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

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ClinicalTrials.gov Identifier: NCT04061577
Recruitment Status : Recruiting
First Posted : August 20, 2019
Last Update Posted : November 9, 2021
Sponsor:
Collaborator:
The City College of New York
Information provided by (Responsible Party):
Mersedeh Bahr Hosseini, MD, University of California, Los Angeles

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.

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Device: Transcranial Direct Current Stimulation (tDCS) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Traditional 3+3 (rule-based, modified Fibonacci) dose-escalation design
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial_ Bridging and Adjunctive Neuroprotection
Actual Study Start Date : July 28, 2019
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : September 1, 2025

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)




Primary Outcome Measures :
  1. Primary safety outcome- rate of symptomatic intracranial hemorrhage (SICH) [ Time Frame: At 24-hour post-stimulation ]

    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.



Secondary Outcome Measures :
  1. Secondary safety outcome-rate of asymptomatic intracranial hemorrhage (AICH) [ Time Frame: At 24-hour post-stimulation ]

    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.


  2. Secondary safety outcome-rate of early neurologic deterioration [ Time Frame: At 24-hour post-stimulation ]

    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.


  3. Secondary safety outcome-rate of mortality [ Time Frame: At 90 days post-stimulation ]
    Rate of mortality

  4. Secondary safety outcome-rate of all serious adverse events [ Time Frame: At 24-hour post-stimulation ]
    A serious adverse event 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


Other Outcome Measures:
  1. Tolerability Outcome- assessing the percentage of the patients completing the protocol-assigned stimulation [ Time Frame: After 20 minutes of stimulation period ]
    The percentage of the patients completing the protocol-assigned stimulation treatment.

  2. Tolerability Outcome- assessing the rate and severity of cutaneous, neurologic, nociceptive adverse events. [ Time Frame: After 20 minutes of stimulation period ]
    The rate and severity of cutaneous, neurologic, nociceptive or other adverse effects will be assessed. First, the rate of occurrence of adverse event will be determined. Then, the severity of adverse event will be graded as mild, moderate and severe and the rate of each will be reported in patients with occurrence of adverse events.

  3. Feasibility Outcome- assessing the speed of stimulation implementation from randomization. [ Time Frame: Median time from randomization to tDCS initiation ≤ 10 minutes ]
    The predefined success threshold for feasibility will be median times from randomization to bridging C-tDCS initiation and the time form end of endovascular thrombectomy procedure to adjunctive C-tDCS initiation ≤ 10 minutes in the last 10 enrolled patients.

  4. Exploratory Imaging Efficacy Outcome- assessing imaging biomarker of penumbral salvage [ Time Frame: Change in the penumbral volume between the timepoints: baseline, 2- hour, and 24-hour post-stimulation ]

    Examining the change in the penumbral ( salvageable brain tissue ) volume from baseline MR/CT perfusion to 2-hr and 24hr post-stimulation MR/CT perfusion.

    The penumbral is the area of brain with delay in arrival of contrast that is not infarcted ( infarct core) yet but is destined to infarction (perfusion lesion minus infarct core).


  5. Exploratory Imaging Efficacy Outcome- assessing imaging biomarker of collateral enhancement [ Time Frame: Between the timepoints: baseline, 2- hour, and 24-hour post-stimulation ]

    Examining the change in the perfusion lesion volume from baseline MR/CT perfusion to 2-hr and 24hr post-stimulation MR/CT perfusion.

    The perfusion lesion is the area of brain with delay in arrival of contrast due to vascular occlusion and contains both the irreversibly damaged brain tissue (infarct core) and salvageable brain tissue (penumbra).


  6. Exploratory Imaging Efficacy Outcome- assessing infarct growth [ Time Frame: Between the timepoints: baseline, 2- hour, and 24-hour post-stimulation ]
    Infarct growth is measured by comparing the volume of irreversibly damaged brain tissue (infarct core) at baseline to 2-hr and 24-hr infarct cores post-stimulation.

  7. Exploratory Clinical Efficacy Outcome- assessing early course improvement in neurological deficits [ Time Frame: Between timepoints: baseline, 2- hour, and 24-hour. ]

    Examining the improvement in National Institute of Health Stroke Scale (NIHSS) Between timepoints: baseline, 2- hour, and 24-hour.

    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.


  8. Exploratory Clinical Efficacy Outcome- assessing 3 months disability [ Time Frame: At day-90 post stimulation ]

    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.


  9. Exploratory Clinical Efficacy Outcome- assessing 3 months quality of life [ Time Frame: At day-90 post stimulation ]

    Examining the clinical outcomes with 3-month EuroQol- 5D.

    EuroQol- 5D is a health-related quality of life scale measuring the quality of life in 5 dimensions: 1- Mobility, 2-self-care, 3- usual activities, 4- pain and discomfort, 5- depression and anxiety. Each dimension grades from 1-5 , running from no issue to having extreme issues/inability to conduct tasks related to each domain.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04061577


Contacts
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Contact: Mersedeh Bahr Hosseini, MD 310-794-6379 mbahrhosseini@mednet.ucla.edu

Locations
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United States, California
University of California- Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Mersedeh Bahr Hosseini, MD    310-794-6379    mbahrhosseini@mednet.ucla.edu   
Contact: Jeffrey L Saver, MD    310-794-6379    jsaver@mednet.ucla.edu   
Sponsors and Collaborators
University of California, Los Angeles
The City College of New York
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Responsible Party: Mersedeh Bahr Hosseini, MD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT04061577    
Other Study ID Numbers: 19-000529
First Posted: August 20, 2019    Key Record Dates
Last Update Posted: November 9, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Mersedeh Bahr Hosseini, MD, University of California, Los Angeles:
Transcranial direct current stimulation
Bridging neuroprotection
Adjunctive neuroprotection
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases