Transcranial Direct Current Stimulation for Treatment of Acute Ischemic Stroke

NCT ID: NCT06440707

Last Updated: 2025-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-15

Study Completion Date

2030-08-01

Brief Summary

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Many patients with acute ischemic stroke are ineligible for currently available standard treatments (clot-busting medication, also known as intravenous thrombolytic or mechanical removal of a clot), and many are non-responders, resulting in a low rate of excellent outcomes, which necessitates the development of novel therapies.

In this study, investigators are testing a new treatment in which a weak electrical current will be applied via scalp electrodes to increase collateral blood flow to the brain and rescue the brain tissue at risk of injury. The primary aim is to find an optimal dose of this therapy that is both adequately safe and effective on imaging markers of brain tissue rescue.

Detailed Description

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This multi-site, phase 2a, randomized, sham-controlled, adaptive study aims to identify an optimal dose of a new treatment, cathodal direct current stimulation or C-tDCS, for acute ischemic stroke. This new treatment involves applying a weak inhibitory electrical current to the brain via scalp electrodes in acute stroke patients. The weak electrical current will electrically protect the brain cells not receiving enough oxygen and nutrients due to blood vessel blockage and increase the collateral blood flow to the brain.

The study primarily aims to find an optimal dose that shows adequate safety and effectiveness on markers of brain protection and collateral blood flow enhancement using brain scan. The investigators will ask acute stroke patients who arrive at the Emergency Departments of the University of California Los Angeles (UCLA), Duke, and Johns Hopkins Medical Center and are not candidates for clot removal procedure (endovascular thrombectomy) to participate in the study. The study enrolls patients in 2 subgroups depending on their eligibility for clot-busting medication, also known as thrombolytics (thrombolytic receiving and thrombolytic ineligible groups). Then, patients will be randomized in a 5 to 1 ratio to receive active stimulation versus sham (control with no stimulation).

Amongst patients randomized to the active arm, different doses of electrical current will be tested in various ranks, increasing the strength and the total duration of the electrical current at higher ranks. Computer simulation techniques (Bayesian method) will decide which dose patients should be assigned. The deciding rules of whether to escalate versus de-escalate versus stay on the same dose rank will be the probabilities of brain bleeding of ≤40% and substantial rescue of brain tissue at risk of permanent injury of ≥70%. The functional features and rules of the mathematical technique (Bayesian) will justify enrolling up to 50 patients in each subgroup of lytic-receiving and non-lytic-receiving patients (a total of up to 100 patients in active groups). Additionally, 10 sham (control) patients will be enrolled in each subgroup (a total of up to 20 patients in sham groups).

At 24-30 hours after the study stimulation, patients will receive a brain MRI to assess the presence of any brain bleed and how much brain tissue is rescued (primary aims), as well as to examine the additional effects of the study stimulation on brain collateral blood flow and the growth of the permanently damaged brain tissue.

As part of the study's additional goals, the treatment's tolerability will be studied by asking patients about how they feel during and after each session. Patients will also be neurologically examined after each session. Four days after enrollment, a brief neurological assessment will be performed if the patient is still in the hospital. On day 30, patients will receive a call from research personnel to see how they are doing. On day 90, they will be asked to come to neurology clinic to be neurologically assessed. The information gathered from this study will be used to advance this new treatment to future larger studies.

Conditions

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Acute Ischemic Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Adaptive Bayesian Design
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Transcranial Direct Current Stimulation in patients ineligible for intravenous thrombolytic

Patients in the active stimulation group receive cathodal transcranial electrical stimulation via 5 small electrodes for 20 to 60 minutes (min) at 1 or 2 milliamperes (mA) intensities. The duration and intensity of the stimulation will determined by the dose Tier the patient is assigned to. There will be 5 dose tiers, reflecting increasing intensity and duration of stimulation: Tier1- 2 mA, single 20 min cycle; Tier 2 - 1 mA, 2 cycles of 20 min/20 min off; Tier 3- 2mA, 2 cycles of 20 min/20 min off; Tier 4 - 1 mA, 3 cycles of 20min/20 min off; Tier 5 - 2 mA, 3 cycles of 20 min/20 min off.

The decision to which dose Tier the patient should be assigned will be determined by the mathematical Bayesian model.

Group Type ACTIVE_COMPARATOR

High-definition Cathodal Transcranial Direct Current Stimulation (HD C-tDCS)

Intervention Type DEVICE

The active study treatment involves delivering a weak form of electrical stimulation via 5 small electrodes to the brain tissue at risk of infarction.

Sham stimulation in patients ineligible for intravenous thrombolytic

Patients in the sham stimulation arm will have the cap and electrodes in place but will not receive electrical stimulation.

Group Type SHAM_COMPARATOR

Sham tDCS

Intervention Type DEVICE

Sham patients will have cap and electrodes in place, but no stimulation will be delivered.

Transcranial Direct Current Stimulation in patients receiving intravenous thrombolytic

Patients in the active stimulation group receive cathodal transcranial electrical stimulation via 5 small electrodes for 20 to 60 minutes (min) at 1 or 2 milliamperes (mA) intensities. The duration and intensity of the stimulation will determined by the dose Tier the patient is assigned to. There will be 5 dose tiers, reflecting increasing intensity and duration of stimulation: Tier1- 2 mA, single 20 min cycle; Tier 2 - 1 mA, 2 cycles of 20 min/20 min off; Tier 3- 2mA, 2 cycles of 20 min/20 min off; Tier 4 - 1 mA, 3 cycles of 20min/20 min off; Tier 5 - 2 mA, 3 cycles of 20 min/20 min off.

The decision to which dose Tier the patient should be assigned will be determined by the mathematical Bayesian model.

Group Type ACTIVE_COMPARATOR

High-definition Cathodal Transcranial Direct Current Stimulation (HD C-tDCS)

Intervention Type DEVICE

The active study treatment involves delivering a weak form of electrical stimulation via 5 small electrodes to the brain tissue at risk of infarction.

Sham stimulation in patients receiving intravenous thrombolytic

Patients in the sham stimulation arm will have the cap and electrodes in place but will not receive electrical stimulation.

Group Type SHAM_COMPARATOR

Sham tDCS

Intervention Type DEVICE

Sham patients will have cap and electrodes in place, but no stimulation will be delivered.

Interventions

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High-definition Cathodal Transcranial Direct Current Stimulation (HD C-tDCS)

The active study treatment involves delivering a weak form of electrical stimulation via 5 small electrodes to the brain tissue at risk of infarction.

Intervention Type DEVICE

Sham tDCS

Sham patients will have cap and electrodes in place, but no stimulation will be delivered.

Intervention Type DEVICE

Eligibility Criteria

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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


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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role lead

Responsible Party

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Mersedeh Bahr Hosseini, MD

Associate Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of California- Los Angeles (UCLA)

Los Angeles, California, United States

Site Status RECRUITING

Johns Hopkins Medical Center

Baltimore, Maryland, United States

Site Status RECRUITING

Duke Medical Center Hospital

Durham, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Mersedeh Bahr-Hosseini, MD

Role: CONTACT

310-794-1195

Jeffrey Saver, MD

Role: CONTACT

310-794-1195

Facility Contacts

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Mersedeh Bahr Hosseini, MD

Role: primary

310-794-6379

Jeffrey L Saver, MD

Role: backup

310-794-6379

Argye E Hillis, MD

Role: primary

(443) 287-4610

Melissa Stockbridge, PhD

Role: backup

Wayne Feng, MD

Role: primary

919-660-4195

Salman Ikramuddin, MD

Role: backup

919-255-0870

Other Identifiers

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24-000780

Identifier Type: -

Identifier Source: org_study_id

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