Brain-Oscillation-Synchronized Stimulation to Enhance Motor Recovery in Early Subacute Stroke

Not Applicable

Recruiting

• Conditions: Ischemic Stroke, Acute
• Interventions: Device: Bossdevice

• Registration Number: NCT05600374
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

We will investigate the therapeutic efficacy of EEG-synchronized noninvasive repetitive transcranial magnetic stimulation (rTMS) in the early subacute phase after ischemic stroke to improve upper limb motor rehabilitation. We hypothesize that synchronization of rTMS with the phase of the ongoing sensorimotor oscillation indicating high corticospinal excitability leads to significantly stronger improvement of paretic upper limb motor function than the same rTMS protocol non-synchronized to the ongoing sensorimotor oscillation or sham stimulation.

Detailed Description

High-frequency rTMS will be applied to the ipsilesional motor cortex in 400 bursts of 100 Hz triplets with a mean inter-burst interval of 3 s (20 min treatment duration, 1,200 pulses per day) for 5 consecutive workdays (6,000 pulses total) at a stimulus intensity of 80% of resting motor threshold, in one of three conditions/arms, followed by 40 min task-specific hand/arm-physiotherapy.

Study Timeline

• Study First Submitted: 2022-10-21
• Study First Submitted QC: 2022-10-26
• Study First Posted: 2022-10-31
• Study Start: 2023-02-06
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-22
• Primary Completion: 2025-05-31
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

Subjects meeting all of the following criteria will be considered for admission to the trial:

1. Age ≥ 18 years at the time of signing the informed consent.

2. Cerebral ischemia identified by brain imaging (cerebral MRI or CT) occurred 1-14 days ago.

3. Subject understands and voluntarily signs an informed consent document prior to any study related assessments/procedures.

4. Stroke has resulted in a new arm-/hand motor deficit with ≤ 50 points in the FMA-UE.

5. Presence of motor evoked potentials (MEPs) in the paretic hand. MEPs has to be obtained in the resting muscle

   o If no MEPs can be obtained, MEP search procedure can be repeated later up to 14 days after stroke onset.

6. ● μ-oscillation (8-12 Hz) is recordable by EEG in the ipsilesional sensorimotor cortex with a sufficient signal-to-noise ratio of at least 3 dB

7. ● Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria

Subjects presenting with any of the following criteria will not be included in the trial:

1. Hemorrhagic stroke (this refers to primary intracerebral hemorrhage only; hemorrhagic transformation of ischemic infarcts is not an exclusion criterion)
2. Estimated life expectancy < 12 months
3. Presence of intracranial ferromagnetic metal (extracranial stents ≥10 cm away from the TMS coil are acceptable) in accordance with current safety guidelines [18]
4. Intraocular metal, cochlear implants
5. If TMS might interact with sensors of active implants (e.g., intra-cardiac defibrillators).
6. If a cranial bone gap affects currents induced by TMS (such as after craniotomy).
7. History of seizures or epilepsy.
8. Treatment intervention can't be started within 14 days after onset of stroke.
9. Women during pregnancy and lactation.
10. Participation in other studies if they are MDR or AMG studies or there is otherwise a high risk of insurance law issues intervening between two studies. In case of uncertainty, competing insurances must be contacted prior to participation
11. persistent addiction disorder (except for nicotine dependence)
12. CNS malignoma
13. If there is any concern by the investigator regarding the safe participation of the subject in the study or for any other reason the investigator considers the subject inappropriate for participation in the study.
14. The ability to consent for patients who are unable to speak will be assessed on the basis of the NIHS-Score by an independent physician (details see chapter 21 and appendix).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Personalized stimulation	Bossdevice	Each 100 Hz triplet is triggered when a real-time analyzed EEG-defined state of high corticospinal excitability is detected (i.e., the negative peak of the ongoing sensorimotor \~10 Hz μ-oscillation).

Primary Outcome Measures

Name	Time	Method
Motor performance after the intervention	After the last treatment session (5 days after first treatment)	Primary efficacy endpoint is the motor performance after the intervention, as assessed by the Fugl-Meyer assessment (FMA-UE, range 0-66, 0 = no motor function, 66 = normal motor function) of the upper extremity (FMA-UE). The upper-extremity (UE) portion of the Fugl-Meyer assessment is the most frequently used scale to quantify post-stroke motor recovery of the upper extremity. The FMA-UE was used as an endpoint in most of the recent high-frequency rTMS trials in early subacute stroke patients.

Secondary Outcome Measures

Name	Time	Method
Barthel Index	At screening and after 3 months after treatment	Barthel Index (ordinary scale ordinal scale 0-100, 0 = fully dependent, 100 =independent in feeding, walking and grooming)
modified Rankin Scale Score	At screening and after 3 months after treatment	Rankin Scale Score (range 0-6, 0 = no disability, 6 =death)
Motor performance after 3 months	3 months after the intervention	Motor performance 3 months after the intervention, as assessed by the FMA-UE
inpatient/npatient rehabilitation	At screening and after 3 months after treatment	* Number of days as an inpatient (in days); * Number of days in inpatient rehabilitation (in days)
Assessment to measure quality of life	At screening and after 3 months after treatment	Stroke-Specific Quality-of-Life Scale (SS-QOL)
grip strength	At screening and after 3 months after treatment	Relative grip strength measured with a vigorimeter (measured in kg).

Trial Locations

Locations (7)

Universitätsklinikum Frankfurt, Zentrum der Neurologie und Neurochirurgie; 🇩🇪 Frankfurt a.M., Germany

Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie; 🇩🇪 Greifswald, Germany

Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie; 🇩🇪 Mainz, Germany

Uniklinik Köln, Klinik und Poliklinik für Neurologie; 🇩🇪 Köln, Germany

Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie; 🇩🇪 Leipzig, Germany

Universitätsklinikum Tübingen, Klinik für Neurologie; 🇩🇪 Tübingen, Germany

Universitätsklinikum Münster, Klinik für Allgemeine Neurologie; 🇩🇪 Münster, Germany