Clinical trial NCT04801446: Transcranial Direct Current Stimulation in Acute Ischemic Stroke Treatment
Official title: Transcranial Direct Current Stimulation in Acute Ischemic Stroke Treatment - Safety and Feasibility Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Keywords: stroke
transcranial direct current stimulation
tDCS
neuroprotection
Lead sponsor: General University Hospital, Prague
Sponsor class: OTHER
First posted: 2021-03-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Traditional 3+3 (rule-based, modified Fibonacci) dose escalation design
Primary purpose: TREATMENT

Brief summary: This prospective interventional single center randomized sham controlled dose-escalation study will assess safety, tolerability, feasibility and potential efficacy of transcranial direct current stimulation (tDCS) in acute stroke patients with substantial salvageable penumbra due to a large vessel occlusion who are ineligible for endovascular therapy (EVT). Patients will be randomized in a 3:1 design, to cathodal versus sham (control) tDCS, 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.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years.
* New focal neurologic deficit consistent with acute ischemic stroke.
* Baseline NIHSS ≥ 4 or NIHSS \< 4 in the presence of disabling deficits (e.g. aphasia)
* Presence of acute occlusion of ICA or MCA (including MCA peripheral cortical branches) according to clinical picture and baseline CTA/CTP scan.
* Presence of salvageable penumbra with Tmax \> 6 sec/ ischemic core volume (rCBF \< 30%) ≥ 1.2 on baseline CTP scan.
* Patient is ineligible for EVT per current national guidelines (Cerebrovascular Section of Czech Neurological Society ČLS JEP).
* 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 (point 30 of Declaration of Helsinki).

Exclusion Criteria:

* Acute intracranial hemorrhage including suspected subarachnoid hemorrhage.
* Other than ischemic cause of acute neurological deficit (stroke mimics:postparoxysmal Todd´s palsy, metabolic cause, tumor, meningoencephalitis etc.).
* Evidence of a large Ischemic core volume on baseline CTP: volume of rCBF\<30% ≥ 100ml.
* Subacute or chronic subdural hematoma or hygroma.
* Intra-axial malignant brain tumor.
* History of spontaneous ICH in the past.
* History of seizure disorder or new seizures with presentation of current stroke.
* History of intracranial surgery.
* Presence of tDCS contraindications: skin lesion at the site of stimulation (open wound, acute inflammation of skin or subcutaneous tissue, burns etc.); skull defect at the site of stimulation (e.g. skull fracture, postcraniectomy); implanted electric device (pacemaker, ICD, DBS, cochlear implant etc.); presence of metal material in head (e.g. metal stent, clamps etc.).
* Thrombocytopenia \< 100 000/ul.
* INR \> 3,0.
* Heparin or LMWH therapy in last 48 hours with aPTT increased more than 1,5 times over limit of the laboratory.
* History of acute overdose by DOAC.
* Known congenital or acquired increased bleeding propensity.
* Suspected or confirmed pregnancy.
* Known CT iodine contrast allergy.
* Known renal dysfunction (eGFR\<30 ml/min.).
* Signs or symptoms of acute myocardial infarction, including ECG findings, on admission.
* Suspicion of aortic dissection on admission.
* 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.

Primary outcomes:
measure: 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.
timeFrame: At 24-hour post-stimulation
Secondary outcomes:
measure: 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.
timeFrame: At 24-hour post-stimulation
measure: 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.
timeFrame: During the 24-hour post-stimulation
measure: Secondary safety outcome: the rate of mortality in the active treatment arm compare to sham arm, and between higher and lower dose tiers.
timeFrame: By day 90 post stimulation
measure: 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.
timeFrame: By day 90 post-stimulation
Other outcomes:
measure: Tolerability outcome: percentage of the patients completing the stimulation
timeFrame: During procedure
measure: Tolerability outcome: rate and severity of cutaneous, neurological, nociceptive and other adverse effects
timeFrame: During procedure
measure: Feasibility outcome
timeFrame: During procedure
measure: Exploratory imaging efficacy outcome: final infarct growth
timeFrame: At 24-hour post-stimulation
measure: Exploratory clinical efficacy outcome: neurological deficit
timeFrame: At 24-hour post-stimulation and at day 90 post-stimulation
measure: Exploratory clinical efficacy outcome: global disability
timeFrame: At day 90 post-stimulation
measure: Exploratory clinical efficacy outcome: instrumental activities of daily living
timeFrame: At day 90 post-stimulation
measure: Exploratory clinical efficacy outcome: health-related quality of life
timeFrame: At day 90 post-stimulation
measure: Exploratory clinical efficacy outcome: granular degree of disability
timeFrame: At day 90 post-stimulation
Locations:
city: Prague
country: Czechia
facility: Department of Neurology, General University Hospital in Prague
Study officials:
References: