Transcranial Direct Current Stimulation as a Neuroprotection in Acute Stroke

NCT03574038 | Completed Results DMC FDA Device

• 1 other identifier: 18-000421
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke, Acute

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Secondary Safety Outcome: Rate of Early Neurologic Deterioration in All Active Patients Compared to Sham Arm

  During the 24-hour post-stimulation

• Secondary Safety Outcome: Rate of Mortality in All Active Patients Compared to Sham Arm,

  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.

  By day 90 post-stimulation

Other Outcomes (2)

• 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.

  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.

  At day 90 post stimulation

Study Arms (2)

Transcranial Direct Current Stimulation

ACTIVE COMPARATOR

Transcranial Direct Current Stimulation

Device: Transcranial Direct Current Stimulation

Sham Stimulation

SHAM COMPARATOR

Sham Stimulation

Other: Sham Stimulation

Interventions

Transcranial Direct Current Stimulation DEVICE

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.

Also known as: C-tDCS

Transcranial Direct Current Stimulation

Sham Stimulation OTHER

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.

Sham Stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• \) A signed informed consent is obtained from the patient or patient's legally authorized representative

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California- Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Bahr-Hosseini M, Nael K, Unal G, Iacoboni M, Liebeskind DS, Bikson M, Saver JL; TESSERACT Trial Group. High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Netw Open. 2023 Jun 1;6(6):e2319231. doi: 10.1001/jamanetworkopen.2023.19231.

  PMID: 37342040 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Dr. Mersedeh Bahr-Hosseini
• Organization: Study's principal investigator

MBahrHosseini@mednet.ucla.edu

3107941195

Study Officials

• Mersedeh Bahr Hosseini, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Traditional 3+3 (rule-based, modified Fibonacci) dose escalation design

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: June 29, 2018
• Study Start: September 28, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: June 27, 2023
• Results First Posted: June 8, 2023

Record last verified: 2023-06

Locations

US (1)