Clinical trial NCT03574038: Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke
Official title: Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke, Acute
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2018-06-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Traditional 3+3 (rule-based, modified Fibonacci) dose escalation design
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety Outcome: Rate of Symptomatic Intracranial Hemorrhage (SICH) in the Active Treatment Arms Compared to Sham Arm
timeFrame: At 24-hour post-stimulation
measure: Feasibility Outcome: Speed With Which HD C-tDCS Was Implemented
timeFrame: Time from randomization to tDCS initiation assessed up to 30 minutes
measure: Tolerability Outcome: Percentage of the Patients Completing the Protocol-assigned Stimulation Treatment
timeFrame: After 20 minutes of stimulation period
Secondary outcomes:
measure: Secondary Safety Outcome: Rate of Early Neurologic Deterioration in All Active Patients Compared to Sham Arm
timeFrame: During the 24-hour post-stimulation
measure: Secondary Safety Outcome: Rate of Mortality in All Active Patients Compared to Sham Arm,
timeFrame: By day 90 post stimulation
measure: Secondary Safety Outcome: Rate of All Serious Adverse Events Occured During the 90 Days of Study Participation in All Active Patients Compared to Sham.
timeFrame: By day 90 post-stimulation
Other outcomes:
measure: Per-protocol Exploratory Imaging Efficacy Outcome of Imaging Biomarkers of Neuroprotection and Collateral Enhancement Excluding One Patient With no Penumbra at Baseline on Imaging Core Review and One Patient With Septic Embolization as Stroke Cause.
timeFrame: At 2-hour and 24-hour post-stimulation
measure: Per-protocol Exploratory Clinical Efficacy Outcome: Rate of Functional Independence at 3-month in Active vs. Sham Excluding Two Patients, One With no Penumbra Was Present at Baseline on Imaging Core Review and One With Septic Embolization as Stroke Cause.
timeFrame: At day 90 post stimulation
Locations:
city: Los Angeles
country: United States
facility: University of California- Los Angeles (UCLA)
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Mersedeh Bahr Hosseini, MD
role: PRINCIPAL_INVESTIGATOR
References: