National Institute of Health Stroke Scale (NIHSS) ≥4 or NIHSS\< 4 in the presence of disabling deficit (a deficit that, if unchanged, would prevent the
* patient from performing basic activities of daily living such as bathing, ambulating, toileting, hygiene, and eating or returning to work)
* Age\>18
* Presence of any cortical vessel occlusion, including Internal Carotid Artery, branches of Middle Cerebral Artery, Anterior Cerebral Artery, Posterior Cerebral Artery, Posterior-Inferior Cerebellar Artery
* Presence of salvageable penumbra with perfusion lesion volume to ischemic core volume ratio of ≥ 1.2 on multimodal imaging
* Patient ineligible for endovascular thrombectomy per American Heart/Stroke Associations Guidelines
* Patient is able to be treated with tDCS within 24 hours of last known well time
* A signed informed consent is obtained from the patient or patient's legally authorized representative

Additional inclusion criteria for non-thrombolytic patients

• Patient ineligible for IV lytics per American Heart/American Stroke Associations National Guidelines

Additional inclusion criteria for thrombolytic receiving patients

* Patient eligible for tPA per Guidelines
* Within 2-hours from intravenous thrombolytic start of administration

Exclusion Criteria:

* Acute intracranial hemorrhage
* Presence of MRI and gadolinium contraindications including cardiac implantable devices, cochlear implant, implanted neurostimulation device, unremovable metallic body piercing, magnetic dental implants, drug infusion pumps, estimated glomerular filtration rate of less than 35 mL/min/1.73 m2, allergy to gadolinium
* Evidence of a large Ischemic core volume more than equal to 100 cc
* Presence of transcranial direct current stimulation contraindications - electrically or magnetically activated intracranial metal and non-metal implants.
* Pregnancy
* Signs or symptoms of acute myocardial infarction on admission
* History of seizure disorder or new seizures with presentation of current stroke
* 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
* Concomitant experimental therapy
* Preexisting scalp lesion at the site of the stimulation or presence of skull defects (may alter current flow
* pattern)
* Preexisting coagulopathy
* Patients suspected of having infective endocarditis and ischemic stroke related to septic emboli
* Patients suspected or known to be infected with coronavirus 2019 (COVID-19)
* Patient with radiographic evidence or suspicion of chronic conditions that may predispose them to intracranial hemorrhage, including brain arteriovenous malformations, cerebral cavernous malformations, cerebral telangiectasia, multiple previous intracerebral hemorrhages (amyloid angiopathy)
* Suspected cerebral vasculitis based on medical history and imaging
* Suspected cysticercosis
* Suspected cranial dural arteriovenous fistula
* Cerebral venous thrombosis
* Head trauma causing loss of consciousness, concussion, confusion, or a headache within the past 30 days
* Patient has suffered a hemorrhagic or ischemic stroke within the last three (3) months
* History of cancer known to cause hemorrhagic metastases, e.g., melanoma, renal cell carcinoma,
* choriocarcinoma, thyroid carcinoma, lung carcinoma, breast carcinoma, and hepatocellular carcinoma
* History of left atrial myxoma
* Evidence of dissection in the intracranial cerebral arteries
* Suspicion of aortic dissection
* Significant mass effect with midline shift
* The patient is in a coma

Where this trial is running

Los Angeles, California and 2 other locations

• University of California- Los Angeles (UCLA) — Los Angeles, California, United States (RECRUITING)
• Johns Hopkins Medical Center — Baltimore, Maryland, United States (RECRUITING)
• Duke Medical Center Hospital — Durham, North Carolina, United States (RECRUITING)

Study contacts

• Study coordinator: Mersedeh Bahr-Hosseini, MD

Conditions: Acute Ischemic Stroke, Cytoprotection, Collateral enhancement