Back to resultsTranscranial Direct Current Stimulation as a Neuroprotection in Acute Stroke (TESSERACT)
Primary Purpose
Stroke, Acute
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Direct Current Stimulation
Sham Stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Stroke, Acute
Eligibility Criteria
Inclusion criteria:
- New focal neurologic deficit consistent with AIS
- NIHSS≥4 or NIHSS <4 in the presence of disabling deficits
- Age>18;
- Presence of any cortical vessel occlusion including ICA, branches of MCA, Anterior Cerebral artery (ACA), Posterior Cerebral artery (PCA), Posterior-Inferior cerebellar artery (PICA);
- Presence of salvageable penumbra with Tmax> 6 sec/ ischemic core volume (ADC < 620 μm2/s or rCBF< 30%) ≥ 1.2
- Patient ineligible for IV tPA, per national AHA/ASA Guidelines
- 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
- Acute intracranial hemorrhage
- Evidence of a large Ischemic core volume (ADC < 620 μm2/s or rCBF< 30%) ≥ 100
- Presence of tDCS contraindications - electrically or magnetically activated intracranial metal and non-metal implants.
- Severe MR contrast allergy or renal dysfunction with eGFR<30ml/min, precluding MRI gadolinium or CT iodine contrast
- Pregnancy
- Signs or symptoms of acute myocardial infarction, including EKG findings, on admission
- Suspicion of aortic dissection on admission
- 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 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
Active Comparator
Sham Comparator
Arm Label
Transcranial Direct Current Stimulation
Sham Stimulation
Arm Description
Transcranial Direct Current Stimulation
Sham Stimulation
Outcomes
Primary Outcome Measures
Safety Outcome: Rate of Symptomatic Intracranial Hemorrhage (SICH) in the Active Treatment Arms Compared to Sham Arm
The presence of SICH will be assessed on 24-hour post-stimulation scan. SICH will be defined as an intracranial parenchymal hemorrhage, subarachnoid hemorrhage, or intraventricular 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.
The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment.
Feasibility Outcome: Speed With Which HD C-tDCS Was Implemented
The median time from enrollment to HD C-tDCS initiation in the last 4 enrolled patients included three Active-Tier 2 patients and one sham.
Tolerability Outcome: Percentage of the Patients Completing the Protocol-assigned Stimulation Treatment
Percentage of the patients completing the protocol-assigned stimulation treatment
Secondary Outcome Measures
Secondary Safety Outcome: Rate of Early Neurologic Deterioration in All Active Patients Compared to Sham Arm
Early neurological deterioration will be defined as worsening ≥ 4 on NIHSS during the 24-hour period after stimulation without intracranial hemorrhage.
Secondary Safety Outcome: Rate of Mortality in All Active Patients Compared to Sham Arm,
Mortality will be defined as death or modified Rankin Scale of 6.
Secondary Safety Outcome: Rate of All Serious Adverse Events Occured During the 90 Days of Study Participation in All Active Patients Compared to Sham.
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.
Full Information
NCT ID
NCT03574038
First Posted
May 30, 2018
Last Updated
June 7, 2023
Sponsor
University of California, Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT03574038
Brief Title
Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke
Acronym
TESSERACT
Official Title
Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
September 28, 2018 (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
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Acute
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
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Transcranial Direct Current Stimulation
Arm Type
Active Comparator
Arm Description
Transcranial Direct Current Stimulation
Arm Title
Sham Stimulation
Arm Type
Sham Comparator
Arm Description
Sham Stimulation
Intervention Type
Device
Intervention Name(s)
Transcranial Direct Current Stimulation
Other Intervention Name(s)
C-tDCS
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Sham Stimulation
Intervention Description
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 Measure Information:
Title
Safety Outcome: Rate of Symptomatic Intracranial Hemorrhage (SICH) in the Active Treatment Arms Compared to Sham Arm
Description
The presence of SICH will be assessed on 24-hour post-stimulation scan. SICH will be defined as an intracranial parenchymal hemorrhage, subarachnoid hemorrhage, or intraventricular 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.
The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment.
Time Frame
At 24-hour post-stimulation
Title
Feasibility Outcome: Speed With Which HD C-tDCS Was Implemented
Description
The median time from enrollment to HD C-tDCS initiation in the last 4 enrolled patients included three Active-Tier 2 patients and one sham.
Time Frame
Time from randomization to tDCS initiation assessed up to 30 minutes
Title
Tolerability Outcome: Percentage of the Patients Completing the Protocol-assigned Stimulation Treatment
Description
Percentage of the patients completing the protocol-assigned stimulation treatment
Time Frame
After 20 minutes of stimulation period
Secondary Outcome Measure Information:
Title
Secondary Safety Outcome: Rate of Early Neurologic Deterioration in All Active Patients Compared to Sham Arm
Description
Early neurological deterioration will be defined as worsening ≥ 4 on NIHSS during the 24-hour period after stimulation without intracranial hemorrhage.
Time Frame
During the 24-hour post-stimulation
Title
Secondary Safety Outcome: Rate of Mortality in All Active Patients Compared to Sham Arm,
Description
Mortality will be defined as death or modified Rankin Scale of 6.
Time Frame
By day 90 post stimulation
Title
Secondary Safety Outcome: Rate of All Serious Adverse Events Occured During the 90 Days of Study Participation in All Active Patients Compared to Sham.
Description
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.
Time Frame
By day 90 post-stimulation
Other Pre-specified Outcome Measures:
Title
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.
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 measured: 1) Final penumbra salvage proportion, 2) Final hypoperfusion lesion reduction, 3) Early relative quantitative cerebral blood volume (qrCBV) enhancement.
Time Frame
At 2-hour and 24-hour post-stimulation
Title
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.
Description
Rate of modified Rankin Scale (mRS) of 0-2
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
NIHSS≥4 or NIHSS <4 in the presence of disabling deficits
Age>18;
Presence of any cortical vessel occlusion including ICA, branches of MCA, Anterior Cerebral artery (ACA), Posterior Cerebral artery (PCA), Posterior-Inferior cerebellar artery (PICA);
Presence of salvageable penumbra with Tmax> 6 sec/ ischemic core volume (ADC < 620 μm2/s or rCBF< 30%) ≥ 1.2
Patient ineligible for IV tPA, per national AHA/ASA Guidelines
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
Acute intracranial hemorrhage
Evidence of a large Ischemic core volume (ADC < 620 μm2/s or rCBF< 30%) ≥ 100
Presence of tDCS contraindications - electrically or magnetically activated intracranial metal and non-metal implants.
Severe MR contrast allergy or renal dysfunction with eGFR<30ml/min, precluding MRI gadolinium or CT iodine contrast
Pregnancy
Signs or symptoms of acute myocardial infarction, including EKG findings, on admission
Suspicion of aortic dissection on admission
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 platelet count of ≤ 100, INR ≥ 3, PTT ≥ 90.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mersedeh Bahr Hosseini, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
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
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Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke
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