Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke Before and After Thrombectomy (TESSERACT-BA)

Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial_ Bridging and Adjunctive Neuroprotection

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 before and after endovascular therapy.

Study Overview

• Status: Terminated
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation (tDCS)

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 undergoing recanalization procedure. 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. All patients will be receiving the first dose (stimulation cycle) after the recanalization procedure and patients at dose tiers 5-6 will also be receiving stimulation cycles before the recanalization procedure begins.

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

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California- Los Angeles (UCLA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• New focal neurologic deficit consistent with AIS
• Age≥18
• NIHSS ≥ 4
• ICA or M1 or M2 MCA occlusion on pre-thrombectomy MRA or CTA
• Onset (last-seen-well) time to randomization time within 24 hours
• Pre-stroke modified Rankin Scale≤ 3.
• Patient ineligible for IV tPA, per national AHA/ASA Guidelines.
• Having undergone endovascular thrombectomy with less than a complete reperfusion (<TICI 2c, 3) for receiving post-thrombectomy adjunct C-tDCS.
• Undergoing endovascular thrombectomy, per national AHA/ASA Guidelines for patients who are assigned to pre-thrombectomy bridging session at Tiers 5, 6.
• A signed informed consent is obtained from the patient or patient's legally authorized representative

Exclusion criteria

• Acute intracranial hemorrhage
• Evidence of a large Ischemic core volume (ADC < 620 µm2/s or rCBF< 30%) ≥ 100 ml
• Presence of tDCS contraindications - electrically or magnetically activated intracranial metal and non-metal implants.
• Pregnancy
• Severe contrast allergy or absolute contraindication to iodinated contrast preventing endovascular intervention.
• 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, consist of a platelet count of ≤ 100, INR ≥ 3, PTT ≥ 90.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation arm; Patients will be randomized to active treatment (C-tDCS) vs sham stimulation in a 3:1 ratio. There will be 6 dose tiers: Tier 1 - 1 mA, and Tier 2- 2 mA: Consist of a single stimulation cycle (20min) after the endovascular procedure (EVT) in patients with TICI<2c,3 and negative immediate post-EVT CT scan for definitive evidence of ICH. Tier 3 - 1 mA and Tier 4- 2mA consist of 2 treatment cycles after the EVT in patients with TICI<2c and 3, and negative immediate post-EVT CT scan for definitive evidence of ICH. Tier 5 - 1 mA and tier 6- 2 mA consist of 3 treatment cycles. The first cycle will be up to 20 min cycle, after initial imaging and prior to arterial puncture, the second and third cycles after EVT in patients with TICI<2c and 3 and negative immediate post-EVT CT scan for definitive evidence of ICH.	Device: Transcranial Direct Current Stimulation (tDCS); 20 minutes of Cathodal tDCS after +/- before endovascular thrombectomy (EVT)
Sham Comparator: Sham arm; Patients in the sham stimulation arm at all the tiers will have the cap and electrodes in place, and sham switch moved but without delivery of electrical stimulation.	Device: Transcranial Direct Current Stimulation (tDCS); 20 minutes of Cathodal tDCS after +/- before endovascular thrombectomy (EVT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Outcome- Number of Participants With Symptomatic Intracranial Hemorrhage (SICH)	Symptomatic intracranial hemorrhage (SICH) is defined as an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) total score within 24 hours of stimulation associated with parenchymal hematoma type 1 (PH1), parenchymal hematoma type 2 (PH2), remote intraparenchymal hemorrhage (RIH), subarachnoid hemorrhage (SAH), or intraventricular hemorrhage (IVH). The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is.	At 24-hour post-stimulation
Primary Tolerability Outcome-Number of Participants Completing the Protocol-assigned Stimulation	The percentage of the patients completing the protocol-assigned stimulation treatment with no intolerability.	After 5 minutes of stimulation period
Primary Feasibility Outcome- Assessing the Speed of Stimulation Implementation From Randomization.	The median times from randomization to bridging C-tDCS initiation and the time form end of endovascular thrombectomy procedure to adjunctive C-tDCS initiation in the last 10 enrolled patients.	Median time from randomization to tDCS initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Safety Outcome-Number of Participants With Asymptomatic Intracranial Hemorrhage (AICH)	AICH is defined as intracranial hemorrhage not associated with National Institute of Health Stroke Scale (NIHSS) total score worsening of ≥ 4. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is.	At 24-hour post-stimulation
Secondary Safety Outcome-Number of Participants With Early Neurologic Deterioration	Worsening of total score ≥ 4 on NIHSS during the 24-hour period after stimulation, with or without intracranial hemorrhage. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Accordingly, 0 is the lowest and 42 is the highest total score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is.	At 24-hour post-stimulation
Secondary Safety Outcome-Number of Participants With Mortality	Rate of mortality	At 90 days post-stimulation
Secondary Safety Outcome-Number of Participants With All Serious Adverse Events (Anticipated and Unanticipated)	A serious adverse event (SAE) is any adverse event that is fatal, is life-threatening, is permanently or substantially disabling, requires or prolongs hospitalization, or requires medical or surgical intervention to prevent one of the above outcomes. Anticipated serious adverse events were defined as SAEs that are expected and related to acute ischemic stroke complications such as headache, stroke recurrence, pneumonia, systemic blood clots, Family withdrawal of care, etc. An unanticipated serious adverse event is an SAE that is not deemed an ischemic stroke complication and adjudicated as possibly related to study treatment.	At 90 days post-stimulation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Imaging Efficacy Outcome- Assessing Imaging Biomarker of Neuroprotection and Collateral Enhancement	By comparing the baseline MR/CT imaging with the MR/CT imaging at 2-hour (early) and 24-hour (final) post-stimulation, the following were planned to be measured: 1) Final penumbra salvage proportion, 2) Final hypoperfusion lesion reduction, 3) Early relative quantitative cerebral blood volume (qrCBV) enhancement.	Change in the penumbral volume between the timepoints: baseline, 2- hour, and 24-hour post-stimulation
Exploratory Clinical Efficacy Outcome- Assessing 3 Months Disability	Examining the clinical outcomes of 3-month modified Rankin Scale. The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.The scale runs from 0-6, running from perfect health without symptoms to death.	At day-90 post stimulation

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: The City College of New York

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2019
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Transcranial direct current stimulation; Bridging neuroprotection; Adjunctive neuroprotection
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: 19-000529

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes