Low-Frequency REpetitive TRanscranial Magnetic Stimulation in ACute Ischemic StrokE Within 48 Hours (RETRACE-I)

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic; Stroke, Acute
• Intervention / Treatment: Device: LF-rTMS

Detailed Description

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 the"LF-rTMS group" or the"Control group" to receive:

1. 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).
2. 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Beijing Tian tan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80 years, gender is not limited;
2. Acute ischemic stroke of anterior circulation was diagnosed clinically
3. mRS 0-1 score before onset;
4. 6 ≤ NIHSS ≤25 at randomization;
5. Within 48 hours of stroke onset;
6. No thrombolysis therapy or thrombectomy is planned;
7. Obtain informed consent signed by the patient himself or by his legal authorized representative.

Exclusion Criteria:

1. TMS contraindications include metallic foreign bodies in the head, pacemaker, implantable drug pumps, cochlear implants, etc.
2. Epilepsy or history of epilepsy, intracranial hypertension, tumor and other serious neurological disorders;
3. Midline displacement and brain parenchymal mass effect seen in head CT and other images;
4. Head CT or MRI showed bilateral acute cerebral infarction, brainstem infarction, or insular infarction;
5. Evidence of acute intracranial hemorrhage;
6. A history of congenital or acquired hemorrhagic disease, coagulation factor deficiency, or thrombocytopenia disease;
7. After blood pressure control, the systolic blood pressure was still ≥180 mmHg or the diastolic blood pressure was ≥110 mmHg;
8. Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (EGFR) < 60 mL/min;
9. Patients during pregnancy or lactation and within 90 days of planned pregnancy;
10. Patients with severe mental disorders or dementia who can not cooperate with informed consent and follow-up;
11. Patients with malignancy or severe systemic disease and expected survival of less than 90 days;
12. Participants in other clinical intervention studies within 30 days before randomization or who were participating in other clinical intervention studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LF-rTMS; 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; 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).
No Intervention: Control; Routine treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic intracranial hemorrhage	The proportion of symptomatic intracranial hemorrhage	3 days
Infarct growth from baseline to Day 3 (mL)	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. Positive values indicate infarct growth.	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
All-cause deaths	The proportion of all-cause deaths	90 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
Barthel index of ADL	Barthel index of ADL, 0-100 (better)	90 days
Serious adverse events	The proportion of serious adverse events (SAE)	90 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
Final infarct volume at Day 3 (mL)	Final infarct volume, in milliliters, measured 3 days after randomization.	3 days
Change in NIHSS score from baseline to Day 3	Change in NIHSS score from baseline to Day 3	3 days
Proportion of participants with modified Rankin Scale score 0 to 1 at Day 90	Proportion of participants with modified Rankin Scale score 0 to 1 at Day 90	90 days
Proportion of participants with modified Rankin Scale score 0 to 2 at Day 90	Proportion of participants with modified Rankin Scale score 0 to 2 at Day 90	90 days
Number of participants with neurological deterioration within 3 days	The incidence of deterioration of neurological function (NIHSS increase ≥4 points)	3 days
Number of participants with symptomatic intracranial hemorrhage within 90 days	Number of participants with symptomatic intracranial hemorrhage within 90 days	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting-state functional connectivity in the insular-prefrontal circuit.	Change in resting-state functional connectivity in the insular-prefrontal circuit.	90 days
Change in peripheral immune biomarker levels from baseline to Day 3	Change in peripheral immune biomarker levels from baseline to Day 3	3 days
Change in peripheral immune biomarker levels from baseline to Day 7	Change in peripheral immune biomarker levels from baseline to Day 7	7 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yongjun Wang, MD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2024
• Primary Completion (Actual): July 28, 2025
• Study Completion (Actual): October 25, 2025

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; LF-rTMS; Phase 2 Pilot Trial
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke
• Other Study ID Numbers: HX-A-2023001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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