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

Primary Purpose

Acute Ischemic Stroke

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Direct Current Stimulation (tDCS)
Sponsored by
University of California, Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring Transcranial direct current stimulation, Bridging neuroprotection, Adjunctive neuroprotection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California- Los Angeles (UCLA)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Stimulation arm

Sham arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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.
Secondary Safety Outcome-Number of Participants With Mortality
Rate of mortality
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.

Full Information

First Posted
July 30, 2019
Last Updated
June 28, 2023
Sponsor
University of California, Los Angeles
Collaborators
The City College of New York
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1. Study Identification

Unique Protocol Identification Number
NCT04061577
Brief Title
Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke Before and After Thrombectomy
Acronym
TESSERACT-BA
Official Title
Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial_ Bridging and Adjunctive Neuroprotection
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Interim Analysis
Study Start Date
July 28, 2019 (Actual)
Primary Completion Date
April 1, 2022 (Actual)
Study Completion Date
April 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles
Collaborators
The City College of New York

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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 before and after 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke
Keywords
Transcranial direct current stimulation, Bridging neuroprotection, Adjunctive neuroprotection

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
Traditional 3+3 (rule-based, modified Fibonacci) dose-escalation design
Masking
Participant
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stimulation arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham arm
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Transcranial Direct Current Stimulation (tDCS)
Intervention Description
20 minutes of Cathodal tDCS after +/- before endovascular thrombectomy (EVT)
Primary Outcome Measure Information:
Title
Primary Safety Outcome- Number of Participants With Symptomatic Intracranial Hemorrhage (SICH)
Description
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.
Time Frame
At 24-hour post-stimulation
Title
Primary Tolerability Outcome-Number of Participants Completing the Protocol-assigned Stimulation
Description
The percentage of the patients completing the protocol-assigned stimulation treatment with no intolerability.
Time Frame
After 5 minutes of stimulation period
Title
Primary Feasibility Outcome- Assessing the Speed of Stimulation Implementation From Randomization.
Description
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.
Time Frame
Median time from randomization to tDCS initiation
Secondary Outcome Measure Information:
Title
Secondary Safety Outcome-Number of Participants With Asymptomatic Intracranial Hemorrhage (AICH)
Description
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.
Time Frame
At 24-hour post-stimulation
Title
Secondary Safety Outcome-Number of Participants With Early Neurologic Deterioration
Description
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.
Time Frame
At 24-hour post-stimulation
Title
Secondary Safety Outcome-Number of Participants With Mortality
Description
Rate of mortality
Time Frame
At 90 days post-stimulation
Title
Secondary Safety Outcome-Number of Participants With All Serious Adverse Events (Anticipated and Unanticipated)
Description
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.
Time Frame
At 90 days post-stimulation
Other Pre-specified Outcome Measures:
Title
Exploratory Imaging Efficacy Outcome- Assessing Imaging Biomarker of Neuroprotection and Collateral Enhancement
Description
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.
Time Frame
Change in the penumbral volume between the timepoints: baseline, 2- hour, and 24-hour post-stimulation
Title
Exploratory Clinical Efficacy Outcome- Assessing 3 Months Disability
Description
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.
Time Frame
At day-90 post stimulation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
University of California- Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke Before and After Thrombectomy

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