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

Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Stroke, Acute
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation; Other: Sham Stimulation

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• 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:

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: 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.
Active Comparator: 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 Names: C-tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 24-hour post-stimulation
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.	Time from randomization to tDCS initiation assessed up to 30 minutes
Tolerability Outcome: Percentage of the Patients Completing the Protocol-assigned Stimulation Treatment	Percentage of the patients completing the protocol-assigned stimulation treatment	After 20 minutes of stimulation period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During the 24-hour post-stimulation
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.	By day 90 post stimulation
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.	By day 90 post-stimulation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	At 2-hour and 24-hour post-stimulation
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.	Rate of modified Rankin Scale (mRS) of 0-2	At day 90 post stimulation

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Mersedeh Bahr Hosseini, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: May 30, 2018
• First Submitted That Met QC Criteria: June 27, 2018
• First Posted (Actual): June 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 18-000421

Drug and device information, study documents

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