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Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke (TESSERACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03574038
Recruitment Status : Terminated (Interim Analysis)
First Posted : June 29, 2018
Last Update Posted : April 18, 2022
Sponsor:
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 who are ineligible for intravenous thrombolysis and endovascular therapy.

Condition or disease Intervention/treatment Phase
Stroke, Acute Device: Transcranial Direct Current Stimulation Other: Sham Stimulation 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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Traditional 3+3 (rule-based, modified Fibonacci) dose escalation design
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial
Actual Study Start Date : September 28, 2018
Actual Primary Completion Date : April 1, 2022
Actual Study Completion Date : April 1, 2022

Arm Intervention/treatment
Active Comparator: Transcranial Direct Current Stimulation
Transcranial Direct Current Stimulation
Device: Transcranial Direct Current Stimulation
Patients will be randomized to active treatment (C-tDCS) vs sham stimulation in a 3:1 ratio. There will be 6 dose tiers, reflecting increasing intensity and duration of stimulation: Tier 1 - 1 mA, single 20 - min cycle; Tier 2- 2 mA, single 20 min cycle; Tier 3 - 1 mA, 2 cycles of 20 min/20 min off; Tier 4- 2 mA, 2 cycles of 20 min/20 min off; Tier 5 - 1 mA, 3 cycles of 20 min/20 min off; Tier 6 - 2 mA, 3 cycles of 20 min/20 min off.
Other Name: C-tDCS

Sham Comparator: Sham Stimulation
Sham Stimulation
Other: Sham Stimulation
Patients will be randomized to active treatment (C-tDCS) vs sham stimulation in a 3:1 ratio. Patients in the sham stimulation arm at all the tiers will have the cap and electrodes in place, and sham switch moved but without prolonged delivery of electrical stimulation.




Primary Outcome Measures :
  1. Primary safety outcome: the rate of symptomatic intracranial hemorrhage (SICH) in the active treatment arm compared to sham arm, and between higher and lower dose tiers. [ Time Frame: At 24-hour post-stimulation ]
    The presence of SICH will be assessed on 24-hour post-stimulation scan. SICH will be defined as an intracranial hemorrhage with an increase of 4 or more points on the National Institute of Health Stroke Scale (NIHSS) within 24 hours of stimulation.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of SICH compared to sham.


Secondary Outcome Measures :
  1. Secondary safety outcome: The rate of asymptomatic intracranial hemorrhage (AICH) in the active treatment arm compared to sham arm, and between higher and lower dose tiers. [ Time Frame: At 24-hour post-stimulation ]
    The AICH will be defined as an intracranial hemorrhage on 24-hour scan that is not associated with NIHSS worsening ≥ 4.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of AICH compared to sham.

  2. Secondary safety outcome: the rate of early neurologic deterioration in the active treatment arm compared to sham arm, and between higher and lower dose tiers. [ Time Frame: During the 24-hour post-stimulation ]
    Early neurological deterioration will be defined as worsening ≥ 4 on NIHSS during the 24-hour period after stimulation without intracranial hemorrhage.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of early neurological detorioration compared to sham.

  3. Secondary safety outcome: the rate of mortality in the active treatment arm compare to sham arm, and between higher and lower dose tiers. [ Time Frame: By day 90 post stimulation ]
    Mortality will be defined as death or modified Rankin Scale of 6. The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of mortality compared to sham.

  4. Secondary safety outcome: the rate of all serious adverse events occurring during the 90 days of study participation in the active treatment arm compare to sham arm, and between higher and lower dose tiers. [ Time Frame: By day 90 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. The rate of serious adverse events will be compared between the active treatment and sham patients, and between higher and lower dose tiers.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of serious adverse events compared to sham.


Other Outcome Measures:
  1. Tolerability Outcome: the percentage of the patients completing the protocol-assigned stimulation treatment and secondarily, the rate and severity of cutaneous, neurologic, nociceptive or other adverse effects will be assessed. [ Time Frame: After 20 minutes of stimulation period ]
    A patient will be considered to have tolerated the stimulation if at least 75% of the stimulation period is completed. The treatment will be considered generally tolerable if, among all enrolled patients, tolerated procedures are achieved in ≥90% of patients without early cessation. At the end of each 20-minute stimulation session, a tolerability form will be completed based on validated cutaneous, neurological, and pain items of the PRO-CTAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). A separate tolerability form will be completed by the patient at the end of each stimulation cycle (20 minutes).

  2. Feasibility Outcome: the speed with which tDCS will be implemented. [ Time Frame: Median time from randomization to tDCS initiation ≤ 10 minutes ]
    The predefined success threshold for feasibility will be median time from randomization to tDCS initiation ≤ 10 minutes in the last 10 enrolled patients.

  3. Exploratory Imaging Efficacy Outcome: examining the imaging biomarkers, including penumbral salvage, collateral enhancement, and infarct growth. [ Time Frame: At 2-hour and 24-hour post-stimulation ]

    By comparing the baseline MR/CT imaging with the MR/CT imaging at 2-hour (early) and 24-hour (late) post-stimulation the following will be measured: 1) Early and late penumbra preservation: Volume of baseline penumbra tissue not progressing to ischemic core at 2h and 24h; 2) Early and late collateral flow enhancement: Perfusion lesion volume at baseline - Perfusion lesion volume at 2h and 24h. 3) Early and final infarct growth: Ischemic core lesion volume at 2h and 24h - Ischemic core lesion volume at baseline.

    Imaging efficacy endpoints will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in penumbral salvage, collateral enhancement, or lower infarct growth compared to sham.


  4. Exploratory Clinical Efficacy Outcome: examining the clinical outcomes of early neurologic deficit evolution, and 3-month global disability and health-related quality of life. [ Time Frame: At day 90 post stimulation ]

    Four clinical outcome measures will be assessed at 90 days: the modified Rankin Scale (mRS), a rating of global disability; the Barthel Index (BI), a measure of instrumental activities of daily living; the National Institutes of Health Stroke Scale (NIHSS), a measure of neurologic deficit severity; and the EuroQol (EQ-5D), an assessment of health-related quality of life; and AMC Linear Disability Scale, a granular degree of disability.

    Clinical efficacy endpoints will be characterized in the active and sham patients, and in higher and lower dose tiers.The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in an improved clinical outcome compared to sham.




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:

  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.

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): NCT03574038


Locations
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United States, California
University of California- Los Angeles (UCLA)
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Investigators
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Principal Investigator: Mersedeh Bahr Hosseini, MD University of California, Los Angeles
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Responsible Party: Mersedeh Bahr Hosseini, MD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03574038    
Other Study ID Numbers: 18-000421
First Posted: June 29, 2018    Key Record Dates
Last Update Posted: April 18, 2022
Last Verified: April 2022

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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
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases