Low-Frequency REpetitive TRanscranial Magnetic Stimulation in ACute Ischemic StrokE Within 48 Hours

Study Overview
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Brief Summary
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This is a multicenter, open-label, evaluator-blinded, investigator-initiated, randomized clinical trial, to evaluate the clinical efficacy and safety of LF-rTMS in reducing infarct size, reducing disability rate and improving functional outcome in patients with acute ischemic stroke within 48 hours after stroke onset.

Detailed Description
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The target population of this study was patients with clinically diagnosed AIS who had an acute occlusion of the responsible vessel in the anterior circulation and were not scheduled for intravenous thrombolysis and/or endovascular therapy, the time from stroke onset to the start of study intervention was less than 48-hours. Enrolled patients were randomly assigned in a 1:1 ratio to either theLF-rTMS group or theControl group to receive: LF-rTMS group: H 4 Coil (stimulation site: prefrontal cortex, insular lobe),1-Hz rTMS, stimulation intensity RMT 100%,1200 pulses/session, two sessions (2400 pulses)/day (interval ≥2 hours), lasting about half an hour each time, the total duration of treatment was 3 days (6 sessions,7200 pulses). Control group: received routine treatment. All the above therapeutic interventions were conducted by trained TMS operators. Except for the study intervention, the subjects in both groups received clinical routine diagnosis and treatment which were not affected by the intervention. All patients were followed up until the 90th day after randomization to evaluate the clinical efficacy and safety of LF-rTMS in reducing infarct size, reducing disability rate and improving functional outcome in patients with acute ischemic stroke within 48 hours after stroke onset.

Official Title
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Low-Frequency REpetitive TRanscranial Magnetic Stimulation in ACute Ischemic StrokE Within 48 Hours (RETRACE-I): A Randomized, Open-label, Evaluator-blinded, Phase 2 Pilot Trial

Conditions
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Stroke, Acute, Stroke, Ischemic

Intervention / Treatment
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* Device: LF-rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years, gender is not limited; Acute ischemic stroke of anterior circulation was diagnosed clinically mRS 0-1 score before onset; 6 ≤ NIHSS ≤25 at randomization; Within 48 hours of stroke onset; No thrombolysis therapy or thrombectomy is planned; Obtain informed consent signed by the patient himself or by his legal authorized representative. Exclusion Criteria: TMS contraindications include metallic foreign bodies in the head, pacemaker, implantable drug pumps, cochlear implants, etc. Epilepsy or history of epilepsy, intracranial hypertension, tumor and other serious neurological disorders; Midline displacement and brain parenchymal mass effect seen in head CT and other images; Head CT or MRI showed bilateral acute cerebral infarction and involved insular infarction; Evidence of acute intracranial hemorrhage; A history of congenital or acquired hemorrhagic disease, coagulation factor deficiency, or thrombocytopenia disease; After blood pressure control, the systolic blood pressure was still ≥180 mmHg or the diastolic blood pressure was ≥110 mmHg; Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (EGFR) < 60 mL/min; Patients during pregnancy or lactation and within 90 days of planned pregnancy; Patients with severe mental disorders or dementia who can not cooperate with informed consent and follow-up; Patients with malignancy or severe systemic disease and expected survival of less than 90 days; Participants in other clinical intervention studies within 30 days before randomization or who were participating in other clinical intervention studies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LF-rTMS<br>H 4 Coil (stimulation site: prefrontal cortex, insular lobe),1-Hz rTMS, stimulation intensity RMT 100%,1200 pulses/session, two sessions (2400 pulses)/day (interval ≥2 hours), lasting about half an hour each time, the total duration of treatment was 3 days (6 sessions,7200 pulses). | Device: LF-rTMS<br>* H 4 Coil (stimulation site: prefrontal cortex, insular lobe),1-Hz rTMS, stimulation intensity RMT 100%,1200 pulses/session, two sessions (2400 pulses)/day (interval ≥2 hours), lasting about half an hour each time, the total duration of treatment was 3 days (6 sessions,7200 pulses).<br>|
| No Intervention: Control<br>Routine treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct growth | Infarct growth at 3 days was calculated as the absolute difference between the baseline core infarct volume and the 3 days post-randomization infarct volume. | 3 days | 
| Proportion of Early neurological improvement (ENI) | Proportion of patients with a reduction of ≥4 on the NIHSS, compared with the baseline score or an NIHSS of 0 or 1 | 3 days | 
| Symptomatic intracranial hemorrhage | The proportion of symptomatic intracranial hemorrhage | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final infarct volume | Final infarct volume | 3 days | 
| △NIHSS score | Change in NIHSS score from baseline | 3 days | 
| mRS scores of 0-1 | Proportion of patients with mRS scores of 0-1 | 90 days | 
| mRS scores of 0-2 | Proportion of patients with mRS scores of 0-2 | 90 days | 
| Barthel index of ADL | Barthel index of ADL, 0-100 (better) | 90 days | 
| EQ-5D-5L | The Health Questionnaire (EQ-5D-5L) is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from no problems through extreme problems. | 90 days | 
| Montreal Cognitive Assessment (MoCA) total score | Total score of the MoCA Performance on the MoCA (0-30; higher score indicates better performance) | 90 days | 
| Serious adverse events | The proportion of serious adverse events (SAE) | 90 days | 
| All-cause deaths | The proportion of all-cause deaths | 90 days | 
| Symptomatic intracranial hemorrhage | The incidence of symptomatic intracranial hemorrhage | 90 days | 
| Deterioration of neurological function | The incidence of deterioration of neurological function (NIHSS increase ≥4 points) | 3 days | 
| Stroke recurrence | Recurrence rate of symptomatic stroke (cerebral infarction, cerebral hemorrhage) | 90 days | 
| Adverse events (AE) | The proportion of adverse events (AE) | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, LF-rTMS, Phase 2 Pilot Trial